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

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

Synthesis of novel epibatidine-related derivatives through 1,3-dipolar cycloaddition of pyridinenitrile oxides

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

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

Peptide derivatives and therapeutic activity thereof

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

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

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

Response of Foraminifera to Anthropogenic Nicotine Pollution of Cigarette Butts: An Experimental Approach

The most often dispersed environmental pollutants that are released both directly and indirectly into the environment that may eventually reach aquatic ecosystems and contaminate aquatic biomes are cigarette butts (CBs). Toxicants such as nicotine, dangerous metals, total particulate matter, and recognized carcinogens can be introduced and transported via CBs into aquatic ecosystems. The examination of the effects of synthetic nicotine on three different species of cultured benthic foraminifera was the focus of this study. Three foraminiferal species from three distinct biomineralization pathways were specifically examined for viability and cellular ultrastructure, including the calcareous perforate Rosalina globularis, the calcareous imperforate Quinqueloculina spp., and the agglutinated Textularia agglutinans. The survival rate, cellular stress, and decalcification were used to assess the toxicological effects of synthetic nicotine. We were able to analyze the reaction of major macromolecules and calcium carbonate to this pollutant using FTIR (Fourier Transform Infrared) spectroscopy. High Performance Liquid Chromatography (HPLC) study was performed to increase our understanding of nicotine bioavailability in the medium culture. Different acute experiments were performed at different dates, and all indicated that synthetic nicotine is acutely hazardous to all three cultured foraminiferal taxa at lethal and sublethal concentrations. Each species responded differently depending on the type of shell biomineralization. Synthetic nicotine enhances shell decalcification and affects the composition of cytoplasmic macromolecules such as lipids and proteins, according to the FTIR spectroscopy investigations. The lipid content rose at lethal concentrations, possibly due to the creation of vesicles. The proteins signal evidences general cellular dyshomeostasis. The integration among the acute toxicity assay, synchrotron, and chemical HPLC analyses provided a valuable approach for the assessment of nicotine as a biomarker of exposure to the toxicants associated with smoking and the impact of this emerging and hazardous material on calcifying marine species

Toward the Rational Design of Lipid Gene Vectors: Shape Coupling between Lipoplex and Anionic Cellular Lipids Controls the Phase Evolution of Lipoplexes and the Efficiency of DNA Release

A viewpoint now emerging is that a critical factor in lipid-mediated transfection (lipofection) is the structural evolution of lipoplexes upon Interaction with anionic cellular lipids, resulting in DNA release At the early stages of interaction, We found a universal behavior of lipoplex/anionic lipid (AL) Mixtures the lipoplex structure is slightly perturbed, while the one-dimensional DNA lattice between cationic membranes is largely diluted by ALs This finding is in excellent agreement with previous Suggestions on the mechanism of DNA unbinding from lipoplexes by ALs Upon further interaction, the propensity of a given lipoplex structure to be solubilized by anionic cellular lipids strongly depends on the shape coupling between lipoplex and ALs Furthermore. we investigated the effect of the membrane charge density and a general correlation resulted the higher the membrane charge density of anionic membranes, the higher their ability to solubilize the structure of lipoplexes and to promote DNA release Lastly, the fort-nation of nonlamellar phases in lipoplex/AL mixtures is regulated by the propensity of anionic cellular lipids to adopt nonlamellar phases Remarkably. also phase transition rates and [DNA release were found to be strongly affected by the shape coupling between lipoplex and ALs. It thus seems likely that the structural and phase evolution of lipoplexes may only be meaningful in the context of specific anionic cellular membranes These results highlight the phase properties of the carrier lipid/cellular lipid Mixtures as a decisive factor for optimal DNA release and suggest a potential strategy for the rational design of efficient cationic lipid carrier

Design, synthesis and preliminary biological evaluation of 3-cyclopropyl-4-phenoxy-1H-pyrazole derivatives as small molecular ligands of RAGE

Receptor for advanced glycation end products (RAGE) is a multiligand receptor belonging to the immunoglobulin superfamily and plays a crucial role in the development of many human diseases such as neurodegenerative diseases, diabetes, cardiovascular diseases and cancer.1 RAGE is involved in a number of cell processes such as neuroinflammation, apoptosis, proliferation and autophagy, and therefore it is of considerable interest as a promising drug target for innovative therapeutic approaches. It consists of an extracellular region, a short hydrophobic transmembrane spanning region, and a highly charged amino acid cytoplasmatic tail. The extracellular region contains a signal peptide, followed by one N-terminal V-type immunoglobulin domain and two C-type (C1 and C2) immunoglobulin domains.2 RAGE is able to interact with a large number of pro-inflammatory and regulatory molecules, such as advanced glycation end-products (AGEs), quinolinic acid, beta amyloid (A\u3b2), high mobility group box 1 (HMGB1), S100/calgranulin family proteins.3,4 However, due to the structural heterogeneity of these endogenous ligands, little is known about the key pharmacophore elements for ligand-RAGE interaction and the specific mode of binding. On these grounds, we aimed at designing new small molecules able to bind the VC1 extracellular domains of RAGE, in order to clarify the structural features that account for RAGE affinity and activation, and to identify new drug-like compounds. Following a process of structural simplification of known pyrazole-5-carboxamide RAGE ligands,1 we planned a set of novel derivatives characterized by a variously functionalized 3-cyclopropyl-4-phenoxy-1H-pyrazole scaffold (Figure 1). The design and synthesis of the new putative RAGE ligands will be presented and discussed, together with the results of their in vitro screening by means of a surface plasmon resonance (SPR)-based assay to estimate their binding ability to the RAGE extracellular domain. References 1. Bongarzone S., Savickas V., Luzi F., Gee A. D. J. Med. Chem. 2017, 60, 7213-7232. 2. Hudson B. I., Carter A. M., Harja E., Kalea A. Z., Arriero M., Yang H., Grant P. J., Schmidt A. M. FASEB J. 2008, 22, 1572-1580. 3. Xue J., Rai V., Singer D., Chabierski S., Xie J., Reverdatto S., Burz D. S., Schmidt A. M., Hoffmann R., Shekhtman A. Structure 2011, 19, 722\u2013732. 4. Koch M., Chitayat S., Dattilo B. M., Schiefner A., Diez J., Chazin W. J., Fritz, G. Structure 2010, 18, 1342-1352

Tailoring lipoplex composition to the lipid composition of plasma membrane: a Trojan horse for cell entry?

The first interaction between lipoplexes and cells is charge-mediated and not specific. Endocytosis is considered to be the main pathway for lipoplex entry. Upon interaction between lipoplexes and the plasma membrane, intermixing between lipoplex and membrane lipids is necessary for efficient endocytosis. Here we study the mechanism of the different endocytic pathways in lipid-mediated gene delivery. We show that DC-Chol-DOPE/DNA lipoplexes preferentially use a raftmediated endocytosis, while DOTAP-DOPC/DNA systems are mainly internalized by not specific fluid phase macropinocitosys. On the other hand, most efficient multicomponent lipoplexes, incorporating different lipid species in their lipid bilayer, can use multiple endocytic pathways to enter cells.Our data demonstrate that efficiency of endocytosis is regulated by shape coupling between lipoplex and membrane lipids. We suggest that such a shape-dependent coupling regulates efficient formation of endocytic vesicles thus determining the success of internalization. Our results suggest that tailoring the lipoplex lipid composition to the patchwork-like plasma membrane profile could be a successful machinery of coordinating the endocytic pathway activities and the subsequent intracellular processing