740 research outputs found

    Spillover and diffraction sidelobe contamination in a double-shielded experiment for mapping Galactic synchrotron emission

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    We have analyzed observations from a radioastronomical experiment to survey the sky at decimetric wavelengths along with feed pattern measurements in order to account for the level of ground contamination entering the sidelobes. A major asset of the experiment is the use of a wire mesh fence around the rim-halo shielded antenna with the purpose of levelling out and reducing this source of stray radiation for zenith-centered 1-rpm circular scans. We investigate the shielding performance of the experiment by means of a geometric diffraction model in order to predict the level of the spillover and diffraction sidelobes in the direction of the ground. Using 408 MHz and 1465 MHz feed measurements, the model shows how a weakly-diffracting and unshielded antenna configuration becomes strongly-diffracting and double-shielded as far-field diffraction effects give way to near-field ones. Due to the asymmetric response of the feeds, the orientation of their radiation fields with respect to the secondary must be known a priori before comparing model predictions with observational data. By adjusting the attenuation coefficient of the wire mesh the model is able to reproduce the amount of differential ground pick-up observed during test measurements at 1465 MHz.Comment: 14 pages, 17 eps + 1 gif figures and 4 Tables. Accepted for publication in A&AS. Fig.7 available at full resolution from http://www.das.inpe.br/~tello/publications.ht

    Immunoglobulin Production Pattern in Allergic and Non-Allergic Subjects:

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    Allergic rhinitis (AR) is characterized by Th2 polarized immune response, such as increased IL-4 and reduced IFN-Îł production, and by a functional defect of T regulatory cells. This impaired immune response profile influences the pattern of immunoglobulin (Ig) production in allergic patients. However, no studies have compared the pattern of inhalant allergen-specific Ig classes between allergic patients and normal subjects. The aim of this study is to therefore investigate the allergen-specific IgE, IgG, IgG4, and IgA serum level pattern in a group of patients with pollen allergy and in non-allergic healthy subjects. One hundred and two allergic patients (evaluated both out of and in the pollen season) were enrolled. In addition, 50 healthy non-allergic subjects were recruited during the whole year. Serum allergen-specific IgE, IgG, IgG4, and IgA for Parietaria, grasses, and birch were quantitatively determined by the ImmunoCAP System method. Allergen-specific IgE, IgG, IgG4, and IgA serum levels were significantly different for each tested allergen (p=0.0001 for each class) among groups. Allergic patients, mainly during pollen season, showed the highest IgG, IgG4, and IgA levels. The present study therefore provides the preliminary evidence that Ig production pattern toward inhalant allergens may depend on the specificity of the allergenic response both in non-allergic subjects and allergic patients Allergic patients do not show a defect of IgG and IgA classes. In addition, this study is the first that quantitatively evaluates the Ig classes. However, further studies should include non-allergic subjects evaluated both during and out of the pollen season

    SWIRP (Submm-Wave and Long Wave InfraRed Polarimeter); Development and Characterization of a Sub-Mm Polarimeter for Ice Cloud Investigations

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    A major source of uncertainty in climate models is the presence, shape and distribution of ice particles in the uppermost layers of the clouds. The effects of this component are poorly constrained, turning ice particles into an almost-free variable in many climate models.NASA-GSFC is developing a new instrument aimed at measuring the size and shape of ice particles. The instrument consists of two sub-mm polarimeters (at 220 and 670 GHz) coupled with a long-wave infrared polarimeter at 10 micron. Each polarimeter has identical V-pol and H-pol channels; the axes of polarization are defined geometrically by the orientation of the waveguide elements, and the purity has been measured in the lab. The instrument is configured as a conical scanner, suitable for deployment as a payload on a small satellite or on a high-altitude sub-orbital platform. From a 400 km orbit, the instrument has a 3dB spatial resolution of 20 (10) km at 220 (670) GHz and a swath of 600 km over 180 degrees of view.The BAPTA (Bearing And Power Transfer Assembly) carries heritage from the SSMIS design, now in its 22nd year of on-orbit operation, but with a much reduced SWaP (Size Weight and Power) footprint, suitable for a small satellite.The main components of the instrument have been fabricated and are undergoing final testing prior to their integration as a single unit. The sub-mm channels have dedicated secondary reflectors which illuminate a shared primary reflector. The receiving units are placed behind the focal point of the optical arrangement, so that all beams equally illuminate the primary reflector and are almost co-located on the ground (within a single 220 GHz footprint). Primary and secondary beam patterns have been measured and verified to match the as-designed expectations. A Zytex (TM) window is deployed to protect the secondary reflectors and the feed horns from debris and other contaminants, and to reduce the heat load from the active (hot) IR calibration unit. The insertion loss of Zytex has been measured and is accounted in the calibration equation of the sub-mm channels.The radiometric performance of the sub-mm receivers has been characterized in the lab and under operational conditions of temperature and pressure.This paper discusses the design constraints on the sub-mm components, details of the scientific goals and their flowdown, and describes the characterization of the polarimeters. Options to optimize the layout and distribution of the masses within the assembly, with the goal of making the instrument even more compact and fully-compatible with cubesat-class satellites will be presented

    Novel Bifunctional Compounds Targeting Nicotine and Dopamine Receptor Subtypes: Synthesis and Pharmacological Investigation

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    Future therapies for diseases associated with altered dopaminergic signaling, including Parkinson\u2019s disease, schizophrenia and drug addiction or drug dependence, may be substantially built on the existence of intramembrane receptor-receptor interactions within receptor mosaics where it is believed that the D2 receptor may operate as the \u201chub receptor\u201d [1]. In particular, it has been proposed that striatal dopaminergic neurotransmission could be under the control of receptor heteromers containing D2 autoreceptors and non-alpha7 nicotinic acetylcholine heteroreceptors [2]. In an attempt to investigate the biochemical and functional interactions between dopaminergic autoreceptors and nAChRs containing the beta2 subunit, we designed and prepared a group of potential bifunctional derivatives incorporating a D2/D3 agonist moiety and a nicotinic alpha4beta2 antagonist fragment, linked by polymethylene spacers of different length. The new compounds have been biologically characterized for their affinity/specificity/functional profile at the target nACh and D2 receptor subtypes. The synthesis of the designed derivatives and the results of their pharmacological investigation will be presented and discussed. [1] K.Fuxe, D.Marcellino, A.Rivera, Z.Diaz-Cabiale, M.Filip, B.Gago, D.C.S.Roberts, U.Langel, S.Genedani, L.Ferraro, A.de la Calle, J.Narvaez, S.Tanganelli, A.Woods, L.F.Agnati, Brain Res.Rev., 58, 2008, 415-452. [2] D.Quarta, F.Ciruela, K.Patkar, J.Borycz, M.Solinas, C.Lluis, R.Franco, R.A.Wise, S.R.Goldberg, B.T.Hope, A.Woods, S.Ferr\ue9, Neuropsychopharmacol., 32, 2007, 35-42

    Synthesis and application of isotope-labeled carnosine in LCMS/MS

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    Carnosine is an endogenous dipeptide, composed of \u3b2-alanine and L-histidine, and is highly concentrated in skeletal muscle and other excitable tissues. Its physiological roles, based on its biochemical properties, include pH-buffering, metal-ion chelation and antioxidant capacity as well as the ability to protect against the formation of advanced glycation and lipoxidation end-products.1 For these reasons, besides its nutritional ergogenic application in the sport community,2 carnosine supplementation offers a therapeutic potential for the treatment of numerous diseases in which ischemic or oxidative stress is involved.1 Quantitation of carnosine in biological matrices appears to be crucial for these applications, and LC-MS procedures with isotope-labeled internal standards are the state-of-the-art approach for this analytical need.3 The use of these standards allows to account for variations during the complex sample preparation process, different matrix effects between patient samples, and variations in instrument performance. Figure 1 In this work, we present a fast and highly efficient synthetic route to obtain a deuterated carnosine analogue (Figure 1) starting from the trideuterated L-histidine (\u3b1-d1, imidazole-2,5-d2). Moreover, the use of Carnosine-d3 in the validation of a multiple reaction monitoring (MRM) LC-MS/MS method for the analytical quantitation of carnosine in a biological matrix will be reported. References 1. Boldyrev, A. A.; Aldini, G.; Derave, W. Physiol. Rev. 2013, 93, 1803\u20131845. 2. Brisola, G.; Zagatto, A. J. Strength Cond. Res. 2019, 33, 253-282. 3. Stokvis, E.; Rosing, H.; L\uf3pez-L\ue1zaro, L.; Schellens, J. H. M.; Beijnen, J. H. Biomed. Chromatogr. 2004, 18, 400-402

    Peptide derivatives and therapeutic activity thereof

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    Disclosed are peptide or pseudopeptide derivatives containing a nitrogenous heterocyclic residue with blocking activity against the by-products of lipid oxidative, stress, and in particular of unsaturated aldehydes such as malondialdehyde and 4-hydroxy-trans-2-nonenal (HNE). Formula (I

    Clustering in gravitating N-body systems

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    We study gravitational clustering of mass points in three dimensions with random initial positions and periodic boundary conditions (no expansion) by numerical simulations. Correlation properties are well defined in the system and a sort of thermodynamic limit can be defined for the transient regime of cluste ring. Structure formation proceeds along two paths: (i) fluid-like evolution of density perturbations at large scales and (ii) shift of the granular (non fluid) properties from small to large scales. The latter mechanism finally dominates at all scales and it is responsible for the self-similar characteristics of the clustering.Comment: 7 pages, 3 figures. Accepted for publication in Europhys. Let

    Synthesis of a group of novel Xanomeline/77-LH-28-1 hybrid ligands and their FRET investigation at muscarinic acetylcholine receptor subtypes

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    In connection with our interest in investigating novel rationally designed bitopic (i.e., orthosteric/allosteric) derivatives targeting muscarinic acetylcholine receptor (mAChR) subtypes (1,2,3), in this study we designed and synthesized a new set of ligands that integrate in the same molecular skeleton the pharmacophoric moieties of Xanomeline and of 77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone). Xanomeline is a well-known M1/M4-preferring orthosteric agonist, which ameliorated cognitive impairments in Alzheimer\u2019s disease patients and showed activity in various models of schizophrenia, thus being potentially beneficial for treatment of positive, negative and cognitive symptoms (4). On the other hand, 77-LH-28-1 was characterized as an M1-selective, positive allosteric modulator, thus representing an interesting pharmacological tool with cognition enhancing properties (5). As illustrated below, we planned the novel bipharmacophoric derivatives as merged structures, with the tetrahydropyridine nucleus of Xanomeline as the central core. In the last years, different receptor sensors, based on the fluorescence resonance energy transfer (FRET), were generated for various G protein-coupled receptors, and represented a valuable tool to investigate real time receptor activation as well as ligand-receptor interactions. Recently, this analysis was performed also on a set of bitopic ligands designed for a selective interaction with M1 mAChRs (6). Our preliminary results on the group of Xanomeline/77-LH-28-1 hybrid compounds indicate, for the M1 sensor, a reproducible activation response, which depends on the linker length. Conversely, no FRET-related effect could be detected at the M2 sensor. Thus, a critical spacer length of the hybrid compounds induces conformational changes with a degree of selectively for the M1 muscarinic receptor. The synthesis and the results of pharmacological investigation will be presented and discussed. References: 1. J. Antony, K. Kellershohn, M. Mohr-Andr\ue4, A. Kebig, S. Prilla, M. Muth, E. Heller, T. Disingrini, C. Dallanoce et al., FASEB J 2009, 23, 442-450. 2. A. Bock, B. Chirinda, F. Krebs, R. Messerer, J. B\ue4tz, M. Muth, C. Dallanoce et al., Nat. Chem. Biol. 2014, 10, 18-20. 3. A. Bock, M. Bermudez, F. Krebs, C. Matera, B. Chirinda, D. Sydow, C. Dallanoce et al., J. Biol. Chem. 2016, 291, 16375-16389. 4. S. Barak, I. Weiner, Int. J. Neuropsychoph. 2011, 14, 1233-1246. 5. C. J. Langmead, N. E. Austin, C. L. Branch, J. T. Brown, K. A. Buchanan, C. H. Davies, I. T. Forbes et al., Br. J. Pharmacol. 2008, 154, 1104-1115. 6. R. Messerer, M. Kauk, D. Volpato, M. C. Alonso Canizal, J. Kl\uf6ckner, U. Zabel, S. Nuber, C. Hoffmann, U. Holzgrabe, ACS Chem. Biol. 2017, 12, 833-843
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