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Sample records for aldo morselli infn

  1. Enrico Morselli's Psychology and "Spiritism": psychiatry, psychology and psychical research in Italy in the decades around 1900.

    PubMed

    Brancaccio, Maria Teresa

    2014-12-01

    This paper traces Enrico Morselli's intellectual trajectory from the 1870s to the early 1900s. His interest in phenomena of physical mediumship is considered against the backdrop of the theoretical developments in Italian psychiatry and psychology. A leading positivist psychiatrist and a prolific academic, Morselli was actively involved in the making of Italian experimental psychology. Initially sceptical of psychical research and opposed to its association with the 'new psychology', Morselli subsequently conducted a study of the physical phenomena produced by the medium Eusapia Palladino. He concluded that her phenomena were genuine and represented them as the effects of an unknown bio-psychic force present in all human beings. By contextualizing Morselli's study of physical mediumship within contemporary theoretical and disciplinary discourse, this study elaborates shifts in the interpretations of 'supernormal' phenomena put forward by leading Italian psychiatrists and physiologists. It demonstrates that Morselli's interest in psychical research stems from his efforts to comprehend the determinants of complex psychological phenomena at a time when the dynamic theory of matter in physics, and the emergence of neo-vitalist theories influenced the theoretical debates in psychiatry, psychology and physiology.

  2. INFN Tier-1 Testbed Facility

    NASA Astrophysics Data System (ADS)

    Gregori, Daniele; Cavalli, Alessandro; dell'Agnello, Luca; Dal Pra, Stefano; Prosperini, Andrea; Ricci, Pierpaolo; Ronchieri, Elisabetta; Sapunenko, Vladimir

    2012-12-01

    INFN-CNAF, located in Bologna, is the Information Technology Center of National Institute of Nuclear Physics (INFN). In the framework of the Worldwide LHC Computing Grid, INFN-CNAF is one of the eleven worldwide Tier-1 centers to store and reprocessing Large Hadron Collider (LHC) data. The Italian Tier-1 provides the resources of storage (i.e., disk space for short term needs and tapes for long term needs) and computing power that are needed for data processing and analysis to the LHC scientific community. Furthermore, INFN Tier-1 houses computing resources for other particle physics experiments, like CDF at Fermilab, SuperB at Frascati, as well as for astro particle and spatial physics experiments. The computing center is a very complex infrastructure, the hardaware layer include the network, storage and farming area, while the software layer includes open source and proprietary software. Software updating and new hardware adding can unexpectedly deteriorate the production activity of the center: therefore a testbed facility has been set up in order to reproduce and certify the various layers of the Tier-1. In this article we describe the testbed and the checks performed.

  3. Aldo Leopold: An American Prophet

    ERIC Educational Resources Information Center

    Frese, Stephen J.

    2003-01-01

    In 1935, Aldo Leopold bought an abandoned farm in the sand counties along the Wisconsin River near Baraboo. Leopold sensed promise in the land, and with his wife and five children nursed the land back to health. They cleaned out the chicken coop and affectionately called their new family retreat "The Shack." Leopold kept detailed notes during the…

  4. INFN-CNAF Monitor and Control System

    NASA Astrophysics Data System (ADS)

    Antonelli, Stefano; De Girolamo, Donato; dell'Agnello, Luca; Gregori, Daniele; Guizzunti, Guido; Ricci, Pier Paolo; Rosso, Felice; Sapunenko, Vladimir; Veraldi, Riccardo; Veronesi, Paolo; Vistoli, Cristina; Vita Finzi, Giulia; Zani, Stefano

    2011-12-01

    CNAF is the national center of National Institute of Nuclear Physics (INFN) for R&D in the field of Information Technologies applied to High Energy Physics (HEP) experiments. It is involved in the management and development of the most important information and data handling services in behalf of the INFN. In 2005, the Italian Tier-1 for Large Hadron Collider (LHC) experiments has been inaugurated at INFN-CNAF. Due to the huge complexity of Tier-1 center, the use of control systems is fundamental for management and operation of the center. At INFN-CNAF, several solutions have been adopted, from commercial to open source products up to entirely home-made systems. Adopted open source solutions have been strongly adapted to specific needs; a wide set of customized sensors has been developed for various divisions like Network, Storage, Farming, Grid operation and National Services. Finally, a dashboard has been developed, to which described control systems send critical alarms (sent via sms to an operator as well). The dashboard can be exploited to get an historical view of the Tier-1 and national services' state and to allow a quick web control. In this article, the whole system, adopted customizations in monitoring and control as well as their integrations with the dashboard will be described.

  5. 75 FR 33573 - Information Collection; Aldo Leopold Wilderness Research Institute Wilderness Visitor Study

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-14

    ... Forest Service Information Collection; Aldo Leopold Wilderness Research Institute Wilderness Visitor... organizations on the new information collection: Aldo Leopold Wilderness Research Institute Wilderness Visitor...: Comments concerning this notice should be addressed to Alan Watson, Aldo Leopold Wilderness...

  6. Functional studies of aldo-keto reductases in Saccharomyces cerevisiae.

    PubMed

    Chang, Qing; Griest, Terry A; Harter, Theresa M; Petrash, J Mark

    2007-03-01

    We utilized the budding yeast Saccharomyces cerevisiae as a model to systematically explore physiological roles for yeast and mammalian aldo-keto reductases. Six open reading frames encoding putative aldo-keto reductases were identified when the yeast genome was queried against the sequence for human aldose reductase, the prototypical mammalian aldo-keto reductase. Recombinant proteins produced from five of these yeast open reading frames demonstrated NADPH-dependent reductase activity with a variety of aldehyde and ketone substrates. A triple aldo-keto reductase null mutant strain demonstrated a glucose-dependent heat shock phenotype which could be rescued by ectopic expression of human aldose reductase. Catalytically-inactive mutants of human or yeast aldo-keto reductases failed to effect a rescue of the heat shock phenotype, suggesting that the phenotype results from either an accumulation of one or more unmetabolized aldo-keto reductase substrates or a synthetic deficiency of aldo-keto reductase products generated in response to heat shock stress. These results suggest that multiple aldo-keto reductases fulfill functionally redundant roles in the stress response in yeast. PMID:17140678

  7. Functional studies of aldo-keto reductases in Saccharomyces cerevisiae*

    PubMed Central

    Chang, Qing; Griest, Terry A.; Harter, Theresa M.; Petrash, J. Mark

    2007-01-01

    SUMMARY We utilized the budding yeast Saccharomyces cerevisiae as a model to systematically explore physiological roles for yeast and mammalian aldo-keto reductases. Six open reading frames encoding putative aldo-keto reductases were identified when the yeast genome was queried against the sequence for human aldose reductase, the prototypical mammalian aldo-keto reductase. Recombinant proteins produced from five of these yeast open reading frames demonstrated NADPH-dependent reductase activity with a variety of aldehyde and ketone substrates. A triple aldo-keto reductase null mutant strain demonstrated a glucose-dependent heat shock phenotype which could be rescued by ectopic expression of human aldose reductase. Catalytically-inactive mutants of human or yeast aldo-keto reductases failed to effect a rescue of the heat shock phenotype, suggesting that the phenotype results from either an accumulation of one or more unmetabolized aldo-keto reductase substrates or a synthetic deficiency of aldo-keto reductase products generated in response to heat shock stress. These results suggest that multiple aldo-keto reductases fulfill functionally redundant roles in the stress response in yeast. PMID:17140678

  8. The aldo-keto reductase superfamily homepage.

    PubMed

    Hyndman, David; Bauman, David R; Heredia, Vladi V; Penning, Trevor M

    2003-02-01

    The aldo-keto reductases (AKRs) are one of the three enzyme superfamilies that perform oxidoreduction on a wide variety of natural and foreign substrates. A systematic nomenclature for the AKR superfamily was adopted in 1996 and was updated in September 2000 (visit www.med.upenn.edu/akr). Investigators have been diligent in submitting sequences of functional proteins to the Web site. With the new additions, the superfamily contains 114 proteins expressed in prokaryotes and eukaryotes that are distributed over 14 families (AKR1-AKR14). The AKR1 family contains the aldose reductases, the aldehyde reductases, the hydroxysteroid dehydrogenases and steroid 5beta-reductases, and is the largest. Other families of interest include AKR6, which includes potassium channel beta-subunits, and AKR7 the aflatoxin aldehyde reductases. Two new families include AKR13 (yeast aldose reductase) and AKR14 (Escherichia coli aldehyde reductase). Crystal structures of many AKRs and their complexes with ligands are available in the PDB and accessible through the Web site. Each structure has the characteristic (alpha/beta)(8)-barrel motif of the superfamily, a conserved cofactor binding site and a catalytic tetrad, and variable loop structures that define substrate specificity. Although the majority of AKRs are monomeric proteins of about 320 amino acids in length, the AKR2, AKR6 and AKR7 family may form multimers. To expand the nomenclature to accommodate multimers, we recommend that the composition and stoichiometry be listed. For example, AKR7A1:AKR7A4 (1:3) would designate a tetramer of the composition indicated. The current nomenclature is recognized by the Human Genome Project (HUGO) and the Web site provides a link to genomic information including chromosomal localization, gene boundaries, human ESTs and SNPs and much more.

  9. The aldo-keto reductases (AKRs): Overview.

    PubMed

    Penning, Trevor M

    2015-06-01

    The aldo-keto reductase (AKR) protein superfamily contains >190 members that fall into 16 families and are found in all phyla. These enzymes reduce carbonyl substrates such as: sugar aldehydes; keto-steroids, keto-prostaglandins, retinals, quinones, and lipid peroxidation by-products. Exceptions include the reduction of steroid double bonds catalyzed by AKR1D enzymes (5β-reductases); and the oxidation of proximate carcinogen trans-dihydrodiol polycyclic aromatic hydrocarbons; while the β-subunits of potassium gated ion channels (AKR6 family) control Kv channel opening. AKRs are usually 37kDa monomers, have an (α/β)8-barrel motif, display large loops at the back of the barrel which govern substrate specificity, and have a conserved cofactor binding domain. AKRs catalyze an ordered bi bi kinetic mechanism in which NAD(P)H cofactor binds first and leaves last. In enzymes that favor NADPH, the rate of release of NADP(+) is governed by a slow isomerization step which places an upper limit on kcat. AKRs retain a conserved catalytic tetrad consisting of Tyr55, Asp50, Lys84, and His117 (AKR1C9 numbering). There is conservation of the catalytic mechanism with short-chain dehydrogenases/reductases (SDRs) even though they show different protein folds. There are 15 human AKRs of these AKR1B1, AKR1C1-1C3, AKR1D1, and AKR1B10 have been implicated in diabetic complications, steroid hormone dependent malignancies, bile acid deficiency and defects in retinoic acid signaling, respectively. Inhibitor programs exist world-wide to target each of these enzymes to treat the aforementioned disorders. Inherited mutations in AKR1C and AKR1D1 enzymes are implicated in defects in the development of male genitalia and bile acid deficiency, respectively, and occur in evolutionarily conserved amino acids. The human AKRs have a large number of nsSNPs and splice variants, but in many instances functional genomics is lacking. AKRs and their variants are now poised to be interrogated using

  10. Comparative anatomy of the aldo-keto reductase superfamily.

    PubMed Central

    Jez, J M; Bennett, M J; Schlegel, B P; Lewis, M; Penning, T M

    1997-01-01

    The aldo-keto reductases metabolize a wide range of substrates and are potential drug targets. This protein superfamily includes aldose reductases, aldehyde reductases, hydroxysteroid dehydrogenases and dihydrodiol dehydrogenases. By combining multiple sequence alignments with known three-dimensional structures and the results of site-directed mutagenesis studies, we have developed a structure/function analysis of this superfamily. Our studies suggest that the (alpha/beta)8-barrel fold provides a common scaffold for an NAD(P)(H)-dependent catalytic activity, with substrate specificity determined by variation of loops on the C-terminal side of the barrel. All the aldo-keto reductases are dependent on nicotinamide cofactors for catalysis and retain a similar cofactor binding site, even among proteins with less than 30% amino acid sequence identity. Likewise, the aldo-keto reductase active site is highly conserved. However, our alignments indicate that variation ofa single residue in the active site may alter the reaction mechanism from carbonyl oxidoreduction to carbon-carbon double-bond reduction, as in the 3-oxo-5beta-steroid 4-dehydrogenases (Delta4-3-ketosteroid 5beta-reductases) of the superfamily. Comparison of the proposed substrate binding pocket suggests residues 54 and 118, near the active site, as possible discriminators between sugar and steroid substrates. In addition, sequence alignment and subsequent homology modelling of mouse liver 17beta-hydroxysteroid dehydrogenase and rat ovary 20alpha-hydroxysteroid dehydrogenase indicate that three loops on the C-terminal side of the barrel play potential roles in determining the positional and stereo-specificity of the hydroxysteroid dehydrogenases. Finally, we propose that the aldo-keto reductase superfamily may represent an example of divergent evolution from an ancestral multifunctional oxidoreductase and an example of convergent evolution to the same active-site constellation as the short

  11. Origin and Status of the Gran Sasso INFN Laboratory

    NASA Astrophysics Data System (ADS)

    Votano, Lucia

    2014-06-01

    The Gran Sasso National Laboratory of INFN (LNGS) is the largest underground laboratory for astroparticle physics in the world. Located in Italy between the cities of L'Aquila and Teramo, 120 Km far from Rome, is a research infrastructure mainly dedicated to astroparticle and neutrino physics. It offers the most advanced underground facility in terms of dimensions, complexity and completeness of its infrastructures. LNGS is one of the four national laboratories run by the INFN (Istituto Nazionale di Fisica Nucleare). The scientific program at LNGS is mainly focused on astroparticle, particle and nuclear physics. The laboratory presently hosts many experiments as well as R&D activities, including world-leading research in the fields of solar neutrinos, accelerator neutrinos (CNGS neutrino beam from CERN to Gran Sasso), dark matter, neutrinoless double beta decay and nuclear cross section of astrophysical interest. Associate sciences like earth physics, biology and fundamental physics complement the activities. The laboratory is operated as an international science facility and hosts experiments whose scientific merit is assessed by an international advisory Scientific Committee. A review of the main experiments carried out at LNGS will be given, together with the most recent and relevant scientific results achieved.

  12. Origin and status of the Gran Sasso INFN Laboratory

    NASA Astrophysics Data System (ADS)

    Votano, Lucia

    2014-11-01

    The Gran Sasso National Laboratory of INFN (LNGS) is the largest underground laboratory for astroparticle physics in the world. Located in Italy between the cities of L'Aquila and Teramo, 120 km far from Rome, is a research infrastructure mainly dedicated to astroparticle and neutrino physics. It offers the most advanced underground facility in terms of dimensions, complexity and completeness of its infrastructures. LNGS is one of the four national laboratories run by the Istituto Nazionale di Fisica Nucleare (INFN). The scientific program at LNGS is mainly focused on astroparticle, particle and nuclear physics. The laboratory presently hosts many experiments as well as R&D activities, including world-leading research in the fields of solar neutrinos, accelerator neutrinos (CNGS neutrino beam from CERN to Gran Sasso), dark matter (DM), neutrinoless double beta decay (2β0ν) and nuclear cross-section of astrophysical interest. Associate sciences like earth physics, biology and fundamental physics complement the activities. The laboratory is operated as an international science facility and hosts experiments whose scientific merit is assessed by an international advisory Scientific Committee. A review of the main experiments carried out at LNGS will be given, together with the most recent and relevant scientific results achieved.

  13. Diamond dosimetry: Outcomes of the CANDIDO and CONRAD INFN projects

    NASA Astrophysics Data System (ADS)

    Bucciolini, M.; Borchi, E.; Bruzzi, M.; Casati, M.; Cirrone, P.; Cuttone, G.; De Angelis, C.; Lovik, I.; Onori, S.; Raffaele, L.; Sciortino, S.

    2005-10-01

    This paper reviews the main results of the study, carried out in the framework of the Italian National Institute of Nuclear Physics (INFN, Istituto Nazionale di Fisica Nucleare) projects, namely CANDIDO and CONRAD, on natural and synthetic diamond-based dosimeters for clinical radiotherapy. Characteristics of diamond such as radiation hardness, high sensitivity, tissue equivalence, etc., make this material interesting for dosimetry applications. For some years, natural diamonds have been commercially available for on-line radiotherapy dosimetry. Nevertheless, recent developments in the "Chemical Vapour Deposition" (CVD) technique have addressed the attention on synthetic samples that potentially could be grown at low cost and with features suitable for dosimetric use. Several samples, differently grown and with different electrical contacts, have been compared by measuring their current response during irradiation with high-energy photon, electron and proton beams. Properties of dosimetric interest such as linearity, pre-irradiation dose, dose rate dependence, stability and rise time have been investigated. The results obtained so far within the INFN collaboration demonstrate the suitability of natural diamond detectors for many radiotherapy applications and the great potential of CVD diamond-based devices even though, at present, the commercial natural diamond dosimeters have a better behaviour with respect to the synthetic samples. Further efforts have to be made mainly to improve the dynamic of response and performance stability.

  14. DAFNE-Light INFN-LNF Synchrotron Radiation Facility

    SciTech Connect

    Balerna, A.; Cestelli-Guidi, M.; Cimino, R.; Commisso, M.; Grilli, A.; Pietropaoli, M.; Raco, A.; Sciarra, V.; Tullio, V.; Viviani, G.; De Sio, A.; Gambicorti, L.; Hampai, D.; Pace, E.

    2010-06-23

    DAFNE-Light is the Synchrotron Radiation Facility at the INFN-Frascati National Laboratory (Rome, Italy). Three beamlines are operational, using in parasitic and dedicated mode the intense photon emission of DAFNE, a 0.51 GeV storage ring with a routinely circulating electron current higher than 1 Ampere. Two of these beamlines--the soft x-ray (DXR1) and UV (DXR2)--use one of the DAFNE wiggler magnets as synchrotron radiation source, while the third beamline SINBAD (Synchrotron Infrared Beamline At DAFNE) collects the radiation from a bending magnet. New XUV bending magnet beamlines are nowadays under construction and the low energy one (35-200 eV) will be ready for commissioning by the end of 2009. A presentation of the facility will be given together with some recent scientific results achieved at SINBAD and DXR1 beamlines.

  15. Docker experience at INFN-Pisa Grid Data Center

    NASA Astrophysics Data System (ADS)

    Mazzoni, E.; Arezzini, S.; Boccali, T.; Ciampa, A.; Coscetti, S.; Bonacorsi, D.

    2015-12-01

    Clouds and virtualization offer typical answers to the needs of large-scale computing centers to satisfy diverse sets of user communities in terms of architecture, OS, etc. On the other hand, solutions like Docker seems to emerge as a way to rely on Linux kernel capabilities to package only the applications and the development environment needed by the users, thus solving several resource management issues related to cloud-like solutions. In this paper, we present an exploratory (though well advanced) test done at a major Italian Tier2, at INFN-Pisa, where a considerable fraction of the resources and services has been moved to Docker. The results obtained are definitely encouraging, and Pisa is transitioning all of its Worker Nodes and services to Docker containers. Work is currently being expanded into the preparation of suitable images for a completely virtualized Tier2, with no dependency on local configurations.

  16. The INFN-FBK "Phase-2" R&D program

    NASA Astrophysics Data System (ADS)

    Dalla Betta, G.-F.; Boscardin, M.; Bomben, M.; Brianzi, M.; Calderini, G.; Darbo, G.; Dell'Orso, R.; Gaudiello, A.; Giacomini, G.; Mendicino, R.; Meschini, M.; Messineo, A.; Ronchin, S.; Sultan, D. M. S.; Zorzi, N.

    2016-07-01

    We report on the 3-year INFN ATLAS-CMS joint research activity in collaboration with FBK, started in 2014, and aimed at the development of new thin pixel detectors for the High Luminosity LHC Phase-2 upgrades. The program is concerned with both 3D and planar active-edge pixel sensors to be made on 6" p-type wafers. The technology and the design will be optimized and qualified for extreme radiation hardness (2×1016 neq cm-2). Pixel layouts compatible with present (for testing) and future (RD53 65 nm) front-end chips of ATLAS and CMS are considered. The paper covers the main aspects of the research program, from the sensor design and fabrication technology, to the results of initial tests performed on the first prototypes.

  17. CARE activities on superconducting RF cavities at INFN Milano

    NASA Astrophysics Data System (ADS)

    Bosotti, A.; Pierini, P.; Michelato, P.; Pagani, C.; Paparella, R.; Panzeri, N.; Monaco, L.; Paulon, R.; Novati, M.

    2005-09-01

    The SC RF group at INFN Milano-LASA is involved both in the TESLA/TTF collaboration and in the research and design activity on superconducting cavities for proton accelerators. Among these activities, some are supported by the European community within the CARE project. In the framework of the JRASRF collaboration we are developing a coaxial blade tuner for ILC (International Linear Collider) cavities, integrated with piezoelectric actuators for the compensation of the Lorenz force detuning and microphonics perturbation. Another activity, regarding the improved component design on SC technology, based on the information retrieving about the status of art on ancillaries and experience of various laboratories involved in SCRF, has started in our laboratory. Finally, in the framework of the HIPPI collaboration, we are testing two low beta superconducting cavities, built for the Italian TRASCO project, to verify the possibility to use them for pulsed operation. All these activities will be described here, together with the main results and the future perspectives.

  18. Application of the Ta liner technique to produce Ca beams at INFN-Legnaro National Laboratories (INFN-LNL)

    SciTech Connect

    Galatà, A. Sattin, M.; Manzolaro, M.; Martini, D.; Facco, A.; Tinschert, K.; Spaedtke, P.; Lang, R.; Kulevoy, T.

    2014-02-15

    The ECR ion sources are able to produce a wide variety of highly charged metallic ion beams thanks to the development of different techniques (ovens, sputtering, direct insertion, metal ions from volatile compounds (MIVOC)). In the case of the ovens, the sticking of the hot vapors on the surface of the plasma chamber leads to high material consumption rates. For elements like Ca, a tantalum liner inserted inside the chamber can be used to limit this phenomenon. The modeling of temperature distribution inside the chamber with and without the liner was carried out with COMSOL-multiphysics code. Results of simulation and the comparison with experiments performed at INFN-Legnaro National Laboratories with Ca beams are discussed.

  19. Age-Specific Peculiarities of Modulation of Blood Aldo-Keto Reductase Isoenzyme Spectrum.

    PubMed

    Davydov, V V

    2015-12-01

    The aldo-keto reductase spectrum of the blood was studied at different stages of ontogeny to elucidate the role of reduction pathway in utilization of the carbonyl products of free radical oxidation in modulation of organism sensitivity to the damaging effect of stress during ontogeny. The studies revealed the age-specific changes in aldo-keto reductase spectrum in the blood. An analogy of the aldo-keto reductase spectrum structure in animals of early maturity and in old rats was found. The appearance of age specificity of the aldo-keto reductase spectrum in the blood creates metabolic prerequisites for changes in the efficiency of utilization of carbonyl products of free radical oxidation via their reductive transformation.

  20. To Learn Is To Grow, I: Aldo Leopold, Predator Eradication, and Games Refuges.

    ERIC Educational Resources Information Center

    Dolph, Gary E.

    1998-01-01

    Follows the evolution in the thinking of Aldo Leopold, a game manager who was initially an advocate of predator eradication but who came to see predators as playing an important role in normally functioning ecosystems. (DDR)

  1. The SPES Radioactive Ion Beam facility of INFN

    NASA Astrophysics Data System (ADS)

    de Angelis, G.; Spes Collaboration; Prete, G.; Andrighetto, A.; Manzolaro, M.; Corradetti, S.; Scarpa, D.; Rossignoli, M.; Monetti, A.; Lollo, M.; Calderolla, M.; Vasquez, J.; Zafiropoulos, D.; Sarchiapone, L.; Benini, D.; Favaron, P.; Rigato, M.; Pegoraro, R.; Maniero, D.; Calabretta, L.; Comunian, M.; Maggiore, M.; Lombardi, A.; Piazza, L.; Porcellato, A. M.; Roncolato, C.; Bisoffi, G.; Pisent, A.; Galatà, A.; Giacchini, M.; Bassato, G.; Canella, S.; Gramegna, F.; Valiente, J.; Bermudez, J.; Mastinu, P. F.; Esposito, J.; Wyss, J.; Russo, A.; Zanella, S.

    2015-02-01

    A new Radioactive Ion Beam (RIB) facility (SPES) is presently under construction at the Legnaro National Laboratories of INFN. The SPES facility is based on the ISOL method using an UCx Direct Target able to sustain a power of 10 kW. The primary proton beam is provided by a high current Cyclotron accelerator with energy of 40 MeV and a beam current of 0.2-0.5 mA. Neutron-rich radioactive ions are produced by proton induced fission at an expected fission rate of the order of 1013 fissions per second. After ionization and selection the exotic isotopes are re-accelerated by the ALPI superconducting LINAC at energies of 10A MeV for masses in the region A=130 amu. The expected secondary beam rates are of the order of 107 - 109 pps. Aim of the SPES facility is to deliver high intensity radioactive ion beams of neutron rich nuclei for nuclear physics research as well as to be an interdisciplinary research center for radio-isotopes production for medicine and for neutron beams.

  2. The SPES project at the INFN- Laboratori Nazionali di Legnaro

    NASA Astrophysics Data System (ADS)

    Pretea, G.; Andrighetto, A.; Manzolaro, M.; Corradetti, S.; Scarpa, D.; Rossignoli, M.; Monetti, A.; Lollo, M.; Calderolla, M.; Vasquez, J.; Zafiropoulos, D.; Sarchiapone, L.; Benini, D.; Favaron, P.; Rigato, M.; Pegoraro, R.; Maniero, D.; Calabretta, L.; Comunian, M.; Maggiore, M.; Lombardi, A.; Piazza, L.; Porcellato, A. M.; Roncolato, C.; Bisoffi, G.; Pisent, A.; Galatà, A.; Giacchini, M.; Bassato, G.; Canella, S.; Gramegna, F.; Valiente, J.; Bermudez, J.; Mastinu, P. F.; Esposito, J.; Wyss, J.; Zanella, S.

    2014-03-01

    The SPES Radioactive Ion Beam (RIB) facility at INFN-LNL is in the construction phase. It is based on the ISOL method with an UCx Direct Target able to sustain a power of 10 kW. The primary proton beam is delivered by a high current Cyclotron accelerator, with energy 35-70 MeV and a beam current of 0.2-0.5 mA. Neutron-rich radioactive ions will be produced by proton induced Uranium fission in the UCx target at an expected fission rate in the order of 1013 fissions per second. The exotic isotopes will be re-accelerated by the ALPI superconducting LINAC at energies of 10A MeV and higher, for masses in the region A=130 amu at expected rate on the secondary target of 107 - 109 pps. The SPES project has the aim to provide high intensity and highquality beams of neutron-rich nuclei as well as to develop an interdisciplinary research center based on the cyclotron proton beam.

  3. The SPES Radioactive-Ion Beam Facility of INFN

    NASA Astrophysics Data System (ADS)

    de Angelis, G.; Prete, G.; Andrighetto, A.; Manzolaro, M.; Corradetti, S.; Scarpa, D.; Rossignoli, M.; Monetti, A.; Lollo, M.; Calderolla, M.; Vasquez, J.; Zafiropoulos, D.; Sarchiapone, L.; Benini, D.; Favaron, P.; Rigato, M.; Pegoraro, R.; Maniero, D.; Comunian, M.; Maggiore, M.; Lombardi, A.; Piazza, L.; Porcellato, A. M.; Roncolato, C.; Bisoffi, G.; Pisent, A.; Galatà, A.; Giacchini, M.; Bassato, G.; Canella, S.; Gramegna, F.; Valiente, J.; Bermudez, J.; Mastinu, P. F.; Esposito, J.; Wyss, J.; Russo, A.; Zanella, S.; Calabretta, L.

    2015-11-01

    A new radioactive-ion beam (RIB) facility (SPES) is presently under construction at the Legnaro National Laboratories of INFN. The SPES facility is based on the ISOL method using a UCx direct target able to sustain a power of 10 kW. The primary proton beam will be provided by a high-current cyclotron accelerator with energy of 35-70 MeV and a beam current of 0.2-0.5 mA. Neutron-rich radioactive ions will be produced by proton-induced fission on a uranium target at an expected fission rate of the order of 1013 fissions per second. After ionization and selection the exotic isotopes will be re-accelerated by the ALPI superconducting LINAC at energies of 10A MeV for masses in the region A=130 amu. The expected secondary beam rates are of the order of 107-109 pps. The aim of the SPES facility is to deliver high-intensity radioactive-ion beams of neutron-rich nuclei for nuclear physics research, as well as to be an interdisciplinary research center for radioisotope production for medicine and for neutron beams.

  4. The SPES radioactive ion beam project of INFN

    NASA Astrophysics Data System (ADS)

    de Angelis, Giacomo; Spes Collaboration; Prete, G.; Andrighetto, A.; Manzolaro, M.; Corradetti, S.; Scarpa, D.; Rossignoli, M.; Monetti, A.; Lollo, M.; Calderolla, M.; Vasquez, J.; Zafiropoulos, D.; Sarchiapone, L.; Benini, D.; Favaron, P.; Rigato, M.; Pegoraro, R.; Maniero, D.; Calabretta, L.; Comunian, M.; Maggiore, M.; Lombardi, A.; Piazza, L.; Porcellato, A. M.; Roncolato, C.; Bisoffi, G.; Pisent, A.; Galatà, A.; Giacchini, M.; Bassato, G.; Canella, S.; Gramegna, F.; Valiente, J.; Bermudez, J.; Mastinu, P. F.; Esposito, J.; Wyss, J.; Russo, A.; Zanella, S.

    2014-07-01

    The SPES Radioactive Ion Beam facility at INFN-LNL is presently in the construction phase. The facility is based on the Isol (Isotope separation on-line) method with an UCx Direct Target able to sustain a power of 10 kW. The primary proton beam is provided by a high current Cyclotron accelerator with energy of 35-70 MeV and a beam current of 0.20.5 mA. Neutron-rich radioactive ions are produced by proton induced Uranium fission at an expected fission rate of the order of 1013 fissions per second. After ionization and selection the exotic isotopes are re-accelerated by the ALPI superconducting Linac at energies of 10A MeV for masses in the region A = 130 amu. The expected secondary beam rates are of the order of 107 - 109 pps. Aim of the SPES project is to provide a facility for high intensity radioactive ion beams for nuclear physics research as well as to develop an interdisciplinary research center based on the cyclotron proton beam.

  5. Recent progress in plasma modelling at INFN-LNS

    NASA Astrophysics Data System (ADS)

    Neri, L.; Castro, G.; Torrisi, G.; Galatà, A.; Mascali, D.; Celona, L.; Gammino, S.

    2016-02-01

    At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via "cold" approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an "as-a-whole" picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase.

  6. Francium trapping at the INFN-LNL facility

    NASA Astrophysics Data System (ADS)

    Mariotti, E.; Khanbekyan, A.; Marinelli, C.; Marmugi, L.; Moi, L.; Corradi, L.; Dainelli, A.; Calabrese, R.; Mazzocca, G.; Tomassetti, L.

    2014-05-01

    A brief review of the Francium trapping experiments at the INFN-LNL facility is presented in the wide context of Atomic Parity-Nonconservation (APNC), which, as long as acquiring more precise and new spectroscopic data on the Francium isotopes, is the ultimate goal of the experiment. Due to its instability, Francium atoms must be produced continuously by a nuclear fusion-evaporation reaction into a heated Gold target hit by a beam of accelerated oxygen ions. Francium is then extracted in the ionic form and guided by an electrostatic line to the actual science chamber, where the ions are neutralized. Atoms are then cooled down and trapped in a Magneto-Optical Trap (MOT) to ensure both the availability of a sufficiently populated and stable atomic sample and to eliminate the Doppler broadening which would affect the precision of the measurements. A review of the recent improvements to the experimental apparatus and to the detection techniques that led to a sensitivity better than five atoms is presented. The final part of this paper deals with a summary of the recent results obtained by our collaboration and a short outlook for the immediate future.

  7. Recent progress in plasma modelling at INFN-LNS.

    PubMed

    Neri, L; Castro, G; Torrisi, G; Galatà, A; Mascali, D; Celona, L; Gammino, S

    2016-02-01

    At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via "cold" approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an "as-a-whole" picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase.

  8. Recent progress in plasma modelling at INFN-LNS.

    PubMed

    Neri, L; Castro, G; Torrisi, G; Galatà, A; Mascali, D; Celona, L; Gammino, S

    2016-02-01

    At Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali del Sud (INFN-LNS), the development of intense ion and proton sources has been supported by a great deal of work on the modelling of microwave generated plasmas for many years. First, a stationary version of the particle-in-cell code was developed for plasma modelling starting from an iterative strategy adopted for the space charge dominated beam transport simulations. Electromagnetic properties of the plasma and full-waves simulations are now affordable for non-homogenous and non-isotropic magnetized plasma via "cold" approximation. The effects of Coulomb collisions on plasma particles dynamics was implemented with the Langevin formalism, instead of simply applying the Spitzer 90° collisions through a Monte Carlo technique. A wide database of different cross sections related to reactions occurring in a hydrogen plasma was implemented. The next step consists of merging such a variety of approaches for retrieving an "as-a-whole" picture of plasma dynamics in ion sources. The preliminary results will be summarized in the paper for a microwave discharge ion source designed for intense and high quality proton beams production, proton source for European Spallation Source project. Even if the realization of a predictive software including the complete processes involved in plasma formation is still rather far, a better comprehension of the source behavior is possible and so the simulations may support the optimization phase. PMID:26931913

  9. Life as a sober citizen: Aldo Leopold's Wildlife Ecology 118

    NASA Astrophysics Data System (ADS)

    Theiss, Nancy Stearns

    This historic case study addressed the issue of the lack of citizen action toward environmentally responsible behavior. Although there have been studies regarding components of environmental responsible behavior [ERB], there has been little focus on historic models of exemplary figures of ERB. This study examined one of the first conservation courses in the United States, Wildlife Ecology 118, taught by Aldo Leopold (1887--1948) for 13 years at the University of Wisconsin. Today, Aldo Leopold is recognized as an exemplary conservationist whose land ethic is cited as providing the ecological approach needed for understanding the complex issues of modern society. The researcher conjectured that examination of one of the first environmental education courses could support and strengthen environmental education practices by providing a heuristic perspective. The researcher used two different strategies for analysis of the case. For Research Question One---"What were Leopold's teaching strategies in Wildlife Ecology 118?"---the researcher used methods of comparative historical analysis. The researcher examined the learning outcomes that Leopold used in Wildlife Ecology 118 and compared them against a rubric of the Four Strands for Environmental Education (North American Association for Environmental Education [NAAEE], 1999). The Four Strands for Environmental Education are the current teaching strategies used by educators. The results indicated that Wildlife Ecology 118 scored high in Knowledge of Processes and Systems and Environmental Problem Solving strands. Leopold relied on historic case examples and animal biographies to build stories that engaged students. Field trips gave students practical experience for environmental knowledge with special emphasis on phenology. For Research Question Two---"What was the context of the lessons in Wildlife Ecology 118?"---the researcher used environmental history methods for analysis. Context provided the knowledge and

  10. Risk management and the wisdom of Aldo Leopold.

    PubMed

    Warren, Julianne Lutz; Kieffer, Susan

    2010-02-01

    Human demands on nature have increased due to our burgeoning population. The applications of scientific knowledge to the development of increasingly powerful technologies and consumptive lifestyles by more and more people have created a modern category of human-caused disaster-stealth disasters. Stealth disasters-such as agriculturally-induced soil erosion and release of unprecedented amounts of greenhouse gases into Earth's atmosphere-tend to have protracted, unobvious onsets; do not necessarily have dramatic manifestations; and often do not attract public attention until they reach a stage approaching catastrophic consequences. At this late stage it is difficult or impossible to undo damage. Scientists tend to be among the first to understand the physical causes and notice the developments of stealth disasters and their risks and yet scientific knowledge is not enough to prevent or mitigate them. As we search for ways to deal with stealth disasters, the concept of "land health" assembled by the prominent conservationist and author, Aldo Leopold (1887-1948), can, in normative terms, provide an ecologically grounded example of nature in good condition toward which society can aim. Evidence of the reverse-symptoms of land illness-can provide a checklist for risk analysis and management that helps guide people away from harm-causing attitudes and activities and toward beneficial outcomes. Leopold's criteria of land health motivated by a land ethic that incorporates the whole of nature may be applied at geographic scales ranging from local to global as a framework for contemporary risk management.

  11. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.

    PubMed

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions.

  12. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology

    PubMed Central

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A. Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

  13. Aldo-Keto Reductases 1B in Adrenal Cortex Physiology.

    PubMed

    Pastel, Emilie; Pointud, Jean-Christophe; Martinez, Antoine; Lefrançois-Martinez, A Marie

    2016-01-01

    Aldose reductase (AKR1B) proteins are monomeric enzymes, belonging to the aldo-keto reductase (AKR) superfamily. They perform oxidoreduction of carbonyl groups from a wide variety of substrates, such as aliphatic and aromatic aldehydes or ketones. Due to the involvement of human aldose reductases in pathologies, such as diabetic complications and cancer, AKR1B subgroup enzymatic properties have been extensively characterized. However, the issue of AKR1B function in non-pathologic conditions remains poorly resolved. Adrenal activities generated large amount of harmful aldehydes from lipid peroxidation and steroidogenesis, including 4-hydroxynonenal (4-HNE) and isocaproaldehyde (4-methylpentanal), which can both be reduced by AKR1B proteins. More recently, some AKR1B isoforms have been shown to be endowed with prostaglandin F synthase (PGFS) activity, suggesting that, in addition to possible scavenger function, they could instigate paracrine signals. Interestingly, the adrenal gland is one of the major sites for human and murine AKR1B expression, suggesting that their detoxifying/signaling activity could be specifically required for the correct handling of adrenal function. Moreover, chronic effects of ACTH result in a coordinated regulation of genes encoding the steroidogenic enzymes and some AKR1B isoforms. This review presents the molecular mechanisms accounting for the adrenal-specific expression of some AKR1B genes. Using data from recent mouse genetic models, we will try to connect their enzymatic properties and regulation with adrenal functions. PMID:27499746

  14. Functional genomic studies of aldo-keto reductases.

    PubMed

    Petrash, J M; Murthy, B S; Young, M; Morris, K; Rikimaru, L; Griest, T A; Harter, T

    2001-01-30

    Aldose reductase (AR) is considered a potential mediator of diabetic complications and is a drug target for inhibitors of diabetic retinopathy and neuropathy in clinical trials. However, the physiological role of this enzyme still has not been established. Since effective inhibition of diabetic complications will require early intervention, it is important to delineate whether AR fulfills a physiological role that cannot be compensated by an alternate aldo-keto reductase. Functional genomics provides a variety of powerful new tools to probe the physiological roles of individual genes, especially those comprising gene families. Several eucaryotic genomes have been sequenced and annotated, including yeast, nematode and fly. To probe the function of AR, we have chosen to utilize the budding yeast Saccharomyces cerevisiae as a potential model system. Unlike Caenorhabditis elegans and D. melanogaster, yeast provides a more desirable system for our studies because its genome is manipulated more readily and is able to sustain multiple gene deletions in the presence of either drug or auxotrophic selectable markers. Using BLAST searches against the human AR gene sequence, we identified six genes in the complete S. cerevisiae genome with strong homology to AR. In all cases, amino acids thought to play important catalytic roles in human AR are conserved in the yeast AR-like genes. All six yeast AR-like open reading frames (ORFs) have been cloned into plasmid expression vectors. Substrate and AR inhibitor specificities have been surveyed on four of the enzyme forms to identify, which are the most functionally similar to human AR. Our data reveal that two of the enzymes (YDR368Wp and YHR104Wp) are notable for their similarity to human AR in terms of activity with aldoses and substituted aromatic aldehydes. Ongoing studies are aimed at characterizing the phenotypes of yeast strains containing single and multiple knockouts of the AR-like genes. PMID:11306085

  15. Framing a Philosophy of Environmental Action: Aldo Leopold, John Muir, and the Importance of Community

    ERIC Educational Resources Information Center

    Goralnik, Lissy; Nelson, Michael P.

    2011-01-01

    A philosophy of action consists of a theory about how and why we do things and what motivates us to act. By juxtaposing the theory of environmental action implied by the works and life of John Muir with the philosophy of action suggested by Aldo Leopold's Land Ethic, we will illuminate the importance of a philosophy of action in determining one's…

  16. INFN-Pisa scientific computation environment (GRID, HPC and Interactive Analysis)

    NASA Astrophysics Data System (ADS)

    Arezzini, S.; Carboni, A.; Caruso, G.; Ciampa, A.; Coscetti, S.; Mazzoni, E.; Piras, S.

    2014-06-01

    The INFN-Pisa Tier2 infrastructure is described, optimized not only for GRID CPU and Storage access, but also for a more interactive use of the resources in order to provide good solutions for the final data analysis step. The Data Center, equipped with about 6700 production cores, permits the use of modern analysis techniques realized via advanced statistical tools (like RooFit and RooStat) implemented in multicore systems. In particular a POSIX file storage access integrated with standard SRM access is provided. Therefore the unified storage infrastructure is described, based on GPFS and Xrootd, used both for SRM data repository and interactive POSIX access. Such a common infrastructure allows a transparent access to the Tier2 data to the users for their interactive analysis. The organization of a specialized many cores CPU facility devoted to interactive analysis is also described along with the login mechanism integrated with the INFN-AAI (National INFN Infrastructure) to extend the site access and use to a geographical distributed community. Such infrastructure is used also for a national computing facility in use to the INFN theoretical community, it enables a synergic use of computing and storage resources. Our Center initially developed for the HEP community is now growing and includes also HPC resources fully integrated. In recent years has been installed and managed a cluster facility (1000 cores, parallel use via InfiniBand connection) and we are now updating this facility that will provide resources for all the intermediate level HPC computing needs of the INFN theoretical national community.

  17. The Long Term Data Preservation (LTDP) project at INFN CNAF: CDF use case

    NASA Astrophysics Data System (ADS)

    Amerio, S.; Chiarelli, L.; Dell'Agnello, L.; Gregori, D.; Pezzi, M.; Ricci, P.; Rosso, F.; Zani, S.

    2015-05-01

    In the last years the problem of preservation of scientific data has become one of the most important topics inside international scientific communities. In particular the long term preservation of experimental data, raw and all related derived formats including calibration information, is one of the emerging requirements within the High Energy Physics (HEP) community for experiments that have already concluded the data taking phase. The DPHEP group (Data Preservation in HEP) coordinates the local teams within the whole collaboration and the different Tiers (computing centers). The INFN-CNAF Tier-1 is one of the reference sites for data storage and computing in the LHC community but it also offers resources to many other HEP and non-HEP collaborations. In particular the CDF experiment has used the INFN-CNAF Tier-1 resources for many years and after the end of data taking in 2011, it is now facing the challenge to both preserve the large amount of data produced during several years and to retain the ability to access and reuse the whole amount of it in the future. According to this task the CDF Italian collaboration, together with the INFN-CNAF computing center, has developed and is now implementing a long term future data preservation project in collaboration with Fermilab (FNAL) computing sector. The project comprises the copy of all CDF raw data and user level ntuples (about 4 PB) at the INFN-CNAF site and the setup of a framework which will allow to access and analyze the data in the long term future. A portion of the 4 PB of data (raw data and analysis-level ntuples) are currently being copied from FNAL to the INFN-CNAF tape library backend and a system to allow data access is being setup. In addition to this data access system, a data analysis framework is being developed in order to run the complete CDF analysis chain in the long term future, from raw data reprocessing to analysis-level ntuples production and analysis. In this contribution we first illustrate

  18. Production of keto-disaccharides from aldo-disaccharides in subcritical aqueous ethanol.

    PubMed

    Gao, Da-Ming; Kobayashi, Takashi; Adachi, Shuji

    2016-05-01

    Isomerization of disaccharides (maltose, isomaltose, cellobiose, lactose, melibiose, palatinose, sucrose, and trehalose) was investigated in subcritical aqueous ethanol. A marked increase in the isomerization of aldo-disaccharides to keto-disaccharides was noted and their hydrolytic reactions were suppressed with increasing ethanol concentration. Under any study condition, the maximum yield of keto-disaccharides produced from aldo-disaccharides linked by β-glycosidic bond was higher than that produced from aldo-disaccharides linked by α-glycosidic bond. Palatinose, a keto-disaccharide, mainly underwent decomposition rather than isomerization in subcritical water and subcritical aqueous ethanol. No isomerization was noted for the non-reducing disaccharides trehalose and sucrose. The rate constant of maltose to maltulose isomerization almost doubled by changing solvent from subcritical water to 80 wt% aqueous ethanol at 220 °C. Increased maltose monohydrate concentration in feed decreased the conversion of maltose and the maximum yield of maltulose, but increased the productivity of maltulose. The maximum productivity of maltulose was ca. 41 g/(h kg-solution).

  19. Understanding the Aldo-Enediolate Tautomerism of Glycolaldehyde in Basic Aqueous Solutions.

    PubMed

    Azofra, Luis Miguel; Quesada-Moreno, María Mar; Alkorta, Ibon; Avilés-Moreno, Juan Ramón; Elguero, José; López-González, Juan Jesús

    2015-07-20

    The biochemically important interconversion process between aldoses and ketoses is assumed to take place via 1,2-enediol or 1,2-enediolate intermediates, but such intermediates have never been isolated. The current work was undertaken in an attempt to detect the presence of the 1,2-enediol structure of glycolaldehyde in alkaline medium, actually a 1,2-enediolate, and to try to clarify the scarce data existing about both the formation of deprotonated enediol and the aldo-enediolate equilibrium. The Raman spectra of neutral and basic solutions were recorded as a function of time for eleven days. Several bands associated with the presence of the enediolate were observed in alkaline medium. Glycolaldehyde exists as three different structures in aqueous solution at neutral pH, that is, hydrated aldehydes, aldehydes and dimers, with a respective ratio of approximately 4:0.25:1. Additionally, the formation of Z-enediolate forms takes place at basic pH, together with an increase in the concentration of aldehyde species, such as 2-oxoethan-1-olate, and a decrease in the concentrations of the hydrated aldehyde and dimeric forms. The theoretical ratio of ≈1.5:1 for aldehyde:Z-enediolate reproduces the experimental Raman spectrum in basic medium, with an additional contribution of the previously mentioned ratio between the hydrated aldehyde and dimeric forms. Finally, Raman spectroscopy allowed us to monitor the enolization of this carbohydrate model and conclude that aldo-enediol tautomerism-formally aldo-enediolate-happens when a suitable amount of basic species is added.

  20. The Aldo-Keto Reductase Superfamily and its Role in Drug Metabolism and Detoxification

    PubMed Central

    Barski, Oleg A.; Tipparaju, Srinivas M.; Bhatnagar, Aruni

    2008-01-01

    The Aldo-Keto Reductase (AKR) superfamily comprises of several enzymes that catalyze redox transformations involved in biosynthesis, intermediary metabolism and detoxification. Substrates of the family include glucose, steroids, glycosylation end products, lipid peroxidation products, and environmental pollutants. These proteins adopt a (β/α)8 barrel structural motif interrupted by a number of extraneous loops and helixes that vary between proteins and bring structural identity to individual families. The human AKR family differs from the rodent families. Due to their broad substrate specificity, AKRs play an important role in the Phase II detoxification of a large number of pharmaceuticals, drugs, and xenobiotics. PMID:18949601

  1. Beam imaging in the injection line of the INFN-LNS superconducting cyclotron

    NASA Astrophysics Data System (ADS)

    Nicolosi, Dario; Cosentino, Luigi; Mascali, David; Pappalardo, Alfio; Castro, Maurizio; Celona, Luigi; Marchetta, Carmelo; Marletta, Salvatore; Maugeri, Antonio; Rifuggiato, Danilo; Seminara, Angelo; Gammino, Santo

    2016-02-01

    A cheap and efficient diagnostic system for beam monitoring has been recently developed at INFN-LNS in Catania. It consists of a high sensitivity CCD camera detecting the light produced by an ion beam hitting the surface of a scintillating screen and a frame grabber for image acquisition. A scintillating screen, developed at INFN-LNS and consisting of a 2 μm BaF2 layer evaporated on an aluminium plate, has been tested by using 20Ne and 40Ar beams in the keV energy range. The CAESAR ECR ion source has been used for investigating the influence of the frequency and magnetic field tuning effects, the impact of the microwave injected power, and of the focusing solenoids along the low energy beam transport on the beam shape and current. These tests will allow to better understand the interplay between the plasma and beam dynamics and, moreover, to improve the transport efficiency along the low energy beam line and the matching with the superconducting cyclotron, particularly relevant in view of the expected upgrade of the machine.

  2. Beam imaging in the injection line of the INFN-LNS superconducting cyclotron.

    PubMed

    Nicolosi, Dario; Cosentino, Luigi; Mascali, David; Pappalardo, Alfio; Castro, Maurizio; Celona, Luigi; Marchetta, Carmelo; Marletta, Salvatore; Maugeri, Antonio; Rifuggiato, Danilo; Seminara, Angelo; Gammino, Santo

    2016-02-01

    A cheap and efficient diagnostic system for beam monitoring has been recently developed at INFN-LNS in Catania. It consists of a high sensitivity CCD camera detecting the light produced by an ion beam hitting the surface of a scintillating screen and a frame grabber for image acquisition. A scintillating screen, developed at INFN-LNS and consisting of a 2 μm BaF2 layer evaporated on an aluminium plate, has been tested by using (20)Ne and (40)Ar beams in the keV energy range. The CAESAR ECR ion source has been used for investigating the influence of the frequency and magnetic field tuning effects, the impact of the microwave injected power, and of the focusing solenoids along the low energy beam transport on the beam shape and current. These tests will allow to better understand the interplay between the plasma and beam dynamics and, moreover, to improve the transport efficiency along the low energy beam line and the matching with the superconducting cyclotron, particularly relevant in view of the expected upgrade of the machine.

  3. Aldo Leopold on Education: An Educator and His Land Ethic in the Context of Contemporary Environmental Education.

    ERIC Educational Resources Information Center

    Callicott, J. Baird

    1982-01-01

    Aldo Leopold, the founder of wildlife management (wildlife ecology) is credited with powerfully advocating for the first time in Western intellectual history, broad human ethical responsibility to the nonhuman natural world. Leopold's views on education and Leopold as an educator are discussed. (Author/JN)

  4. Cryogenic Control System Migration and Developments towards the UNICOS CERN Standard at INFN

    NASA Astrophysics Data System (ADS)

    Modanese, Paolo; Calore, Andrea; Contran, Tiziano; Friso, Alessandro; Pengo, Marco; Canella, Stefania; Burioli, Sergio; Gallese, Benedetto; Inglese, Vitaliano; Pezzetti, Marco; Pengo, Ruggero

    The cryogenic control systems at Laboratori Nazionali di Legnaro (LNL) are undergoing an important and radical modernization, allowing all the plants controls and supervision systems to be renewed in a homogeneous way towards the CERN-UNICOS standard. Before the UNICOS migration project started there were as many as 7 different types of PLC and 7 different types of SCADA, each one requiring its own particular programming language. In these conditions, even a simple modification and/or integration on the program or on the supervision, required the intervention of a system integrator company, specialized in its specific control system. Furthermore it implied that the operators have to be trained to learn the different types of control systems. The CERN-UNICOS invented for LHC [1] has been chosen due to its reliability and planned to run and be maintained for decades on. The complete migration is part of an agreement between CERN and INFN.

  5. Towards the final BSA modeling for the accelerator-driven BNCT facility at INFN LNL.

    PubMed

    Ceballos, C; Esposito, J; Agosteo, S; Colautti, P; Conte, V; Moro, D; Pola, A

    2011-12-01

    Some remarkable advances have been made in the last years on the SPES-BNCT project of the Istituto Nazionale di Fisica Nucleare (INFN) towards the development of the accelerator-driven thermal neutron beam facility at the Legnaro National Laboratories (LNL), aimed at the BNCT experimental treatment of extended skin melanoma. The compact neutron source will be produced via the (9)Be(p,xn) reactions using the 5 MeV, 30 mA beam driven by the RFQ accelerator, whose modules construction has been recently completed, into a thick beryllium target prototype already available. The Beam Shaping Assembly (BSA) final modeling, using both neutron converter and the new, detailed, Be(p,xn) neutron yield spectra at 5 MeV energy recently measured at the CN Van de Graaff accelerator at LNL, is summarized here.

  6. First beam from the TRASCO intense proton source (TRIPS) at INFN-LNS

    NASA Astrophysics Data System (ADS)

    Ciavola, G.; Celona, L.; Gammino, S.; Chines, F.; Campisano, C.

    2002-02-01

    The TRASCO intense proton source (TRIPS) was installed at INFN-LNS in May 2000 and the commissioning is in progress. This article describes the design of the source along with the first results and the next developments. The source has been able to deliver more than 20 mA of protons with high reliability from a 4.5 mm extraction aperture at 65 kV, largely above the minimum requested current density. The goals in terms of beam energy (80 keV) and current (60 mA from 8 mm extraction aperture) have been achieved. Further optimization of the source is under way, with special care given to the reliability needed for the accelerator driving system purpose.

  7. The INFN-CNAF Tier-1 GEMSS Mass Storage System and database facility activity

    NASA Astrophysics Data System (ADS)

    Ricci, Pier Paolo; Cavalli, Alessandro; Dell'Agnello, Luca; Favaro, Matteo; Gregori, Daniele; Prosperini, Andrea; Pezzi, Michele; Sapunenko, Vladimir; Zizzi, Giovanni; Vagnoni, Vincenzo

    2015-05-01

    The consolidation of Mass Storage services at the INFN-CNAF Tier1 Storage department that has occurred during the last 5 years, resulted in a reliable, high performance and moderately easy-to-manage facility that provides data access, archive, backup and database services to several different use cases. At present, the GEMSS Mass Storage System, developed and installed at CNAF and based upon an integration between the IBM GPFS parallel filesystem and the Tivoli Storage Manager (TSM) tape management software, is one of the largest hierarchical storage sites in Europe. It provides storage resources for about 12% of LHC data, as well as for data of other non-LHC experiments. Files are accessed using standard SRM Grid services provided by the Storage Resource Manager (StoRM), also developed at CNAF. Data access is also provided by XRootD and HTTP/WebDaV endpoints. Besides these services, an Oracle database facility is in production characterized by an effective level of parallelism, redundancy and availability. This facility is running databases for storing and accessing relational data objects and for providing database services to the currently active use cases. It takes advantage of several Oracle technologies, like Real Application Cluster (RAC), Automatic Storage Manager (ASM) and Enterprise Manager centralized management tools, together with other technologies for performance optimization, ease of management and downtime reduction. The aim of the present paper is to illustrate the state-of-the-art of the INFN-CNAF Tier1 Storage department infrastructures and software services, and to give a brief outlook to forthcoming projects. A description of the administrative, monitoring and problem-tracking tools that play a primary role in managing the whole storage framework is also given.

  8. Lignases and aldo-keto reductases for conversion of lignin-containing materials to fermentable products

    DOEpatents

    Scharf, Michael; Sethi, Amit

    2016-09-13

    Termites have specialized digestive systems that overcome the lignin barrier in wood to release fermentable simple sugars. Using the termite Reticulitermes flavipes and its gut symbionts, high-throughput titanium pyrosequencing and proteomics approaches experimentally compared the effects of lignin-containing diets on host-symbiont digestome composition. Proteomic investigations and functional digestive studies with recombinant lignocellulases conducted in parallel provided strong evidence of congruence at the transcription and translational levels and provide enzymatic strategies for overcoming recalcitrant lignin barriers in biofuel feedstocks. Briefly described, therefore, the disclosure provides a system for generating a fermentable product from a lignified plant material, the system comprising a cooperating series of at least two catalytically active polypeptides, where said catalytically active polypeptides are selected from the group consisting of: cellulase Cell-1, .beta.-glu cellulase, an aldo-keto-reductase, a catalase, a laccase, and an endo-xylanase.

  9. Berberine inhibits androgen synthesis by interaction with aldo-keto reductase 1C3 in 22Rv1 prostate cancer cells.

    PubMed

    Tian, Yuantong; Zhao, Lijing; Wang, Ye; Zhang, Haitao; Xu, Duo; Zhao, Xuejian; Li, Yi; Li, Jing

    2016-01-01

    Aldo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aldo-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form p-p interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound.

  10. The SPES project at the INFN-Laboratori Nazionali di Legnaro

    NASA Astrophysics Data System (ADS)

    Prete, G.

    2016-11-01

    The SPES Radioactive Ion Beam (RIB) facility is in the construction phase at INFN-LNL. It is based on a dual exit high current Cyclotron, with tunable proton beam energy 35-70MeV and 0.2-0.5mA, used as proton driver to supply an ISOL system with an UCx Direct Target able to sustain a power of 10kW. The second exit will be used for applied physics: radioisotope production for medicine and neutrons for material study. The ISOL system will produce neutron-rich radioactive ions by proton induced fission in the UCx target. The expected fission rate in the target is in the order of 1013 fissions per second. The exotic isotopes will be re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses around A = 130 amu , with an expected beam intensity around 107-109 pps . Fast neutron spectra will be produced by the proton beam interaction with a conversion target. A production rate in excess of 1014 n/s is expected. The SPES project has the aim to provide high intensity and high-quality beams of neutron-rich nuclei as well as to develop an interdisciplinary research center based on the cyclotron proton beam. The status of the project will be presented.

  11. X-band accelerator structures: On going R&D at the INFN

    NASA Astrophysics Data System (ADS)

    Gatti, G.; Marcelli, A.; Spataro, B.; Dolgashev, V.; Lewandowski, J.; Tantawi, S. G.; Yeremian, A. D.; Higashi, Y.; Rosenzweig, J.; Sarti, S.; Caliendo, C.; Castorina, G.; Cibin, G.; Carfora, L.; Leonardi, O.; Rigato, V.; Campostrini, M.

    2016-09-01

    The next generation of accelerators, from the compact to the large infrastructure dedicated to high energy physics, is highly demanding in terms of accelerating gradients. To upgrade performances of X band linacs at 11.424 GHz many resources are devoted to achieve high accelerating gradients and at the same time to obtain a high reliability. In the framework of a three-year funded project by the Vth Committee of the INFN to the Laboratori Nazionali di Frascati (LNF) and to the Laboratori Nazionali di Legnaro (LNL). Within a broad international collaboration the LNF has been involved in the design, manufacture and test of compact high power standing wave (SW) sections operating at high frequency while LNL is actively involved in the development of new materials and multilayers using PVD (Physical Vapor Deposition) methods. We will report about the status of the accelerating device and of the different ongoing R&D activities and characterization procedures such as tests of different materials and metallic coatings.

  12. MEG II drift chamber characterization with the silicon based cosmic ray tracker at INFN Pisa

    NASA Astrophysics Data System (ADS)

    Venturini, M.; Baldini, A. M.; Baracchini, E.; Cei, F.; D`Onofrio, A.; Dussoni, S.; Galli, L.; Grassi, M.; Nicolò, D.; Signorelli, G.

    2016-07-01

    High energy physics experiments at the high intensity frontier place ever greater demands on detectors, and in particular on tracking devices. In order to compare the performance of small size tracking prototypes, a high resolution cosmic ray tracker has been assembled to provide an external track reference. It consists of four spare ladders of the external layers of the Silicon Vertex Tracker of the BaBar experiment. The test facility, operating at INFN Sezione di Pisa, provides the detector under test with an external track with an intrinsic resolution of 15-30 μm. The MEG II tracker is conceived as a unique volume wire drift chamber filled with He-isobutane 85-15%. The ionization density in this gas mixture is about 13 clusters/cm and this results in a non-negligible bias of the impact parameters for tracks crossing the cell close to the anode wire. We present the telescope performance in terms of tracking efficiency and resolution and the results of the characterization of a MEG II drift chamber prototype.

  13. The Injection System of the INFN-SuperB Factory Project: Preliminary Design

    SciTech Connect

    Boni, Roberto; Guiducci, Susanna; Preger, Miro; Raimondi, Pantaleo; Chance, Antoine; Dadoun, Olivier; Poirier, Freddy; Variola, Alessandro; Seeman, John; /SLAC

    2012-07-05

    The ultra high luminosity B-factory (SuperB) project of INFN requires a high performance and reliable injection system, providing electrons at 4 GeV and positrons at 7 GeV, to fulfil the very tight requirements of the collider. Due to the short beam lifetime, continuous injection of electron and positron bunches in both LER and HER rings is necessary to maintain an high average luminosity. Polarized electrons are required for experiments and must be delivered by the injection system, due to the beam lifetime shorter than the ring polarization build-up: they will be produced by means of a SLAC-SLC polarized gun. The emittance and the energy spread of the e{sup -}/e{sup +} beams are reduced in a 1 GeV Damping Ring (DR) before injection in the main rings. Two schemes for positron production are under study, one with e{sup -}/e{sup +} conversion at low energy (< 1 Gev) and one with conversion at 6 GeV and a recirculation line to bring the positrons back to the DR. Acceleration through the Linac is provided by a 2856 MHz RF system made of travelling wave (TW), room temperature accelerating structures.

  14. Progress in the design and construction of SPES at INFN-LNL

    NASA Astrophysics Data System (ADS)

    Bisoffi, G.; Prete, G.; Andrighetto, A.; Andreev, V.; Bellan, L.; Bellato, M.; Bortolato, D.; Calderolla, M.; Canella, S.; Comunian, M.; Corradetti, S.; Fagotti, E.; Facco, A.; Favaron, P.; Ferrari, L.; Galatà, A.; Giacchini, M.; Gramegna, F.; Gulmini, M.; Lombardi, A.; Maggiore, M.; Manzolaro, M.; Modanese, P.; Moisio, M. F.; Monetti, A.; Palmieri, A.; Pisent, A.; Poggi, M.; Porcellato, A. M.; Rossignoli, M.; Roncolato, C.; Russo, A.; Sarchiapone, L.; Scarpa, D.; Vasquez, J.; Zafiropoulos, D.

    2016-06-01

    INFN-LNL is constructing an ISOL (Isotope Separation On Line) facility delivering neutron rich ion beams at 10 A MeV or beyond, making use of the linear accelerator ALPI as the secondary accelerator. The facility includes a direct ISOL target based on UCx and able to reach 1013 fissions/s. In parallel, an applied physics facility will be developed, with applications in medicine and neutron production. The SPES project is a national facility, approved and funded. Commissioning with the first exotic species is expected in 2019. The primary accelerator is a commercial cyclotron, which will send a 40 MeV, 200 μA proton beam onto an UCx target, connected to SIS, PIS and LIS ion sources. The extracted beam is purified through a Low Resolution Mass Separator (LMRS, i.e. a Wien filter and a dispersive dipole), a beam cooler and a High Resolution Mass Separator (HRMS) and sent to an ECR charge breeder to boost the exotic beam charge state. The highly charged exotic beam is further separated in a MRMS (Medium Resolution Mass Separator) and injected into a 100% duty cycle RFQ and into the existing superconducting linac ALPI, which will be refurbished and upgraded to be an efficient exotic beam accelerator. The upgrade of ALPI will give ∼10 A MeV energy to 132Sn19+, taken as the reference ion beam. The paper presents the status of the design and construction of the SPES facility.

  15. The nuclear matrix elements of 0vββ decay and the NUMEN project at INFN-LNS

    NASA Astrophysics Data System (ADS)

    Cappuzzello, F.; Agodi, C.; Aciksoz, E.; Acosta, L.; Aslanouglou, X.; Auerbach, N.; Bijker, R.; Bonanno, D.; Bongiovanni, D.; Borello, T.; Boudhaim, S.; Bouhssa, M. L.; Boztosun, I.; Calabretta, L.; Calanna, A.; Carbone, D.; Cavallaro, M.; Calvo, D.; Chávez Lomelí, E. R.; Colonna, M.; D'Agostino, G.; Deshmukh, N.; de Faria, P. N.; Ferrero, A.; Foti, A.; Finocchiaro, P.; Gomes, P. R. S.; Greco, V.; Hacisalihoglu, A.; Housni, Z.; Khouaja, A.; Inchaou, J.; Lanzalone, G.; La Via, F.; Lay, J. A.; Lenske, H.; Linares, R.; Lubian, J.; Iazzi, F.; Introzzi, R.; Lavagno, A.; Lo Presti, D.; Medina, N.; Mendes, D. R.; Muoio, A.; Oliveira, J. R. B.; Pakou, A.; Pandola, L.; Rifuggiato, D.; Rodrigues, M. R. D.; Santagati, G.; Santopinto, E.; Scaltrito, L.; Sgouros, O.; Solakcı, S. O.; Soukeras, V.; Tudisco, S.; Vsevolodovna, R. I. M.; Zagatto, V.

    2016-07-01

    An innovative technique to access the nuclear matrix elements entering the expression of the life time of the double beta decay by relevant cross section measurements of double charge exchange reactions is proposed. A key aspect of the project is the use of the MAGNEX large acceptance magnetic spectrometer, for the detection of the ejectiles, and of the LNS K800 Superconducting Cyclotron (CS), for the acceleration of the required high resolution and low emittance heavy-ion beams, already in operation at INFN Laboratory Nazionali del Sud in Catania (Italy). However, a major upgrade is foreseen for the INFN-LNS research infrastructure to cope with beam currents as high as several ppA required by the project.

  16. Cloning and characterization of a NADH-dependent aldo-keto reductase from a newly isolated Kluyveromyces lactis XP1461.

    PubMed

    Luo, Xi; Wang, Ya-Jun; Zheng, Yu-Guo

    2015-09-01

    An aldo-keto reductase gene (klakr) from Kluyveromyces lactis XP1461 was cloned and heterologously expressed in Escherichia coli. The aldo-keto reductase KlAKR was purified and found to be NADH-dependent with a molecular weight of approximately 36 kDa. It is active and stable at 30 °C and pH 7.0. The maximal reaction rate (vmax), apparent Michaelis-Menten constant (Km) for NADH and t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate (1a) and catalytic number (kcat) were calculated as 7.63 U mg(-1), 0.204 mM, 4.42 mM and 697.4 min(-1), respectively. Moreover, the KlAKR has broad substrate specificity to a range of aldehydes, ketones and keto-esters, producing chiral alcohol with e.e. or d.e. >99% for the majority of test substrates.

  17. Use of 70 MeV proton beam for medical applications at INFN-LNS: CATANA project

    NASA Astrophysics Data System (ADS)

    Sabini, M. G.; Cirrone, G. A. P.; Tonghi, L. Barone; Bartolotta, A.; Brai, M.; Cuttone, G.; Nigro, S. Lo; Marano, F.; Nicoletti, G. A.; Privitera, G.; Raffaele, L.; Reibaldi, A.; Romeo, N.; Rovelli, A.; Salamone, V.; Teri, G.

    2000-04-01

    The project CATANA (Centro di Adro Terapia ed Applicazioni Nucleari Avanzate) is a collaboration between the INFN-Laboratori Nazionali del Sud (LNS), Physics Department, Ophthalmology Institute and Radiology Institute of the Catania University and CSFNSM Catania. The main goal of CATANA is the study and the application of protontherapy for the treatment of shallow tumors (4 cm max) like uveal melanomas and subfoveal macular degenerations.

  18. A self-configuring control system for storage and computing departments at INFN-CNAF Tierl

    NASA Astrophysics Data System (ADS)

    Gregori, Daniele; Dal Pra, Stefano; Ricci, Pier Paolo; Pezzi, Michele; Prosperini, Andrea; Sapunenko, Vladimir

    2015-05-01

    The storage and farming departments at the INFN-CNAF Tier1[1] manage approximately thousands of computing nodes and several hundreds of servers that provides access to the disk and tape storage. In particular, the storage server machines should provide the following services: an efficient access to about 15 petabytes of disk space with different cluster of GPFS file system, the data transfers between LHC Tiers sites (Tier0, Tier1 and Tier2) via GridFTP cluster and Xrootd protocol and finally the writing and reading data operations on magnetic tape backend. One of the most important and essential point in order to get a reliable service is a control system that can warn if problems arise and which is able to perform automatic recovery operations in case of service interruptions or major failures. Moreover, during daily operations the configurations can change, i.e. if the GPFS cluster nodes roles can be modified and therefore the obsolete nodes must be removed from the control system production, and the new servers should be added to the ones that are already present. The manual management of all these changes is an operation that can be somewhat difficult in case of several changes, it can also take a long time and is easily subject to human error or misconfiguration. For these reasons we have developed a control system with the feature of self-configure itself if any change occurs. Currently, this system has been in production for about a year at the INFN-CNAF Tier1 with good results and hardly any major drawback. There are three major key points in this system. The first is a software configurator service (e.g. Quattor or Puppet) for the servers machines that we want to monitor with the control system; this service must ensure the presence of appropriate sensors and custom scripts on the nodes to check and should be able to install and update software packages on them. The second key element is a database containing information, according to a suitable format, on

  19. Xrootd data access for LHC experiments at the INFN-CNAF Tier-1

    NASA Astrophysics Data System (ADS)

    Gregori, Daniele; Boccali, Tommaso; Noferini, Francesco; Prosperini, Andrea; Ricci, Pier Paolo; Sapunenko, Vladimir; Vagnoni, Vincenzo

    2014-06-01

    The Mass Storage System installed at the INFN-CNAF Tier-1 is one of the biggest hierarchical storage facilities in Europe. It currently provides storage resources for about 12% of all LHC data, as well as for other experiments. The Grid Enabled Mass Storage System (GEMSS) is the current solution implemented at CNAF and it is based on a custom integration between a high performance parallel file system (General Parallel File System, GPFS) and a tape management system for long-term storage on magnetic media (Tivoli Storage Manager, TSM). Data access to Grid users is being granted since several years by the Storage Resource Manager (StoRM), an implementation of the standard SRM interface, widely adopted within the WLCG community. The evolving requirements from the LHC experiments and other users are leading to the adoption of more flexible methods for accessing the storage. These include the implementation of the so-called storage federations, i.e. geographically distributed federations allowing direct file access to the federated storage between sites. A specific integration between GEMSS and Xrootd has been developed at CNAF to match the requirements of the CMS experiment. This was already implemented for the ALICE use case, using ad-hoc Xrootd modifications. The new developments for CMS have been validated and are already available in the official Xrootd builds. This integration is currently in production and appropriate large scale tests have been made. In this paper we present the Xrootd solutions adopted for ALICE, CMS, ATLAS and LHCb to increase the availability and optimize the overall performance.

  20. Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism.

    PubMed

    Rižner, Tea Lanišnik; Penning, Trevor M

    2014-01-01

    Human aldo-keto reductases AKR1C1-AKR1C4 and AKR1D1 play essential roles in the metabolism of all steroid hormones, the biosynthesis of neurosteroids and bile acids, the metabolism of conjugated steroids, and synthetic therapeutic steroids. These enzymes catalyze NADPH dependent reductions at the C3, C5, C17 and C20 positions on the steroid nucleus and side-chain. AKR1C1-AKR1C4 act as 3-keto, 17-keto and 20-ketosteroid reductases to varying extents, while AKR1D1 acts as the sole Δ(4)-3-ketosteroid-5β-reductase (steroid 5β-reductase) in humans. AKR1 enzymes control the concentrations of active ligands for nuclear receptors and control their ligand occupancy and trans-activation, they also regulate the amount of neurosteroids that can modulate the activity of GABAA and NMDA receptors. As such they are involved in the pre-receptor regulation of nuclear and membrane bound receptors. Altered expression of individual AKR1C genes is related to development of prostate, breast, and endometrial cancer. Mutations in AKR1C1 and AKR1C4 are responsible for sexual development dysgenesis and mutations in AKR1D1 are causative in bile-acid deficiency.

  1. Roles of rat and human aldo-keto reductases in metabolism of farnesol and geranylgeraniol

    PubMed Central

    Endo, Satoshi; Matsunaga, Toshiyuki; Ohta, Chisato; Soda, Midori; Kanamori, Ayano; Kitade, Yukio; Ohno, Satoshi; Tajima, Kazuo; El-Kabbani, Ossama; Hara, Akira

    2011-01-01

    Farnesol (FOH) and geranylgeraniol (GGOH) with multiple biological actions are produced from the mevalonate pathway, and catabolized into farnesoic acid and geranylgeranoic acid, respectively, via the aldehyde intermediates (farnesal and geranylgeranial). We investigated the intracellular distribution, sequences and properties of the oxidoreductases responsible for the metabolic steps in rat tissues. The oxidation of FOH and GGOH into their aldehyde intermediates were mainly mediated by alcohol dehydrogenases 1 (in the liver and colon) and 7 (in the stomach and lung), and the subsequent step into the carboxylic acids was catalyzed by a microsomal aldehyde dehydrogenase. In addition, high reductase activity catalyzing the aldehyde intermediates into FOH (or GGOH) was detected in the cytosols of the extra-hepatic tissues, where the major reductase was identified as aldo-keto reductase (AKR) 1C15. Human reductases with similar specificity were identified as AKR1B10 and AKR1C3, which most efficiently reduced farnesal and geranylgeranial among seven enzymes in the AKR1A-1C subfamilies. The overall metabolism from FOH to farnesoic acid in cultured cells was significantly decreased by overexpression of AKR1C15, and increased by addition of AKR1C3 inhibitors, tolfenamic acid and R-flurbiprofen. Thus, AKRs (1C15 in rats, and 1B10 and 1C3 in humans) may play an important role in controlling the bioavailability of FOH and GGOH. PMID:21187079

  2. Effect of thermal stability on protein adsorption to silica using homologous aldo-keto reductases

    PubMed Central

    Felsovalyi, Flora; Patel, Tushar; Mangiagalli, Paolo; Kumar, Sanat K; Banta, Scott

    2012-01-01

    Gaining more insight into the mechanisms governing the behavior of proteins at solid/liquid interfaces is particularly relevant in the interaction of high-value biologics with storage and delivery device surfaces, where adsorption-induced conformational changes may dramatically affect biocompatibility. The impact of structural stability on interfacial behavior has been previously investigated by engineering nonwild-type stability mutants. Potential shortcomings of such approaches include only modest changes in thermostability, and the introduction of changes in the topology of the proteins when disulfide bonds are incorporated. Here we employ two members of the aldo-keto reductase superfamily (alcohol dehydrogenase, AdhD and human aldose reductase, hAR) to gain a new perspective on the role of naturally occurring thermostability on adsorbed protein arrangement and its subsequent impact on desorption. Unexpectedly, we find that during initial adsorption events, both proteins have similar affinity to the substrate and undergo nearly identical levels of structural perturbation. Interesting differences between AdhD and hAR occur during desorption and both proteins exhibit some level of activity loss and irreversible conformational change upon desorption. Although such surface-induced denaturation is expected for the less stable hAR, it is remarkable that the extremely thermostable AdhD is similarly affected by adsorption-induced events. These results question the role of thermal stability as a predictor of protein adsorption/desorption behavior. PMID:22619179

  3. Activity improvement of a Kluyveromyces lactis aldo-keto reductase KlAKR via rational design.

    PubMed

    Luo, Xi; Wang, Ya-Jun; Shen, Wei; Zheng, Yu-Guo

    2016-04-20

    Optically pure t-butyl 6-cyano-(3R, 5R)-dihydroxyhexanoate ((R)-1b) is the key chiral precursor for atorvastatin calcium, the most widely used cholesterol-lowering drug. Wild-type aldo-keto reductase KlAKR from Kluyveromyces lactis has ideal diastereoselectivity toward t-butyl 6-cyano-(5R)-hydroxy-3-oxohexanoate (1a, dep>99.5%) but poor activity. A rational engineering was used to improve the KlAKR activity. Based on homology modeling and molecular docking, two amino acid residues (295 and 296) were selected as mutation sites, and two rounds of site-saturation mutagenesis were performed. Among the mutants, KlAKR-Y295W/W296L exhibited the highest catalytic efficiency (kcat/Km) toward 1a up to 12.37s(-1)mM(-1), which was 11.25-fold higher than that of wild-type KlAKR. Moreover, the majority of mutations have no negative impact on stereoselectivity. Using KlAKR-Y295W/W296L coupled with Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) for cofactor regeneration, (R)-1b was accumulated up to 162.7mM with dep value above 99.5%. KlAKR-Y295W/W296L represents a robust tool for (R)-1b synthesis.

  4. The charge breeder beam line for the selective production of exotic species project at INFN-Legnaro National Laboratories

    NASA Astrophysics Data System (ADS)

    Galatà, A.; Comunian, M.; Maggiore, M.; Manzolaro, M.; Angot, J.; Lamy, T.

    2014-02-01

    SPES (Selective Production of Exotic Species) is an INFN (Istituto Nazionale di Fisica Nucleare) project with the aim at producing and post-accelerating exotic beams to perform forefront research in nuclear physics. To allow post-acceleration of the radioactive ions, an ECR-based Charge Breeder (CB) developed on the basis of the Phoenix booster was chosen. The design of the complete beam line for the SPES-CB will be described: a system for stable 1+ beams production was included; special attention was paid to the medium resolution mass spectrometer after the CB to limit possible superposition of the exotic beams with the impurities present in the ECR plasma.

  5. Inter-comparison of boron concentration measurements at INFN-University of Pavia (Italy) and CNEA (Argentina).

    PubMed

    Portu, Agustina; Postuma, Ian; Gadan, Mario Alberto; Saint Martin, Gisela; Olivera, María Silvina; Altieri, Saverio; Protti, Nicoletta; Bortolussi, Silva

    2015-11-01

    An inter-comparison of three boron determination techniques was carried out between laboratories from INFN-University of Pavia (Italy) and CNEA (Argentina): alpha spectrometry (alpha-spect), neutron capture radiography (NCR) and quantitative autoradiography (QTA). Samples of different nature were analysed: liquid standards, liver homogenates and tissue samples from different treatment protocols. The techniques showed a good agreement in a concentration range of interest in BNCT (1-100ppm), thus demonstrating their applicability as precise methods to quantify boron and determine its distribution in tissues.

  6. Aldo-keto reductases in retinoid metabolism: search for substrate specificity and inhibitor selectivity.

    PubMed

    Porté, Sergio; Xavier Ruiz, F; Giménez, Joan; Molist, Iago; Alvarez, Susana; Domínguez, Marta; Alvarez, Rosana; de Lera, Angel R; Parés, Xavier; Farrés, Jaume

    2013-02-25

    Biological activity of natural retinoids requires the oxidation of retinol to retinoic acid (RA) and its binding to specific nuclear receptors in target tissues. The first step of this pathway, the reversible oxidoreduction of retinol to retinaldehyde, is essential to control RA levels. The enzymes of retinol oxidation are NAD-dependent dehydrogenases of the cytosolic medium-chain (MDR) and the membrane-bound short-chain (SDR) dehydrogenases/reductases. Retinaldehyde reduction can be performed by SDR and aldo-keto reductases (AKR), while its oxidation to RA is carried out by aldehyde dehydrogenases (ALDH). In contrast to SDR, AKR and ALDH are cytosolic. A common property of these enzymes is that they only use free retinoid, but not retinoid bound to cellular retinol binding protein (CRBP). The relative contribution of each enzyme type in retinoid metabolism is discussed in terms of the different subcellular localization, topology of membrane-bound enzymes, kinetic constants, binding affinity of CRBP for retinol and retinaldehyde, and partition of retinoid pools between membranes and cytoplasm. The development of selective inhibitors for AKR enzymes 1B1 and 1B10, of clinical relevance in diabetes and cancer, granted the investigation of some structure-activity relationships. Kinetics with the 4-methyl derivatives of retinaldehyde isomers was performed to identify structural features for substrate specificity. Hydrophilic derivatives were better substrates than the more hydrophobic compounds. We also explored the inhibitory properties of some synthetic retinoids, known for binding to retinoic acid receptors (RAR) and retinoid X receptors (RXR). Consistent with its substrate specificity towards retinaldehyde, AKR1B10 was more effectively inhibited by synthetic retinoids than AKR1B1. A RARβ/γ agonist (UVI2008) inhibited AKR1B10 with the highest potency and selectivity, and docking simulations predicted that its carboxyl group binds to the anion-binding pocket. PMID

  7. 9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant.

    PubMed

    Matsunaga, Toshiyuki; Haga, Mariko; Watanabe, Gou; Shinoda, Yuhki; Endo, Satoshi; Kajiwara, Yu; Tanaka, Hiroyuki; Inagaki, Naoki; El-Kabbani, Ossama; Hara, Akira

    2012-02-01

    9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, induces apoptosis via the generation of reactive oxygen species (ROS) because of 9,10-PQ redox cycling. We have found that intratracheal infusion of 9,10-PQ facilitates the secretion of surfactant into rat alveolus. In the cultured rat lung, treatment with 9,10-PQ results in an increase in a lower-density surfactant by ROS generation through redox cycling of the quinone. The surfactant contains aldo-keto reductase (AKR) 1C15, which reduces 9,10-PQ and the enzyme level in the surfactant increases on treatment with 9,10-PQ suggesting an involvement of AKR1C15 in the redox cycling of the quinone. In six human cell types (A549, MKN45, Caco2, Hela, Molt4 and U937) only type II epithelial A549 cells secrete three human AKR1C subfamily members (AKR1C1, AKR1C2 and AKR1C3) with the surfactant into the medium; this secretion is highly increased by 9,10-PQ treatment. Using in vitro enzyme inhibition analysis, we have identified AKR1C3 as the most abundantly secreted AKR1C member. The AKR1C enzymes in the medium efficiently reduce 9,10-PQ and initiate its redox cycling accompanied by ROS production. The exposure of A549 cells to 9,10-PQ provokes viability loss, which is significantly protected by the addition of the AKR1C3 inhibitor and antioxidant enzyme and by the removal of the surfactants from the culture medium. Thus, the AKR1C enzymes secreted in pulmonary surfactants probably participate in the toxic mechanism triggered by 9,10-PQ.

  8. Human aldo-keto reductases and the metabolic activation of polycyclic aromatic hydrocarbons.

    PubMed

    Penning, Trevor M

    2014-11-17

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1-AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2'-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer.

  9. Alternative splicing in the aldo-keto reductase superfamily: implications for protein nomenclature.

    PubMed

    Barski, Oleg A; Mindnich, Rebekka; Penning, Trevor M

    2013-02-25

    The aldo-keto reductase superfamily contains 173 proteins which are present in all phyla. Examination of the human and mouse genomes has identified that in some instances a single AKR gene can give rise to alternatively spliced mRNA variants which in some cases can give rise to more than one protein isoform. This is currently well documented in the AKR6A subfamily which contains the β-subunits of the voltage-gated potassium ion channels. With the emergence of second generation sequencing it is likely that the occurrence of transcript variants and protein isoforms from a single AKR gene may become common place. To deal with this issue we recommend that the Ensembl data-base nomenclature be used to annotate the transcript variants from a single AKR gene. However, since multiple transcript variants could give rise to either the same or multiple protein isoforms from the same AKR gene we also propose to expand the nomenclature of the AKR protein superfamily, so that when a protein isoform is shown to be expressed and is functional it would be assigned the standard AKR name followed by a "period or full-stop" and a number for that unique isoform. Numbers will be assigned chronologically and linked to the respective transcripts annotated in Ensembl e.g. AKR6A5.1 (Kvβ2.1) (AKR6A5-001, -006 and -201), followed by AKR6A5.2 (Kvβ2.2) (AKR6A5-002,-202). This nomenclature is expandable and it enables multiple protein isoforms to be assigned to their respective transcripts when they arise from the same AKR gene or for a single protein isoform to be assigned to multiple transcripts when the transcripts encode the same AKR protein.

  10. Preliminary Results of the NASA Beacon Receiver for Alphasat Aldo Paraboni TDP5 Propagation Experiment

    NASA Technical Reports Server (NTRS)

    Nessel, James; Morse, Jacquelynne; Zemba, Michael; Riva, Carlo; Luini, Lorenzo

    2014-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 GHz band. NASA GRC has developed and installed a K/Q-band (20/40 GHz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 GHz signals broadcast from the Alphasat Aldo Paraboni TDP#5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we describe the design and preliminary performance of the NASA propagation terminal, which has been installed and operating in Milan since May 2014. The receiver is based upon a validated Fast Fourier Transform (FFT) I/Q digital design approach utilized in other operational NASA propagation terminals, but has been modified to employ power measurement via a frequency estimation technique and to coherently track and measure the amplitude of the 20/40 GHz beacon signals. The system consists of a 1.2-m K-band and a 0.6-m Qband Cassegrain reflector employing synchronous open-loop tracking to track the inclined orbit of the Alphasat satellite. An 8 Hz sampling rate is implemented to characterize scintillation effects, with a 1-Hz measurement bandwidth dynamic range of 45 dB. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  11. Human Aldo-Keto Reductases and the Metabolic Activation of Polycyclic Aromatic Hydrocarbons

    PubMed Central

    2015-01-01

    Aldo-keto reductases (AKRs) are promiscuous NAD(P)(H) dependent oxidoreductases implicated in the metabolic activation of polycyclic aromatic hydrocarbons (PAH). These enzymes catalyze the oxidation of non-K-region trans-dihydrodiols to the corresponding o-quinones with the concomitant production of reactive oxygen species (ROS). The PAH o-quinones are Michael acceptors and can form adducts but are also redox-active and enter into futile redox cycles to amplify ROS formation. Evidence exists to support this metabolic pathway in humans. The human recombinant AKR1A1 and AKR1C1–AKR1C4 enzymes all catalyze the oxidation of PAH trans-dihydrodiols to PAH o-quinones. Many human AKRs also catalyze the NADPH-dependent reduction of the o-quinone products to air-sensitive catechols, exacerbating ROS formation. Moreover, this pathway of PAH activation occurs in a panel of human lung cell lines, resulting in the production of ROS and oxidative DNA damage in the form of 8-oxo-2′-deoxyguanosine. Using stable-isotope dilution liquid chromatography tandem mass spectrometry, this pathway of benzo[a]pyrene (B[a]P) metabolism was found to contribute equally with the diol-epoxide pathway to the activation of this human carcinogen in human lung cells. Evaluation of the mutagenicity of anti-B[a]P-diol epoxide with B[a]P-7,8-dione on p53 showed that the o-quinone produced by AKRs was the more potent mutagen, provided that it was permitted to redox cycle, and that the mutations observed were G to T transversions, reminiscent of those observed in human lung cancer. It is concluded that there is sufficient evidence to support the role of human AKRs in the metabolic activation of PAH in human lung cell lines and that they may contribute to the causation of human lung cancer. PMID:25279998

  12. 9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant.

    PubMed

    Matsunaga, Toshiyuki; Haga, Mariko; Watanabe, Gou; Shinoda, Yuhki; Endo, Satoshi; Kajiwara, Yu; Tanaka, Hiroyuki; Inagaki, Naoki; El-Kabbani, Ossama; Hara, Akira

    2012-02-01

    9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, induces apoptosis via the generation of reactive oxygen species (ROS) because of 9,10-PQ redox cycling. We have found that intratracheal infusion of 9,10-PQ facilitates the secretion of surfactant into rat alveolus. In the cultured rat lung, treatment with 9,10-PQ results in an increase in a lower-density surfactant by ROS generation through redox cycling of the quinone. The surfactant contains aldo-keto reductase (AKR) 1C15, which reduces 9,10-PQ and the enzyme level in the surfactant increases on treatment with 9,10-PQ suggesting an involvement of AKR1C15 in the redox cycling of the quinone. In six human cell types (A549, MKN45, Caco2, Hela, Molt4 and U937) only type II epithelial A549 cells secrete three human AKR1C subfamily members (AKR1C1, AKR1C2 and AKR1C3) with the surfactant into the medium; this secretion is highly increased by 9,10-PQ treatment. Using in vitro enzyme inhibition analysis, we have identified AKR1C3 as the most abundantly secreted AKR1C member. The AKR1C enzymes in the medium efficiently reduce 9,10-PQ and initiate its redox cycling accompanied by ROS production. The exposure of A549 cells to 9,10-PQ provokes viability loss, which is significantly protected by the addition of the AKR1C3 inhibitor and antioxidant enzyme and by the removal of the surfactants from the culture medium. Thus, the AKR1C enzymes secreted in pulmonary surfactants probably participate in the toxic mechanism triggered by 9,10-PQ. PMID:22281686

  13. Performance of the NASA Beacon Receiver for the Alphasat Aldo Paraboni TDP5 Propagation Experiment

    NASA Technical Reports Server (NTRS)

    Nessel, James; Morse, Jacquelynne; Zemba, Michael; Riva, Carlo; Luini, Lorenzo

    2015-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 gigahertz band. NASA GRC has developed and installed a K/Q-band (20/40 gigahertz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 gigahertz signals broadcast from the Alphasat Aldo Paraboni Technology Demonstration Payload (TDP) no. 5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we describe the design and preliminary performance of the NASA propagation terminal, which has been installed and operating in Milan since June 2014. The receiver is based upon a validated Fast Fourier Transform (FFT) I/Q digital design approach utilized in other operational NASA propagation terminals, but has been modified to employ power measurement via a frequency estimation technique and to coherently track and measure the amplitude of the 20/40 gigahertz beacon signals. The system consists of a 1.2-meter K-band and a 0.6-meter Q-band Cassegrain reflector employing synchronous open-loop tracking to track the inclined orbit of the Alphasat satellite. An 8 hertz sampling rate is implemented to characterize scintillation effects, with a 1-hertz measurement bandwidth dynamic range of 45 decibels. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  14. Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism.

    PubMed

    Garavaglia, Patricia Andrea; Laverrière, Marc; Cannata, Joaquín J B; García, Gabriela Andrea

    2016-05-01

    Benznidazole (Bz), the drug used for treatment of Chagas' disease (caused by the protozoan Trypanosoma cruzi), is activated by a parasitic NADH-dependent type I nitroreductase (NTR I). However, several studies have shown that other enzymes are involved. The aim of this study was to evaluate whether the aldo-keto reductase from T. cruzi (TcAKR), a NADPH-dependent oxido-reductase previously described by our group, uses Bz as the substrate. We demonstrated that both recombinant and native TcAKR enzymes reduce Bz by using NADPH, but not NADH, as a cofactor. TcAKR-overexpressing epimastigotes showed higher NADPH-dependent Bz reductase activity and a 50% inhibitory concentration (IC50) value for Bz 1.8-fold higher than that of the controls, suggesting that TcAKR is involved in Bz detoxification instead of activation. To understand the role of TcAKR in Bz metabolism, we studied TcAKR expression and NADPH/NADH-dependent Bz reductase activities in two T. cruzi strains with differential susceptibility to Bz: CL Brener and Nicaragua. Taking into account the results obtained with TcAKR-overexpressing epimastigotes, we expected the more resistant strain, Nicaragua, to have higher TcAKR levels than CL Brener. However, the results were the opposite. CL Brener showed 2-fold higher TcAKR expression and 5.7-fold higher NADPH-Bz reduction than the Nicaragua strain. In addition, NADH-dependent Bz reductase activity, characteristic of NTR I, was also higher in CL Brener than in Nicaragua. We conclude that although TcAKR uses Bz as the substrate, TcAKR activity is not a determinant of Bz resistance in wild-type strains and may be overcome by other enzymes involved in Bz activation, such as NADPH- and NADH-dependent reductases. PMID:26856844

  15. Effect of cytochrome P450 and aldo-keto reductase inhibitors on progesterone inactivation in primary bovine hepatic cell cultures.

    PubMed

    Lemley, C O; Wilson, M E

    2010-10-01

    Progesterone is required for maintenance of pregnancy, and peripheral concentrations of progesterone are affected by both production and inactivation. Hepatic cytochrome P450 (EC 1.14.14.1) and aldo-keto reductase (EC 1.1.1.145-151) enzymes play a pivotal role in the first step of steroid inactivation, which involves the addition of hydroxyl groups to various sites of the cyclopentanoperhydrophenanthrene nucleus. The current objective was to discern the proportional involvement of hepatic progesterone inactivating enzymes on progesterone decay using specific enzyme inhibitors. Ticlopidine, diltiazem, curcumin, dicumarol, and naproxen were used because of their selective inhibition of cytochrome P450s, aldo-keto reductases, and glucuronosyltransferases. Liver biopsies were collected from 6 lactating Holstein dairy cows, and cells were dissociated using a nonperfusion technique. Confluent wells were preincubated for 4 h with enzyme inhibitor and then challenged with progesterone for 1 h. Cell viability was unaffected by inhibitor treatment and averaged 84±1%. In control wells, 50% of the progesterone had been inactivated after a 1-h challenge with 5 ng/mL of progesterone. Preincubation with curcumin, ticlopidine, or naproxen caused the greatest reduction in progesterone inactivation compared with controls and averaged 77, 39, or 37%, respectively. Hydroxylation of 4-nitrophenol to 4-nitrocatechol in intact cells was inhibited by approximately 65% after treatment with curcumin or ticlopidine. Glucuronidation of phenol red or 4-nitrocatechol in intact cells was inhibited by treatment with curcumin, dicumarol, or naproxen. In cytoplasmic preparations, aldo-keto reductase 1C activity was inhibited by curcumin, dicumarol, or naproxen treatment. Microsomal cytochrome P450 2C activity was inhibited by treatment with curcumin or ticlopidine, whereas cytochrome P450 3A activity was inhibited by treatment with curcumin or diltiazem. The contribution of cytochrome P450 2C and

  16. A potassium channel beta subunit related to the aldo-keto reductase superfamily is encoded by the Drosophila hyperkinetic locus.

    PubMed

    Chouinard, S W; Wilson, G F; Schlimgen, A K; Ganetzky, B

    1995-07-18

    Genetic and physiological studies of the Drosophila Hyperkinetic (Hk) mutant revealed defects in the function or regulation of K+ channels encoded by the Shaker (Sh) locus. The Hk polypeptide, determined from analysis of cDNA clones, is a homologue of mammalian K+ channel beta subunits (Kv beta). Coexpression of Hk with Sh in Xenopus oocytes increases current amplitudes and changes the voltage dependence and kinetics of activation and inactivation, consistent with predicted functions of Hk in vivo. Sequence alignments show that Hk, together with mammalian Kv beta, represents an additional branch of the aldo-keto reductase superfamily. These results are relevant to understanding the function and evolutionary origin of Kv beta.

  17. Crystallographic analysis of a novel aldo-keto reductase from Thermotoga maritima in complex with NADP⁺.

    PubMed

    Hou, Hai; Li, Ruiying; Wang, Xiaoyan; Yuan, Zhen; Liu, Xuemeng; Chen, Zhenmin; Xu, Xiaoling

    2015-07-01

    Aldo-keto reductases (AKRs) are a superfamily of NAD(P)H-dependent oxidoreductases that catalyse the asymmetric reduction of aldehydes and ketones to chiral alcohols in various organisms. The novel aldo-keto reductase Tm1743 from Thermotoga maritima was identified to have a broad substrate specificity and high thermostability, serving as an important enzyme in biocatalysis and fine-chemical synthesis. In this study, Tm1743 was overexpressed in Escherichia coli BL21(DE3) cells with an N-terminal His6 tag and was purified by Ni(2+)-chelating affinity and size-exclusion chromatography. Purified recombinant enzyme was incubated with its cofactor NADP(+) and its substrate ethyl 2-oxo-4-phenylbutyrate (EOPB) for crystallization. Two X-ray diffraction data sets were collected at 2.0 and 1.7 Å resolution from dodecahedral crystals grown from samples containing Tm1743-NADP(+)-EOPB and Tm1743-NADP(+), respectively. Both crystals belonged to space group P3121, with similar unit-cell parameters. However, in the refined structure model only NADP(+) was observed in the active site of the full-length Tm1743 enzyme. Degradation of the N-terminal vector-derived amino acids during crystallization was confirmed by Western blot and mass-spectrometric analyses.

  18. Substrate specificity and catalytic efficiency of aldo-keto reductases with phospholipid aldehydes.

    PubMed

    Spite, Matthew; Baba, Shahid P; Ahmed, Yonis; Barski, Oleg A; Nijhawan, Kanchan; Petrash, J Mark; Bhatnagar, Aruni; Srivastava, Sanjay

    2007-07-01

    Phospholipid oxidation generates several bioactive aldehydes that remain esterified to the glycerol backbone ('core' aldehydes). These aldehydes induce endothelial cells to produce monocyte chemotactic factors and enhance monocyte-endothelium adhesion. They also serve as ligands of scavenger receptors for the uptake of oxidized lipoproteins or apoptotic cells. The biochemical pathways involved in phospholipid aldehyde metabolism, however, remain largely unknown. In the present study, we have examined the efficacy of the three mammalian AKR (aldo-keto reductase) families in catalysing the reduction of phospholipid aldehydes. The model phospholipid aldehyde POVPC [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine] was efficiently reduced by members of the AKR1, but not by the AKR6 or the ARK7 family. In the AKR1 family, POVPC reductase activity was limited to AKR1A and B. No significant activity was observed with AKR1C enzymes. Among the active proteins, human AR (aldose reductase) (AKR1B1) showed the highest catalytic activity. The catalytic efficiency of human small intestinal AR (AKR1B10) was comparable with the murine AKR1B proteins 1B3 and 1B8. Among the murine proteins AKR1A4 and AKR1B7 showed appreciably lower catalytic activity as compared with 1B3 and 1B8. The human AKRs, 1B1 and 1B10, and the murine proteins, 1B3 and 1B8, also reduced C-7 and C-9 sn-2 aldehydes as well as POVPE [1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphoethanolamine]. AKR1A4, B1, B7 and B8 catalysed the reduction of aldehydes generated in oxidized C(16:0-20:4) phosphatidylcholine with acyl, plasmenyl or alkyl linkage at the sn-1 position or C(16:0-20:4) phosphatidylglycerol or phosphatidic acid. AKR1B1 displayed the highest activity with phosphatidic acids; AKR1A4 was more efficient with long-chain aldehydes such as 5-hydroxy-8-oxo-6-octenoyl derivatives, whereas AKR1B8 preferred phosphatidylglycerol. These results suggest that proteins of the AKR1A and B families are

  19. Wide area scanning system and carbon microbeams at the external microbeam facility of the INFN LABEC laboratory in Florence

    NASA Astrophysics Data System (ADS)

    Giuntini, L.; Massi, M.; Calusi, S.; Castelli, L.; Carraresi, L.; Fedi, M. E.; Gelli, N.; Liccioli, L.; Mandò, P. A.; Mazzinghi, A.; Palla, L.; Romano, F. P.; Ruberto, C.; Taccetti, F.

    2015-04-01

    Recently, developments have been made to the external scanning microbeam of INFN-LABEC laboratory in Florence. A new system for mechanical sample scanning was implemented. This system allows us to acquire large maps (up to 20 × 20 cm2), of great interest in the Cultural Heritage field. In parallel, the possibility of using carbon microbeams for experiments, such as, for example, ion beam modification of materials and MeV Secondary Ion Mass Spectrometry, has been investigated. As a test application, Particle Induced X-ray Emission with carbon microbeams has been performed on a lapis lazuli stone. First results for both wide area imaging and external carbon microbeams are briefly reported.

  20. Status of the SPES-charge breeder (SPES-CB) and its beam line at INFN-LNL

    NASA Astrophysics Data System (ADS)

    Galatá, Àlessio; Comunian, M.; Bellan, L.; Maggiore, M.; Patti, G.; Roncolato, C.; Bisoffi, G.; Russo, A. D.; Calabretta, L.; Angot, J.; Lamy, T.

    2016-06-01

    The Selective Production of Exotic Species (SPES) facility is under construction at INFN-LNL: aim of this project is the production, ionization and post-acceleration of radioactive ions to perform forefront research in nuclear physics. Radioactive species will be produced by fissions induced by a proton beam impinging on an UCx target: the proton beam will be delivered by a room temperature cyclotron (built by the Best Company) with a maximum energy of 40 MeV and 0.25 mA of maximum current. The radioactive species produced in the Target-Ion-Source system, extracted as a 1+ beam, cooled in a RFQ-cooler and purified from the isobars contaminants through a High Resolution Mass Spectrometer (HRMS). In order to allow post acceleration with the superconducting linac ALPI at INFN-LNL (up to 10 MeV/A for A/q = 7), an ECR-based charge breeding technique (ECR-CB) was chosen: in particular the SPES-CB was developed by the LPSC Grenoble on the basis of the Phoenix booster. The SPES-CB will be equipped with a complete test bench, totally integrated with the SPES beam line: in particular, in order to avoid beam contaminations induced by the impurities present inside the SPES-CB, and to have high transmission for a beam of very low intensity, special attention was paid not only to the transport efficiency but also to the resolution of the spectrometer downstream the charge breeder, with the design of a Medium Resolution Mass Spectrometer (MRMS). In the following paper the technical aspects connected with SPES-CB, its beam line and the transport of highly charged radioactive ions will be described.

  1. Pyrithione-based ruthenium complexes as inhibitors of aldo-keto reductase 1C enzymes and anticancer agents.

    PubMed

    Kljun, Jakob; Anko, Maja; Traven, Katja; Sinreih, Maša; Pavlič, Renata; Peršič, Špela; Ude, Žiga; Codina, Elisa Esteve; Stojan, Jure; Lanišnik Rižner, Tea; Turel, Iztok

    2016-08-01

    Four ruthenium complexes of clinically used zinc ionophore pyrithione and its oxygen analog 2-hydroxypyridine N-oxide were prepared and evaluated as inhibitors of enzymes of the aldo-keto reductase subfamily 1C (AKR1C). A kinetic study assisted with docking simulations showed a mixed type of inhibition consisting of a fast reversible and a slow irreversible step in the case of both organometallic compounds 1A and 1B. Both compounds also showed a remarkable selectivity towards AKR1C1 and AKR1C3 which are targets for breast cancer drug design. The organoruthenium complex of ligand pyrithione as well as pyrithione itself also displayed toxicity on the hormone-dependent MCF-7 breast cancer cell line with EC50 values in the low micromolar range. PMID:27357845

  2. The new ECR charge breeder for the Selective Production of Exotic Species project at INFN--Laboratori Nazionali di Legnaro.

    PubMed

    Galatà, A; Patti, G; Roncolato, C; Angot, J; Lamy, T

    2016-02-01

    The Selective Production of Exotic Species (SPES) project is an ISOL facility under construction at Istituto Nazionale di Fisica Nucleare-Laboratori Nationali di Legnaro (INFN-LNL). 1+ radioactive ions, produced and extracted from the target-ion-source system, will be charge bred to high charge states by an ECR charge breeder (SPES-CB): the project will adopt an upgraded version of the PHOENIX charge breeder, developed since about twenty years by the Laboratoire de Physique Subatomique et de Cosmologie (LPSC). The collaboration between LNL and LPSC started in 2010 with charge breeding experiments performed on the LPSC test bench and led, in June 2014, to the signature of a Research Collaboration Agreement for the delivery of a complete charge breeder and ancillaries, satisfying the SPES requirements. Important technological aspects were tackled during the construction phase, as, for example, beam purity issues, electrodes alignment, and vacuum sealing. This phase was completed in spring 2015, after which the qualification tests were carried out at LPSC on the 1+/q+ test stand. This paper describes the characteristics of the SPES-CB, with particular emphasis on the results obtained during the qualification tests: charge breeding of Ar, Xe, Rb, and Cs satisfied the SPES requirements for different intensities of the injected 1+ beam, showing very good performances, some of which are "best ever" for this device. PMID:26932056

  3. First Experiences with CMS Data Storage on the GEMSS System at the INFN-CNAF Tier-1

    NASA Astrophysics Data System (ADS)

    Andreotti, D.; Bonacorsi, D.; Cavalli, A.; Pra, S. Dal; Dell'Agnello, L.; Forti, Alberto; Grandi, C.; Gregori, D.; Gioi, L. Li; Martelli, B.; Prosperini, A.; Ricci, P. P.; Ronchieri, Elisabetta; Sapunenko, V.; Sartirana, A.; Vagnoni, V.; Zappi, Riccardo

    A brand new Mass Storage System solution called "Grid-Enabled Mass Storage System" (GEMSS) -based on the Storage Resource Manager (StoRM) developed by INFN, on the General Parallel File System by IBM and on the Tivoli Storage Manager by IBM -has been tested and deployed at the INFNCNAF Tier-1 Computing Centre in Italy. After a successful stress test phase, the solution is now being used in production for the data custodiality of the CMS experiment at CNAF. All data previously recorded on the CASTOR system have been transferred to GEMSS. As final validation of the GEMSS system, some of the computing tests done in the context of the WLCG "Scale Test for the Experiment Program" (STEP'09) challenge were repeated in September-October 2009 and compared with the results previously obtained with CASTOR in June 2009. In this paper, the GEMSS system basics, the stress test activity and the deployment phase -as well as the reliability and performance of the system -are overviewed. The experiences in the use of GEMSS at CNAF in preparing for the first months of data taking of the CMS experiment at the Large Hadron Collider are also presented.

  4. ALDO: A radiation-tolerant, low-noise, adjustable low drop-out linear regulator in 0.35 μm CMOS technology

    NASA Astrophysics Data System (ADS)

    Carniti, P.; Cassina, L.; Gotti, C.; Maino, M.; Pessina, G.

    2016-07-01

    In this work we present ALDO, an adjustable low drop-out linear regulator designed in AMS 0.35 μm CMOS technology. It is specifically tailored for use in the upgraded LHCb RICH detector in order to improve the power supply noise for the front end readout chip (CLARO). ALDO is designed with radiation-tolerant solutions such as an all-MOS band-gap voltage reference and layout techniques aiming to make it able to operate in harsh environments like High Energy Physics accelerators. It is capable of driving up to 200 mA while keeping an adequate power supply filtering capability in a very wide frequency range from 10 Hz up to 100 MHz. This property allows us to suppress the noise and high frequency spikes that could be generated by a DC/DC regulator, for example. ALDO also shows a very low noise of 11.6 μV RMS in the same frequency range. Its output is protected with over-current and short detection circuits for a safe integration in tightly packed environments. Design solutions and measurements of the first prototype are presented.

  5. A pathogenesis related-10 protein CaARP functions as aldo/keto reductase to scavenge cytotoxic aldehydes.

    PubMed

    Jain, Deepti; Khandal, Hitaishi; Khurana, Jitendra Paul; Chattopadhyay, Debasis

    2016-01-01

    Pathogenesis related-10 (PR-10) proteins are present as multigene family in most of the higher plants. The role of PR-10 proteins in plant is poorly understood. A sequence analysis revealed that a large number of PR-10 proteins possess conserved motifs found in aldo/keto reductases (AKRs) of yeast and fungi. We took three PR-10 proteins, CaARP from chickpea, ABR17 from pea and the major pollen allergen Bet v1 from silver birch as examples and showed that these purified recombinant proteins possessed AKR activity using various cytotoxic aldehydes including methylglyoxal and malondialdehyde as substrates and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) as co-factor. Essential amino acids for this catalytic activity were identified by substitution with other amino acids. CaARP was able to discriminate between the reduced and oxidized forms of NADP independently of its catalytic activity and underwent structural change upon binding with NADPH. CaARP protein was preferentially localized in cytosol. When expressed in bacteria, yeast or plant, catalytically active variants of CaARP conferred tolerance to salinity, oxidative stress or cytotoxic aldehydes. CaARP-expressing plants showed lower lipid peroxidation product content in presence or absence of stress suggesting that the protein functions as a scavenger of cytotoxic aldehydes produced by metabolism and lipid peroxidation. Our result proposes a new biochemical property of a PR-10 protein.

  6. A pathogenesis related-10 protein CaARP functions as aldo/keto reductase to scavenge cytotoxic aldehydes.

    PubMed

    Jain, Deepti; Khandal, Hitaishi; Khurana, Jitendra Paul; Chattopadhyay, Debasis

    2016-01-01

    Pathogenesis related-10 (PR-10) proteins are present as multigene family in most of the higher plants. The role of PR-10 proteins in plant is poorly understood. A sequence analysis revealed that a large number of PR-10 proteins possess conserved motifs found in aldo/keto reductases (AKRs) of yeast and fungi. We took three PR-10 proteins, CaARP from chickpea, ABR17 from pea and the major pollen allergen Bet v1 from silver birch as examples and showed that these purified recombinant proteins possessed AKR activity using various cytotoxic aldehydes including methylglyoxal and malondialdehyde as substrates and the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) as co-factor. Essential amino acids for this catalytic activity were identified by substitution with other amino acids. CaARP was able to discriminate between the reduced and oxidized forms of NADP independently of its catalytic activity and underwent structural change upon binding with NADPH. CaARP protein was preferentially localized in cytosol. When expressed in bacteria, yeast or plant, catalytically active variants of CaARP conferred tolerance to salinity, oxidative stress or cytotoxic aldehydes. CaARP-expressing plants showed lower lipid peroxidation product content in presence or absence of stress suggesting that the protein functions as a scavenger of cytotoxic aldehydes produced by metabolism and lipid peroxidation. Our result proposes a new biochemical property of a PR-10 protein. PMID:26577640

  7. Gene expression and promoter analysis of a novel tomato aldo-keto reductase in response to environmental stresses.

    PubMed

    Suekawa, Marina; Fujikawa, Yukichi; Inada, Shuhei; Murano, Asako; Esaka, Muneharu

    2016-08-01

    The functional role of an uncharacterized tomato (Solanum lycopersicum) aldo-keto reductase 4B, denoted as SlAKR4B, was investigated. The gene expression of tomato SlAKR4B was detected at a high level in the senescent leaves and the ripening fruits of tomato. Although d-galacturonic acid reductase activities tended to be higher in tomato SlAKR4B-overexpressing transgenic tobacco BY-2 cell lines than those in control cell lines, SlAKR4B gene expression was not well correlated with l-ascorbic acid content among the cell lines. The analysis of the transgenic cell lines showed that tomato SlAKR4B has enzyme activities toward d-galacturonic acid as well as glyceraldehyde and glyoxal, suggesting that the SlAKR4B gene encodes a functional enzyme in tomato. Gene expression of SlAKR4B was induced by NaCl, H2O2, and plant hormones such as salicylic acid and jasmonic acid, suggesting that SlAKR4B is involved in the stress response. The transient expression assay using protoplasts showed the promoter activity of the SlAKR4B gene was as high as that of the cauliflower mosaic virus 35S promoter. Also, the promoter region of the SlAKR4B gene was suggested to contain cis-element(s) for abiotic stress-inducible expression. PMID:27337067

  8. Aldo Leopold's land health from a resilience point of view: self-renewal capacity of social-ecological systems.

    PubMed

    Berkes, Fikret; Doubleday, Nancy C; Cumming, Graeme S

    2012-09-01

    Health approaches to ecology have a strong basis in Aldo Leopold's thinking, and contemporary ecohealth in turn has a strong philosophical basis in Leopold. To commemorate the 125th anniversary of Leopold's birth (1887-1948), we revisit his ideas, specifically the notions of stewardship (land ethic), productive use of ecosystems (land), and ecosystem renewal. We focus on Leopold's perspective on the self-renewal capacity of the land, as understood in terms of integrity and land health, from the contemporary perspective of resilience theory and ecological theory more generally. Using a broad range of literature, we explore insights and implications of Leopold's work for today's human-environment relationships (integrated social-ecological systems), concerns for biodiversity, the development of agency with respect to stewardship, and key challenges of his time and of ours. Leopold's seminal concept of land health can be seen as a triangulation of productive use, self-renewal, and stewardship, and it can be reinterpreted through the resilience lens as the health of social-ecological systems. In contemporary language, this involves the maintenance of biodiversity and ecosystem services, and the ability to exercise agency both for conservation and for environmental justice.

  9. Design and implementation of a reliable and cost-effective cloud computing infrastructure: the INFN Napoli experience

    NASA Astrophysics Data System (ADS)

    Capone, V.; Esposito, R.; Pardi, S.; Taurino, F.; Tortone, G.

    2012-12-01

    Over the last few years we have seen an increasing number of services and applications needed to manage and maintain cloud computing facilities. This is particularly true for computing in high energy physics, which often requires complex configurations and distributed infrastructures. In this scenario a cost effective rationalization and consolidation strategy is the key to success in terms of scalability and reliability. In this work we describe an IaaS (Infrastructure as a Service) cloud computing system, with high availability and redundancy features, which is currently in production at INFN-Naples and ATLAS Tier-2 data centre. The main goal we intended to achieve was a simplified method to manage our computing resources and deliver reliable user services, reusing existing hardware without incurring heavy costs. A combined usage of virtualization and clustering technologies allowed us to consolidate our services on a small number of physical machines, reducing electric power costs. As a result of our efforts we developed a complete solution for data and computing centres that can be easily replicated using commodity hardware. Our architecture consists of 2 main subsystems: a clustered storage solution, built on top of disk servers running GlusterFS file system, and a virtual machines execution environment. GlusterFS is a network file system able to perform parallel writes on multiple disk servers, providing this way live replication of data. High availability is also achieved via a network configuration using redundant switches and multiple paths between hypervisor hosts and disk servers. We also developed a set of management scripts to easily perform basic system administration tasks such as automatic deployment of new virtual machines, adaptive scheduling of virtual machines on hypervisor hosts, live migration and automated restart in case of hypervisor failures.

  10. Aldo-keto Reductase 1B15 (AKR1B15): a mitochondrial human aldo-keto reductase with activity toward steroids and 3-keto-acyl-CoA conjugates.

    PubMed

    Weber, Susanne; Salabei, Joshua K; Möller, Gabriele; Kremmer, Elisabeth; Bhatnagar, Aruni; Adamski, Jerzy; Barski, Oleg A

    2015-03-01

    Aldo-keto reductases (AKRs) comprise a superfamily of proteins involved in the reduction and oxidation of biogenic and xenobiotic carbonyls. In humans, at least 15 AKR superfamily members have been identified so far. One of these is a newly identified gene locus, AKR1B15, which clusters on chromosome 7 with the other human AKR1B subfamily members (i.e. AKR1B1 and AKR1B10). We show that alternative splicing of the AKR1B15 gene transcript gives rise to two protein isoforms with different N termini: AKR1B15.1 is a 316-amino acid protein with 91% amino acid identity to AKR1B10; AKR1B15.2 has a prolonged N terminus and consists of 344 amino acid residues. The two gene products differ in their expression level, subcellular localization, and activity. In contrast with other AKR enzymes, which are mostly cytosolic, AKR1B15.1 co-localizes with the mitochondria. Kinetic studies show that AKR1B15.1 is predominantly a reductive enzyme that catalyzes the reduction of androgens and estrogens with high positional selectivity (17β-hydroxysteroid dehydrogenase activity) as well as 3-keto-acyl-CoA conjugates and exhibits strong cofactor selectivity toward NADP(H). In accordance with its substrate spectrum, the enzyme is expressed at the highest levels in steroid-sensitive tissues, namely placenta, testis, and adipose tissue. Placental and adipose expression could be reproduced in the BeWo and SGBS cell lines, respectively. In contrast, AKR1B15.2 localizes to the cytosol and displays no enzymatic activity with the substrates tested. Collectively, these results demonstrate the existence of a novel catalytically active AKR, which is associated with mitochondria and expressed mainly in steroid-sensitive tissues.

  11. Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

    PubMed Central

    Lambert-Langlais, Sarah; Volat, Fanny; Manin, Michèle; Coudoré, François; Val, Pierre; Sahut-Barnola, Isabelle; Ragazzon, Bruno; Louiset, Estelle; Delarue, Catherine; Lefebvre, Hervé; Urade, Yoshihiro; Martinez, Antoine

    2009-01-01

    Prostaglandin F2α (PGF2α), represses ovarian steroidogenesis and initiates parturition in mammals but its impact on adrenal gland is unknown. Prostaglandins biosynthesis depends on the sequential action of upstream cyclooxygenases (COX) and terminal synthases but no PGF2α synthases (PGFS) were functionally identified in mammalian cells. In vitro, the most efficient mammalian PGFS belong to aldo-keto reductase 1B (AKR1B) family. The adrenal gland is a major site of AKR1B expression in both human (AKR1B1) and mouse (AKR1B3, AKR1B7). Thus, we examined the PGF2α biosynthetic pathway and its functional impact on both cortical and medullary zones. Both compartments produced PGF2α but expressed different biosynthetic isozymes. In chromaffin cells, PGF2α secretion appeared constitutive and correlated to continuous expression of COX1 and AKR1B3. In steroidogenic cells, PGF2α secretion was stimulated by adrenocorticotropic hormone (ACTH) and correlated to ACTH-responsiveness of both COX2 and AKR1B7/B1. The pivotal role of AKR1B7 in ACTH-induced PGF2α release and functional coupling with COX2 was demonstrated using over- and down-expression in cell lines. PGF2α receptor was only detected in chromaffin cells, making medulla the primary target of PGF2α action. By comparing PGF2α-responsiveness of isolated cells and whole adrenal cultures, we demonstrated that PGF2α repressed glucocorticoid secretion by an indirect mechanism involving a decrease in catecholamine release which in turn decreased adrenal steroidogenesis. PGF2α may be regarded as a negative autocrine/paracrine regulator within a novel intra-adrenal feedback loop. The coordinated cell-specific regulation of COX2 and AKR1B7 ensures the generation of this stress-induced corticostatic signal. PMID:19809495

  12. Aldo-keto reductase 1b7, a novel marker for renin cells, is regulated by cyclic AMP signaling

    PubMed Central

    Lin, Eugene E.; Pentz, Ellen S.; Sequeira-Lopez, Maria Luisa S.

    2015-01-01

    We previously identified aldo-keto reductase 1b7 (AKR1B7) as a marker for juxtaglomerular renin cells in the adult mouse kidney. However, the distribution of renin cells varies dynamically, and it was unknown whether AKR1B7 maintains coexpression with renin in response to different developmental, physiological, and pathological situations, and furthermore, whether similar factor(s) simultaneously regulate both proteins. We show here that throughout kidney development, AKR1B7 expression—together with renin—is progressively restricted in the kidney arteries toward the glomerulus. Subsequently, when formerly renin-expressing cells reacquire renin expression, AKR1B7 is reexpressed as well. This pattern of coexpression persists in extreme pathological situations, such as deletion of the genes for aldosterone synthase or Dicer. However, the two proteins do not colocalize within the same organelles: renin is found in the secretory granules, whereas AKR1B7 localizes to the endoplasmic reticulum. Interestingly, upon deletion of the renin gene, AKR1B7 expression is maintained in a pattern mimicking the embryonic expression of renin, while ablation of renin cells resulted in complete abolition of AKR1B7 expression. Finally, we demonstrate that AKR1B7 transcription is controlled by cAMP. Cultured cells of the renin lineage reacquire the ability to express both renin and AKR1B7 upon elevation of intracellular cAMP. In vivo, deleting elements of the cAMP-response pathway (CBP/P300) results in a stark decrease in AKR1B7- and renin-positive cells. In summary, AKR1B7 is expressed within the renin cell throughout development and perturbations to homeostasis, and AKR1B7 is regulated by cAMP levels within the renin cell. PMID:26180185

  13. Expression of Aldo-Keto Reductase Family 1 Member B10 in the Early Stages of Human Hepatocarcinogenesis

    PubMed Central

    Tsuzura, Hironori; Genda, Takuya; Sato, Shunsuke; Murata, Ayato; Kanemitsu, Yoshio; Narita, Yutaka; Ishikawa, Sachiko; Kikuchi, Tetsu; Mori, Masashi; Hirano, Katsuharu; Iijima, Katsuyori; Wada, Ryo; Ichida, Takafumi

    2014-01-01

    Aldo-keto reductase family 1, member B10 (AKR1B10), a cancer-related oxidoreductase, is expressed in well-differentiated hepatocellular carcinomas (HCCs). However, AKR1B10 levels are minimal in normal liver tissues (NLs), similar to the 70-kilodalton heat shock protein (HSP70) and glypican-3. Moreover, the role of AKR1B10 in chronic hepatitis or cirrhosis, which are considered preneoplastic conditions for HCC, has not been fully elucidated. The aim of this study was to evaluate the expression of AKR1B10, HSP70, and glypican-3 in 61 HCC tissue samples compared to corresponding non-tumorous liver tissues (NTs), comprising 42 chronic hepatitis and 19 cirrhosis cases to clarify the significance of molecular changes at the preneoplastic stages of HCC. Immunohistochemical analysis demonstrated that the median expression levels of AKR1B10 were higher in HCCs than in NTs (p < 0.001) and higher in NTs than NLs (p < 0.001) with 54.8%, 2.1%, and 0.3% expression in HCCs, NTs, and NLs, respectively. HSP70 and glypican-3 were expressed in HCCs, but minimally in NTs and NLs with no significant difference between expression in NTs and NLs. Furthermore, a multivariate analysis identified an association between hepatic steatosis and AKR1B10 expression in NTs (p = 0.020). Of the three protein expressed in well-differentiated HCCs, only AKR1B10 was upregulated in preneoplastic conditions, and a steatosis-related factor might influence its expression. PMID:24747592

  14. MoonLIGHT, a Lunar Laser Ranging Retroreflector Array for the 21st Century, and the ASI-INFN Etrusco-2 project

    NASA Astrophysics Data System (ADS)

    Delle Monache, Giovanni O.; Dell'Agnello, S.; Currie, D.; Martini, M.; Vittori, R.; Cantone, C.; Boni, A.; Berardi, S.; Patrizi, G.; Maiello, M.; Tibuzzi, M.; Garattini, M.; Lops, C.; Ciocci, E.; Graziosi, C.; Bianco, G.; Intaglietta, N.

    2012-05-01

    Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays supplied almost all significant tests of General Relativity and significant information on the composition and origin of the moon. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single CCR unaffected by librations. In particular, INFN-LNF built and is operating a new experimental apparatus (SCF) and created a new industry-standard test procedure (SCF-Test) to characterize the thermal behavior and the optical performance of CCRs in simulated space conditions. Our key experimental innovation is the concurrent measurement and modeling of the optical FFDP and the temperature distribution of retroreflector payloads under thermal conditions produced with a close-match solar simulator. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR. Results of the SCF-Test of our CCR payload will be presented. Negotiations are underway to propose our payload and SCF-Test services for precision gravity and lunar science measurements with next robotic lunar landing missions. We will describe the addition of the CCR optical Wavefront Fizeau Interferogram (WFI) concurrently to FFDP/temperature measurements in the framework of an ASI-INFN project, ETRUSCO-2. The main goals of the latter are: development of a standard GNSS laser Retroreflector Array; a second SCF; SCF-Test of Galileo, GPS and other ‘as-built’ GNSS retroreflector payloads. Results on analysis of Apollo LLR data and search of new gravitational physics with LLR, Mercury Radar Ranging, SLR of LAGEOS (Laser GEOdynamics Satellite) will

  15. Identification of a role for a mouse sperm surface aldo-keto reductase (AKR1B7) and its human analogue in the detoxification of the reactive aldehyde, acrolein.

    PubMed

    Jagoe, W N; Howe, K; O'Brien, S C; Carroll, J

    2013-10-01

    Mouse vas deferens protein (AKR1B7), a member of the aldo-keto reductase family, was purified to homogeneity. Antibodies raised to AKR1B7 revealed an aldo-keto reductase on the human sperm surface, while confocal microscopy experiments demonstrated that this enzyme covered the entire human sperm surface and was concentrated on the mid-piece. Further functional characterisation of a recombinant form of AKR1B7 showed that the likely role of AKR1B7 is the reduction of the reactive aldehyde, acrolein, a by-product of spermine catabolism in the reproductive tract. A similar acrolein detoxification activity was displayed by human sperm membrane extracts but was not present in seminal plasma. These results indicate that human sperm possess an aldo-keto reductase on their membrane surface and are thus enzymatically protected against reactive aldehyde species both in the male and female reproductive tract.

  16. The set-up for forward scattered particle detection at the external microbeam facility of the INFN-LABEC laboratory in Florence

    NASA Astrophysics Data System (ADS)

    Giuntini, L.; Massi, M.; Calusi, S.; Gelli, N.; Castelli, L.; Carraresi, L.; Czelusniak, C.; Fedi, M. E.; Gueli, A. M.; Liccioli, L.; Mandò, P. A.; Mazzinghi, A.; Palla, L.; Ruberto, C.; Taccetti, F.

    2015-04-01

    In the last few years some new implementations and upgrades have been made to the external scanning microbeam of INFN-LABEC laboratory in Florence, enriching the existing PIXE, PIGE, BS, IBIL set-up with complementary techniques, when possible allowing for simultaneous multi-technique analyses. We developed a system, compatible with the existing set-up, for the out-of-vacuum detection of the forward scattered particles. This system makes feasible the external-STIM (Scanning Transmission Ion Microscopy) and external-FS (Forward Scattering), now both available at our beamline. Test measurements are shortly presented.

  17. Expression, purification, crystallization and preliminary X-ray analysis of perakine reductase, a new member of the aldo-keto reductase enzyme superfamily from higher plants

    SciTech Connect

    Rosenthal, Cindy; Mueller, Uwe; Panjikar, Santosh; Sun, Lianli; Ruppert, Martin; Zhao, Yu; Stöckigt, Joachim

    2006-12-01

    Perakine reductase, a novel member of the aldo-keto reductase enzyme superfamily of higher plants, is involved in the biosynthesis of monoterpenoid indole alkaloids in the Indian medicinal plant Rauvolfia serpentina. The enzyme has been crystallized in C-centered orthorhombic space group and diffracts to 2.0 Å resolution. Perakine reductase (PR) is a novel member of the aldo-keto reductase enzyme superfamily from higher plants. PR from the plant Rauvolfia serpentina is involved in the biosynthesis of monoterpenoid indole alkaloids by performing NADPH-dependent reduction of perakine, yielding raucaffrinoline. However, PR can also reduce cinnamic aldehyde and some of its derivatives. After heterologous expression of a triple mutant of PR in Escherichia coli, crystals of the purified and methylated enzyme were obtained by the hanging-drop vapour-diffusion technique at 293 K with 100 mM sodium citrate pH 5.6 and 27% PEG 4000 as precipitant. Crystals belong to space group C222{sub 1} and diffract to 2.0 Å, with unit-cell parameters a = 58.9, b = 93.0, c = 143.4 Å.

  18. Rat NAD+-dependent 3alpha-hydroxysteroid dehydrogenase (AKR1C17): a member of the aldo-keto reductase family highly expressed in kidney cytosol.

    PubMed

    Sanai, Masaharu; Endo, Satoshi; Matsunaga, Toshiyuki; Ishikura, Shuhei; Tajima, Kazuo; El-Kabbani, Ossama; Hara, Akira

    2007-08-01

    Mammalian 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs) have been divided into two types: Cytosolic NADP(H)-dependent 3alpha-HSDs belonging to the aldo-keto reductase family, and mitochondrial and microsomal NAD(+)-dependent 3alpha-HSDs belonging to the short-chain dehydrogenase/reductase family. In this study, we characterized a rat aldo-keto reductase (AKR1C17), whose functions are unknown. The recombinant AKR1C17 efficiently oxidized 3alpha-hydroxysteroids and bile acids using NAD(+) as the preferred coenzyme at an optimal pH of 7.4-9.5, and was inhibited by ketamine and organic anions. The mRNA for AKR1C17 was detected specifically in rat kidney, where the enzyme was more highly expressed as a cytosolic protein than NADP(H)-dependent 3alpha-HSD (AKR1C9). Thus, AKR1C17 represents a novel NAD(+)-dependent type of cytosolic 3alpha-HSD with unique inhibitor sensitivity and tissue distribution. In addition, the replacement of Gln270 and Glu276 of AKR1C17 with the corresponding residues of NADP(H)-dependent 3alpha-HSD resulted in a switch in favor of NADP(+) specificity, suggesting their key roles in coenzyme specificity.

  19. Human and rodent aldo-keto reductases from the AKR1B subfamily and their specificity with retinaldehyde

    PubMed Central

    Ruiz, F. Xavier; Moro, Armando; Gallego, Oriol; Ardèvol, Albert; Rovira, Carme; Petrash, J. Mark; Parés, Xavier; Farrés, Jaume

    2011-01-01

    NADP(H)-dependent cytosolic aldo-keto reductases (AKR) are mostly monomeric enzymes which fold into a typical (α/β)8-barrel structure. Substrate specificity and inhibitor selectivity are determined by interaction with residues located in three highly variable loops (A, B, and C). Based on sequence identity, AKR have been grouped into families, namely AKR1–AKR15, containing multiple subfamilies. Two human enzymes from the AKR1B subfamily (AKR1B1 and AKR1B10) are of special interest. AKR1B1 (aldose reductase) is related to secondary diabetic complications, while AKR1B10 is induced in cancer cells and is highly active with all-trans-retinaldehyde. Residues interacting with all-trans-retinaldehyde and differing between AKR1B1 and AKR1B10 are Leu125Lys and Val131Ala (loop A), Leu301Val, Ser303Gln, and Cys304Ser (loop C). Recently, we demonstrated the importance of Lys125 as a determinant of AKR1B10 specificity for retinoids. Residues 301 and 304 are also involved in interactions with substrates or inhibitors, and thus we checked their contribution to retinoid specificity. We also extended our study with retinoids to rodent members of the AKR1B subfamily: AKR1B3 (aldose reductase), AKR1B7 (mouse vas deferens protein), AKR1B8 (fibroblast-growth factor 1-regulated protein), and AKR1B9 (Chinese hamster ovary reductase), which were tested against all-trans isomers of retinaldehyde and retinol. All enzymes were active with retinaldehyde, but with kcat values (0.02–0.52 min−1) much lower than that of AKR1B10 (27 min−1). None of the enzymes showed oxidizing activity with retinol. Since these enzymes (except AKR1B3) have Lys125, other residues should account for retinaldehyde specificity. Here, by using site-directed mutagenesis and molecular modeling, we further delineate the contribution of residues 301 and 304. We demonstrate that besides Lys125, Ser304 is a major structural determinant for all-trans-retinaldehyde specificity of AKR1B10. PMID:21329680

  20. Anthracycline resistance mediated by reductive metabolism in cancer cells: The role of aldo-keto reductase 1C3

    SciTech Connect

    Hofman, Jakub; Malcekova, Beata; Skarka, Adam; Novotna, Eva; Wsol, Vladimir

    2014-08-01

    Pharmacokinetic drug resistance is a serious obstacle that emerges during cancer chemotherapy. In this study, we investigated the possible role of aldo-keto reductase 1C3 (AKR1C3) in the resistance of cancer cells to anthracyclines. First, the reducing activity of AKR1C3 toward anthracyclines was tested using incubations with a purified recombinant enzyme. Furthermore, the intracellular reduction of daunorubicin and idarubicin was examined by employing the transfection of A549, HeLa, MCF7 and HCT 116 cancer cells with an AKR1C3 encoding vector. To investigate the participation of AKR1C3 in anthracycline resistance, we conducted MTT cytotoxicity assays with these cells, and observed that AKR1C3 significantly contributes to the resistance of cancer cells to daunorubicin and idarubicin, whereas this resistance was reversible by the simultaneous administration of 2′-hydroxyflavanone, a specific AKR1C3 inhibitor. In the final part of our work, we tracked the changes in AKR1C3 expression after anthracycline exposure. Interestingly, a reciprocal correlation between the extent of induction and endogenous levels of AKR1C3 was recorded in particular cell lines. Therefore, we suggest that the induction of AKR1C3 following exposure to daunorubicin and idarubicin, which seems to be dependent on endogenous AKR1C3 expression, eventually might potentiate an intrinsic resistance given by the normal expression of AKR1C3. In conclusion, our data suggest a substantial impact of AKR1C3 on the metabolism of daunorubicin and idarubicin, which affects their pharmacokinetic and pharmacodynamic behavior. In addition, we demonstrate that the reduction of daunorubicin and idarubicin, which is catalyzed by AKR1C3, contributes to the resistance of cancer cells to anthracycline treatment. - Highlights: • Metabolism of anthracyclines by AKR1C3 was studied at enzyme and cellular levels. • Anthracycline resistance mediated by AKR1C3 was demonstrated in cancer cells. • Induction of AKR1C3

  1. The role of cytochromes p450 and aldo-keto reductases in prognosis of breast carcinoma patients.

    PubMed

    Hlaváč, Viktor; Brynychová, Veronika; Václavíková, Radka; Ehrlichová, Marie; Vrána, David; Pecha, Václav; Trnková, Markéta; Kodet, Roman; Mrhalová, Marcela; Kubáčková, Kateřina; Gatěk, Jiří; Vážan, Petr; Souček, Pavel

    2014-12-01

    Metabolism of anticancer drugs affects their antitumor effects. This study has investigated the associations of gene expression of enzymes metabolizing anticancer drugs with therapy response and survival of breast carcinoma patients. Gene expression of 13 aldo-keto reductases (AKRs), carbonyl reductase 1, and 10 cytochromes P450 (CYPs) was assessed using quantitative real-time polymerase chain reaction in tumors and paired adjacent nonneoplastic tissues from 68 posttreatment breast carcinoma patients. Eleven candidate genes were then evaluated in an independent series of 50 pretreatment patients. Protein expression of the most significant genes was confirmed by immunoblotting. AKR1A1 was significantly overexpressed and AKR1C1-4, KCNAB1, CYP2C19, CYP3A4, and CYP3A5 downregulated in tumors compared with control nonneoplastic tissues after correction for multiple testing. Significant association of CYP2B6 transcript levels in tumors with expression of hormonal receptors was found in the posttreatment set and replicated in the pretreatment set of patients. Significantly higher intratumoral levels of AKR1C1, AKR1C2, or CYP2W1 were found in responders to neoadjuvant chemotherapy compared with nonresponders. Patients with high AKR7A3 or CYP2B6 levels in the pretreatment set had significantly longer disease-free survival than patients with low levels. Protein products of AKR1C1, AKR1C2, AKR7A3, CYP3A4, and carbonyl reductase (CBR1) were found in tumors and those of AKR1C1, AKR7A3, and CBR1 correlated with their transcript levels. Small interfering RNA-directed knockdown of AKR1C2 or vector-mediated upregulation of CYP3A4 in MDA-MB-231 model cell line had no effect on cell proliferation after paclitaxel treatment in vitro. Prognostic and predictive roles of drug-metabolizing enzymes strikingly differ between posttreatment and pretreatment breast carcinoma patients. Mechanisms of action of AKR1C2, AKR7A3, CYP2B6, CYP3A4, and CBR1 should continue to be further followed in

  2. The Role of Human Aldo-Keto Reductases in the Metabolic Activation and Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH Catechols and PAH o-Quinones.

    PubMed

    Zhang, Li; Jin, Yi; Huang, Meng; Penning, Trevor M

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants. They are procarcinogens requiring metabolic activation to elicit their deleterious effects. Aldo-keto reductases (AKR) catalyze the oxidation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active PAH o-quinones. AKRs are also found to be capable of reducing PAH o-quinones to form PAH catechols. The interconversion of o-quinones and catechols results in the redox-cycling of PAH o-quinones to give rise to the generation of reactive oxygen species and subsequent oxidative DNA damage. On the other hand, PAH catechols can be intercepted through phase II metabolism by which PAH o-quinones could be detoxified and eliminated. The aim of the present review is to summarize the role of human AKRs in the metabolic activation/detoxication of PAH and the relevance of phase II conjugation reactions to human lung carcinogenesis.

  3. cDNA cloning, expression and activity of a second human aflatoxin B1-metabolizing member of the aldo-keto reductase superfamily, AKR7A3.

    PubMed

    Knight, L P; Primiano, T; Groopman, J D; Kensler, T W; Sutter, T R

    1999-07-01

    The aflatoxin B1 (AFB1) aldehyde metabolite of AFB1 may contribute to the cytotoxicity of this hepatocarcinogen via protein adduction. Aflatoxin B1 aldehyde reductases, specifically the NADPH-dependent aldo-keto reductases of rat (AKR7A1) and human (AKR7A2), are known to metabolize the AFB1 dihydrodiol by forming AFB1 dialcohol. Using a rat AKR7A1 cDNA, we isolated and characterized a distinct aldo-keto reductase (AKR7A3) from an adult human liver cDNA library. The deduced amino acid sequence of AKR7A3 shares 80 and 88% identity with rat AKR7A1 and human AKR7A2, respectively. Recombinant rat AKR7A1 and human AKR7A3 were expressed and purified from Escherichia coli as hexa-histidine tagged fusion proteins. These proteins catalyzed the reduction of several model carbonyl-containing substrates. The NADPH-dependent formation of AFB1 dialcohol by recombinant human AKR7A3 was confirmed by liquid chromatography coupled to electrospray ionization mass spectrometry. Rabbit polyclonal antibodies produced using recombinant rat AKR7A1 protein were shown to detect nanogram amounts of rat and human AKR7A protein. The amount of AKR7A-related protein in hepatic cytosols of 1, 2-dithiole-3-thione-treated rats was 18-fold greater than in cytosols from untreated animals. These antibodies detected AKR7A-related protein in normal human liver samples ranging from 0.3 to 0.8 microg/mg cytosolic protein. Northern blot analysis showed varying levels of expression of AKR7A RNA in human liver and in several extrahepatic tissues, with relatively high levels in the stomach, pancreas, kidney and liver. Based on the kinetic parameters determined using recombinant human AKR7A3 and AFB1 dihydrodiol at pH 7.4, the catalytic efficiency of this reaction (k2/K, per M/s) equals or exceeds those reported for other enzymes, for example cytochrome P450s and glutathione S-transferases, known to metabolize AFB1 in vivo. These findings indicate that, depending on the extent of AFB1 dihydrodiol formation, AKR

  4. A novel aldo-keto reductase from Jatropha curcas L. (JcAKR) plays a crucial role in the detoxification of methylglyoxal, a potent electrophile.

    PubMed

    Mudalkar, Shalini; Sreeharsha, Rachapudi Venkata; Reddy, Attipalli Ramachandra

    2016-05-20

    Abiotic stress leads to the generation of reactive oxygen species (ROS) which further results in the production of reactive carbonyls (RCs) including methylglyoxal (MG). MG, an α, β-dicarbonyl aldehyde, is highly toxic to plants and the mechanism behind its detoxification is not well understood. Aldo-keto reductases (AKRs) play a role in detoxification of reactive aldehydes and ketones. In the present study, we cloned and characterised a putative AKR from Jatropha curcas (JcAKR). Phylogenetically, it forms a small clade with AKRs of Glycine max and Rauwolfia serpentina. JcAKR was heterologously expressed in Escherichia coli BL-21(DE3) cells and the identity of the purified protein was confirmed through MALDI-TOF analysis. The recombinant protein had high enzyme activity and catalytic efficiency in assays containing MG as the substrate. Protein modelling and docking studies revealed MG was efficiently bound to JcAKR. Under progressive drought and salinity stress, the enzyme and transcript levels of JcAKR were higher in leaves compared to roots. Further, the bacterial and yeast cells expressing JcAKR showed more tolerance towards PEG (5%), NaCl (200mM) and MG (5mM) treatments compared to controls. In conclusion, our results project JcAKR as a possible and potential target in crop improvement for abiotic stress tolerance. PMID:26995646

  5. The Aldo-Keto Reductase AKR1B10 Is Up-Regulated in Keloid Epidermis, Implicating Retinoic Acid Pathway Dysregulation in the Pathogenesis of Keloid Disease.

    PubMed

    Jumper, Natalie; Hodgkinson, Tom; Arscott, Guyan; Har-Shai, Yaron; Paus, Ralf; Bayat, Ardeshir

    2016-07-01

    Keloid disease is a recurrent fibroproliferative cutaneous tumor of unknown pathogenesis for which clinical management remains unsatisfactory. To obtain new insights into hitherto underappreciated aspects of keloid pathobiology, we took a laser capture microdissection-based, whole-genome microarray analysis approach to identify distinct keloid disease-associated gene expression patterns within defined keloid regions. Identification of the aldo-keto reductase enzyme AKR1B10 as highly up-regulated in keloid epidermis suggested that an imbalance of retinoic acid metabolism is likely associated with keloid disease. Here, we show that AKR1B10 transfection into normal human keratinocytes reproduced the abnormal retinoic acid pathway expression pattern we had identified in keloid epidermis. Cotransfection of AKR1B10 with a luciferase reporter plasmid showed reduced retinoic acid response element activity, supporting the hypothesis of retinoic acid synthesis deficiency in keloid epidermis. Paracrine signals released by AKR1B10-overexpressing keratinocytes into conditioned medium resulted in up-regulation of transforming growth factor-β1, transforming growth factor-β2, and collagens I and III in both keloid and normal skin fibroblasts, mimicking the typical profibrotic keloid profile. Our study results suggest that insufficient retinoic acid synthesis by keloid epidermal keratinocytes may contribute to the pathogenesis of keloid disease. We refocus attention on the role of injured epithelium in keloid disease and identify AKR1B10 as a potential new target in future management of keloid disease. PMID:27025872

  6. Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor.

    PubMed

    Adeniji, Adegoke; Uddin, Md Jashim; Zang, Tianzhu; Tamae, Daniel; Wangtrakuldee, Phumvadee; Marnett, Lawrence J; Penning, Trevor M

    2016-08-25

    Type 5 17β-hydroxysteroid dehydrogenase, aldo-keto reductase 1C3 (AKR1C3) converts Δ(4)-androstene-3,17-dione and 5α-androstane-3,17-dione to testosterone (T) and 5α-dihydrotestosterone, respectively, in castration resistant prostate cancer (CRPC). In CRPC, AKR1C3 is implicated in drug resistance, and enzalutamide drug resistance can be surmounted by indomethacin a potent inhibitor of AKR1C3. We examined a series of naproxen analogues and find that (R)-2-(6-methoxynaphthalen-2-yl)butanoic acid (in which the methyl group of R-naproxen was replaced by an ethyl group) acts as a potent AKR1C3 inhibitor that displays selectivity for AKR1C3 over other AKR1C enzymes. This compound was devoid of inhibitory activity on COX isozymes and blocked AKR1C3 mediated production of T and induction of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line. R-Profens are substrate selective COX-2 inhibitors and block the oxygenation of endocannabinoids and in the context of advanced prostate cancer R-profens could inhibit intratumoral androgen synthesis and act as analgesics for metastatic disease.

  7. Aldo-keto reductase 1C1 induced by interleukin-1β mediates the invasive potential and drug resistance of metastatic bladder cancer cells

    PubMed Central

    Matsumoto, Ryuji; Tsuda, Masumi; Yoshida, Kazuhiko; Tanino, Mishie; Kimura, Taichi; Nishihara, Hiroshi; Abe, Takashige; Shinohara, Nobuo; Nonomura, Katsuya; Tanaka, Shinya

    2016-01-01

    In treating bladder cancer, determining the molecular mechanisms of tumor invasion, metastasis, and drug resistance are urgent to improving long-term patient survival. One of the metabolic enzymes, aldo-keto reductase 1C1 (AKR1C1), plays an essential role in cancer invasion/metastasis and chemoresistance. In orthotopic xenograft models of a human bladder cancer cell line, UM-UC-3, metastatic sublines were established from tumors in the liver, lung, and bone. These cells possessed elevated levels of EMT-associated markers, such as Snail, Slug, or CD44, and exhibited enhanced invasion. By microarray analysis, AKR1C1 was found to be up-regulated in metastatic lesions, which was verified in metastatic human bladder cancer specimens. Decreased invasion caused by AKR1C1 knockdown suggests a novel role of AKR1C1 in cancer invasion, which is probably due to the regulation of Rac1, Src, or Akt. An inflammatory cytokine, interleukin-1β, was found to increase AKR1C1 in bladder cancer cell lines. One particular non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic sublines. These data uncover the crucial role of AKR1C1 in regulating both metastasis and drug resistance; as a result, AKR1C1 should be a potent molecular target in invasive bladder cancer treatment. PMID:27698389

  8. Aldo-keto reductase family 1 B10 protein detoxifies dietary and lipid-derived alpha, beta-unsaturated carbonyls at physiological levels

    SciTech Connect

    Zhong, Linlin; Liu, Ziwen; Yan, Ruilan; Johnson, Stephen; Zhao, Yupei; Fang, Xiubin; Cao, Deliang

    2009-09-18

    Alpha, beta-unsaturated carbonyls are highly reactive mutagens and carcinogens to which humans are exposed on a daily basis. This study demonstrates that aldo-keto reductase family 1 member B10 (AKR1B10) is a critical protein in detoxifying dietary and lipid-derived unsaturated carbonyls. Purified AKR1B10 recombinant protein efficiently catalyzed the reduction to less toxic alcohol forms of crotonaldehyde at 0.90 {mu}M, 4-hydroxynonenal (HNE) at 0.10 {mu}M, trans-2-hexanal at 0.10 {mu}M, and trans-2,4-hexadienal at 0.05 {mu}M, the concentrations at or lower than physiological exposures. Ectopically expressed AKR1B10 in 293T cells eliminated immediately HNE at 1 (subtoxic) or 5 {mu}M (toxic) by converting to 1,4-dihydroxynonene, protecting the cells from HNE toxicity. AKR1B10 protein also showed strong enzymatic activity toward glutathione-conjugated carbonyls. Taken together, our study results suggest that AKR1B10 specifically expressed in the intestine is physiologically important in protecting the host cell against dietary and lipid-derived cytotoxic carbonyls.

  9. An ethoxyquin-inducible aldehyde reductase from rat liver that metabolizes aflatoxin B1 defines a subfamily of aldo-keto reductases.

    PubMed

    Ellis, E M; Judah, D J; Neal, G E; Hayes, J D

    1993-11-01

    Protection of liver against the toxic and carcinogenic effects of aflatoxin B1 (AFB1) can be achieved through the induction of detoxification enzymes by chemoprotectors such as the phenolic antioxidant ethoxyquin. We have cloned and sequenced a cDNA encoding an aldehyde reductase (AFB1-AR), which is expressed in rat liver in response to dietary ethoxyquin. Expression of the cDNA in Escherichia coli and purification of the recombinant enzyme reveals that the protein exhibits aldehyde reductase activity and is capable of converting the protein-binding dialdehyde form of AFB1-dihydrodiol to the nonbinding dialcohol metabolite. We show that the mRNA encoding this enzyme is markedly elevated in the liver of rats fed an ethoxyquin-containing diet, correlating with acquisition of resistance to AFB1. AFB1-AR represents the only carcinogen-metabolizing aldehyde reductase identified to date that is induced by a chemoprotector. Alignment of the amino acid sequence of AFB1-AR with other known and putative aldehyde reductases shows that it defines a subfamily within the aldo-keto reductase superfamily. PMID:8234296

  10. The Grid Enabled Mass Storage System (GEMSS): the Storage and Data management system used at the INFN Tier1 at CNAF.

    NASA Astrophysics Data System (ADS)

    Ricci, Pier Paolo; Bonacorsi, Daniele; Cavalli, Alessandro; Dell'Agnello, Luca; Gregori, Daniele; Prosperini, Andrea; Rinaldi, Lorenzo; Sapunenko, Vladimir; Vagnoni, Vincenzo

    2012-12-01

    The storage system currently used in production at the INFN Tier1 at CNAF is the result of several years of case studies, software development and tests. This solution, called the Grid Enabled Mass Storage System (GEMSS), is based on a custom integration between a fast and reliable parallel filesystem (the IBM General Parallel File System, GPFS), with a complete integrated tape backend based on the Tivoli Storage Manager (TSM), which provides Hierarchical Storage Management (HSM) capabilities, and the Grid Storage Resource Manager (StoRM), providing access to grid users through a standard SRM interface. Since the start of the Large Hadron Collider (LHC) operation, all LHC experiments have been using GEMSS at CNAF for both disk data access and long-term archival on tape media. Moreover, during last year, GEMSS has become the standard solution for all other experiments hosted at CNAF, allowing the definitive consolidation of the data storage layer. Our choice has proved to be very successful during the last two years of production with continuous enhancements, accurate monitoring and effective customizations according to the end-user requests. In this paper a description of the system is reported, addressing recent developments and giving an overview of the administration and monitoring tools. We also discuss the solutions adopted in order to grant the maximum availability of the service and the latest optimization features within the data access process. Finally, we summarize the main results obtained during these last years of activity from the perspective of some of the end-users, showing the reliability and the high performances that can be achieved using GEMSS.

  11. The rate-determining steps of aldo-keto reductases (AKRs), a study on human steroid 5β-reductase (AKR1D1).

    PubMed

    Chen, Mo; Jin, Yi; Penning, Trevor M

    2015-06-01

    Aldo-keto reductases (AKRs) are an expanding family of NAD(P)(H)-dependent oxidoreductases that catalyze the reduction of either carbonyl groups or α,β-unsaturated ketones on a variety of endogenous and exogenous substrates. The enzymes catalyze a sequential ordered bi-bi kinetic mechanism, in which cofactor is bound first and released last. Using human steroid 5β-reductase (AKR1D1) as a representative enzyme, the influence of substrate structure on the rate-limiting steps of AKR catalysis has been previously determined. The rate of the chemistry step was found to differ by two orders of magnitude when different steroid substrates were used in single turnover experiments with AKR1D1. This difference was reflected in multiple turnover experiments. C17-C21 steroid substrates exhibited a fast chemistry step followed by slow product release as suggested by "burst" phase kinetics. By contrast, C27 steroids have a slower chemical step that determines the rate of the reaction and "burst-phase" kinetics are no longer observed. Here we present single turnover kinetic experiments and find that they support the existence of two different binding poses for fast substrates due to their biphasic nature. We also re-interpret the loss of "burst-phase" kinetics in the multiple turnover experiments as due to long range effects of the steroid side-chain interacting with distal parts of the steroid pocket to perturb the reaction trajectory for hydride transfer and thus reduce kcat. The ability of steroid structure and hence binding pose to influence rate determination in steroid transforming AKRs is discussed as a general phenomenon.

  12. Comparative functional analysis of human medium-chain dehydrogenases, short-chain dehydrogenases/reductases and aldo-keto reductases with retinoids

    PubMed Central

    Gallego, Oriol; Belyaeva, Olga V.; Porté, Sergio; Ruiz, F. Xavier; Stetsenko, Anton V.; Shabrova, Elena V.; Kostereva, Natalia V.; Farrés, Jaume; Parés, Xavier; Kedishvili, Natalia Y.

    2006-01-01

    Retinoic acid biosynthesis in vertebrates occurs in two consecutive steps: the oxidation of retinol to retinaldehyde followed by the oxidation of retinaldehyde to retinoic acid. Enzymes of the MDR (medium-chain dehydrogenase/reductase), SDR (short-chain dehydrogenase/reductase) and AKR (aldo-keto reductase) superfamilies have been reported to catalyse the conversion between retinol and retinaldehyde. Estimation of the relative contribution of enzymes of each type was difficult since kinetics were performed with different methodologies, but SDRs would supposedly play a major role because of their low Km values, and because they were found to be active with retinol bound to CRBPI (cellular retinol binding protein type I). In the present study we employed detergent-free assays and HPLC-based methodology to characterize side-by-side the retinoid-converting activities of human MDR [ADH (alcohol dehydrogenase) 1B2 and ADH4), SDR (RoDH (retinol dehydrogenase)-4 and RDH11] and AKR (AKR1B1 and AKR1B10) enzymes. Our results demonstrate that none of the enzymes, including the SDR members, are active with CRBPI-bound retinoids, which questions the previously suggested role of CRBPI as a retinol supplier in the retinoic acid synthesis pathway. The members of all three superfamilies exhibit similar and low Km values for retinoids (0.12–1.1 μM), whilst they strongly differ in their kcat values, which range from 0.35 min−1 for AKR1B1 to 302 min−1 for ADH4. ADHs appear to be more effective retinol dehydrogenases than SDRs because of their higher kcat values, whereas RDH11 and AKR1B10 are efficient retinaldehyde reductases. Cell culture studies support a role for RoDH-4 as a retinol dehydrogenase and for AKR1B1 as a retinaldehyde reductase in vivo. PMID:16787387

  13. Acquisition of doxorubicin resistance facilitates migrating and invasive potentials of gastric cancer MKN45 cells through up-regulating aldo-keto reductase 1B10.

    PubMed

    Morikawa, Yoshifumi; Kezuka, Chihiro; Endo, Satoshi; Ikari, Akira; Soda, Midori; Yamamura, Keiko; Toyooka, Naoki; El-Kabbani, Ossama; Hara, Akira; Matsunaga, Toshiyuki

    2015-03-25

    Continuous exposure to doxorubicin (DOX) accelerates hyposensitivity to the drug-elicited lethality of gastric cells, with increased risks of the recurrence and serious cardiovascular side effects. However, the detailed mechanisms underlying the reduction of DOX sensitivity remain unclear. In this study, we generated a DOX-resistant variant upon continuously treating human gastric cancer MKN45 cells with incremental concentrations of the drug, and investigated whether the gain of DOX resistance influences gene expression of four aldo-keto reductases (AKRs: 1B10, 1C1, 1C2 and 1C3). RT-PCR analysis revealed that among the enzymes AKR1B10 is most highly up-regulated during the chemoresistance induction. The up-regulation of AKR1B10 was confirmed by analyses of Western blotting and enzyme activity. The DOX sensitivity of MKN45 cells was reduced and elevated by overexpression and inhibition of AKR1B10, respectively. Compared to the parental MKN45 cells, the DOX-resistant cells had higher migrating and invasive abilities, which were significantly suppressed by addition of AKR1B10 inhibitors. Zymographic and real-time PCR analyses also revealed significant increases in secretion and expression of matrix metalloproteinase (MMP) 2 associated with DOX resistance. Moreover, the overexpression of AKR1B10 in the parental cells remarkably facilitated malignant progression (elevation of migrating and invasive potentials) and MMP2 secretion, which were lowered by the AKR1B10 inhibitors. These results suggest that AKR1B10 is a DOX-resistance gene in the gastric cancer cells, and is responsible for elevating the migrating and invasive potentials of the cells through induction of MMP2. PMID:25686905

  14. Plant aldo-keto reductases (AKRs) as multi-tasking soldiers involved in diverse plant metabolic processes and stress defense: A structure-function update.

    PubMed

    Sengupta, Debashree; Naik, Dhiraj; Reddy, Attipalli R

    2015-05-01

    The aldo-keto reductase (AKR) superfamily comprises of a large number of primarily monomeric protein members, which reduce a broad spectrum of substrates ranging from simple sugars to potentially toxic aldehydes. Plant AKRs can be broadly categorized into four important functional groups, which highlight their roles in diverse plant metabolic reactions including reactive aldehyde detoxification, biosynthesis of osmolytes, secondary metabolism and membrane transport. Further, multiple overlapping functional aspects of plant AKRs including biotic and abiotic stress defense, production of commercially important secondary metabolites, iron acquisition from soil, plant-microbe interactions etc. are discussed as subcategories within respective major groups. Owing to the broad substrate specificity and multiple stress tolerance of the well-characterized AKR4C9 from Arabidopsis thaliana, protein sequences of all the homologues of AKR4C9 (A9-like proteins) from forty different plant species (Phytozome database) were analyzed. The analysis revealed that all A9-like proteins possess strictly conserved key catalytic residues (D-47, Y-52 and K-81) and belong to the pfam00248 and cl00470 AKR superfamilies. Based on structural homology of the three flexible loops of AKR4C9 (Loop A, B and C) responsible for broad substrate specificity, A9-like proteins found in Brassica rapa, Phaseolus vulgaris, Cucumis sativus, Populus trichocarpa and Solanum lycopersicum were predicted to have a similar range of substrate specificity. Thus, plant AKRs can be considered as potential breeding targets for developing stress tolerant varieties in the future. The present review provides a consolidated update on the current research status of plant AKRs with an emphasis on important functional aspects as well as their potential future prospects and an insight into the overall structure-function relationships of A9-like proteins.

  15. Plant aldo-keto reductases (AKRs) as multi-tasking soldiers involved in diverse plant metabolic processes and stress defense: A structure-function update.

    PubMed

    Sengupta, Debashree; Naik, Dhiraj; Reddy, Attipalli R

    2015-05-01

    The aldo-keto reductase (AKR) superfamily comprises of a large number of primarily monomeric protein members, which reduce a broad spectrum of substrates ranging from simple sugars to potentially toxic aldehydes. Plant AKRs can be broadly categorized into four important functional groups, which highlight their roles in diverse plant metabolic reactions including reactive aldehyde detoxification, biosynthesis of osmolytes, secondary metabolism and membrane transport. Further, multiple overlapping functional aspects of plant AKRs including biotic and abiotic stress defense, production of commercially important secondary metabolites, iron acquisition from soil, plant-microbe interactions etc. are discussed as subcategories within respective major groups. Owing to the broad substrate specificity and multiple stress tolerance of the well-characterized AKR4C9 from Arabidopsis thaliana, protein sequences of all the homologues of AKR4C9 (A9-like proteins) from forty different plant species (Phytozome database) were analyzed. The analysis revealed that all A9-like proteins possess strictly conserved key catalytic residues (D-47, Y-52 and K-81) and belong to the pfam00248 and cl00470 AKR superfamilies. Based on structural homology of the three flexible loops of AKR4C9 (Loop A, B and C) responsible for broad substrate specificity, A9-like proteins found in Brassica rapa, Phaseolus vulgaris, Cucumis sativus, Populus trichocarpa and Solanum lycopersicum were predicted to have a similar range of substrate specificity. Thus, plant AKRs can be considered as potential breeding targets for developing stress tolerant varieties in the future. The present review provides a consolidated update on the current research status of plant AKRs with an emphasis on important functional aspects as well as their potential future prospects and an insight into the overall structure-function relationships of A9-like proteins. PMID:25840343

  16. Transcriptional regulation of aldo-keto reductase 1C1 in HT29 human colon cancer cells resistant to methotrexate: role in the cell cycle and apoptosis.

    PubMed

    Selga, Elisabet; Noé, Véronique; Ciudad, Carlos J

    2008-01-15

    While studying differentially expressed genes between sensitive and 10(-5)M Methotrexate (MTX) resistant HT29 human colon cancer cells, we identified some members of the aldo-keto reductase (AKR) superfamily. The study was followed with the member AKR1C1 (EC 1.1.1.213), validating its increase in mRNA and protein levels in MTX resistant cells. The genomic content for AKR1C1 remained unchanged between sensitive and resistant cells, thereby excluding a mechanism of AKR1C1 gene amplification. Thus, we cloned the AKR1C1 human promoter and performed luciferase experiments that revealed a transcriptional regulation of the gene in the resistant cells. Computational studies showed a putative binding site for the transcription factor Sp1. The co-transfection of Sp1 or Sp3 with different constructs of AKR1C1 promoter deletions, including and excluding the proximal GC-box, demonstrated a key role for these factors in regulating AKR1C1 transcriptional activity. Gel-shift assays revealed an increase in Sp1 and Sp3 binding in resistant compared to sensitive cells, without differences in Sp1 protein levels. Dephosphorylation of the extracts coincided with a decrease in Sp1 binding, which is consistent with a process of regulation of Sp1 by phosphorylation. We also investigated the possible relationship between AKR1C1 expression and MTX action. Overexpression of AKR1C1 counteracted the S-phase accumulation of cells and apoptosis caused by MTX treatment. This suggests a role of AKR1C1 in cell proliferation. Finally, overexpression of AKR1C1 in MTX sensitive HT29 cells conferred resistance to the chemotherapeutic agent and silencing of AKR1C1 by means of iRNA technology sensitized the cells to MTX.

  17. Sequence analysis of frog rho-crystallin by cDNA cloning and sequencing: a member of the aldo-keto reductase family.

    PubMed

    Lu, S F; Pan, F M; Chiou, S H

    1995-09-25

    rho-Crystallin is a major enzyme crystallin present in the lenses of amphibian species with a blocked amino terminus. In order to facilitate the determination of the primary sequence of this taxon-specific crystallin, cDNA mixture was synthesized from the poly(A)+mRNA of bullfrog eye lenses. cDNAs encoding rho-crystallin were then amplified by polymerase chain reaction (PCR) using a new protocol of Rapid Amplification of cDNA Ends (RACE). PCR-amplified product corresponding to rho-crystallin was obtained, which was then subcloned into pUC18 vector and then transformed into E. coli strain JM109. Plasmids purified from the positive clones were prepared for nucleotide sequencing by the automatic fluorescence-based dideoxynucleotide chain-termination method. Sequencing more than 15 clones containing DNA inserts coding for rho-crystallin constructed only one unique and complete full-length reading frame of 975 base pairs covering a deduced protein sequence of 324 amino acids including the universal initiating methionine. It shows 96, 59, 46 and 37 percent sequence similarity to another rho-crystallin from European common frog, bovine prostaglandin-F synthase, human aldose reductase and human aldehyde reductase, respectively, revealing the close relationship between rho-crystallins from related amphibian species and its possible evolutionary relatedness with various aldo-keto reductases. In this study a phylogenetic tree for rho-crystallin and related enzymes is constructed based on multiple-sequence alignment program using a combination of distance matrix and approximate parsimony methods. We have thus established the remote phylogenetic relationship between rho-crystallin and some aldehyde/aldose reductases, which may provide a possible link for the recruitment of this crystallin from detoxification-related enzymes and its physiological role in maintaining a transparent and clear lens.

  18. Fluoxetine elevates allopregnanolone in female rat brain but inhibits a steroid microsomal dehydrogenase rather than activating an aldo-keto reductase

    PubMed Central

    Fry, J P; Li, K Y; Devall, A J; Cockcroft, S; Honour, J W; Lovick, T A

    2014-01-01

    Background and Purpose Fluoxetine, a selective serotonin reuptake inhibitor, elevates brain concentrations of the neuroactive progesterone metabolite allopregnanolone, an effect suggested to underlie its use in the treatment of premenstrual dysphoria. One report showed fluoxetine to activate the aldo-keto reductase (AKR) component of 3α-hydroxysteroid dehydrogenase (3α-HSD), which catalyses production of allopregnanolone from 5α-dihydroprogesterone. However, this action was not observed by others. The present study sought to clarify the site of action for fluoxetine in elevating brain allopregnanolone. Experimental Approach Adult male rats and female rats in dioestrus were treated with fluoxetine and their brains assayed for allopregnanolone and its precursors, progesterone and 5α-dihydroprogesterone. Subcellular fractions of rat brain were also used to investigate the actions of fluoxetine on 3α-HSD activity in both the reductive direction, producing allopregnanolone from 5α-dihydroprogesterone, and the reverse oxidative direction. Fluoxetine was also tested on these recombinant enzyme activities expressed in HEK cells. Key Results Short-term treatment with fluoxetine increased brain allopregnanolone concentrations in female, but not male, rats. Enzyme assays on native rat brain fractions and on activities expressed in HEK cells showed fluoxetine did not affect the AKR producing allopregnanolone from 5α-dihydroprogesterone but did inhibit the microsomal dehydrogenase oxidizing allopregnanolone to 5α-dihydroprogesterone. Conclusions and Implications Fluoxetine elevated allopregnanolone in female rat brain by inhibiting its oxidation to 5α-dihydroprogesterone by a microsomal dehydrogenase. This is a novel site of action for fluoxetine, with implications for the development of new agents and/or dosing regimens to raise brain allopregnanolone. PMID:25161074

  19. Exposure to 9,10-phenanthrenequinone accelerates malignant progression of lung cancer cells through up-regulation of aldo-keto reductase 1B10

    SciTech Connect

    Matsunaga, Toshiyuki; Morikawa, Yoshifumi; Haga, Mariko; Endo, Satoshi; Soda, Midori; Yamamura, Keiko; El-Kabbani, Ossama; Tajima, Kazuo; Ikari, Akira; Hara, Akira

    2014-07-15

    Inhalation of 9,10-phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust, exerts fatal damage against a variety of cells involved in respiratory function. Here, we show that treatment with high concentrations of 9,10-PQ evokes apoptosis of lung cancer A549 cells through production of reactive oxygen species (ROS). In contrast, 9,10-PQ at its concentrations of 2 and 5 μM elevated the potentials for proliferation, invasion, metastasis and tumorigenesis, all of which were almost completely inhibited by addition of an antioxidant N-acetyl-L-cysteine, inferring a crucial role of ROS in the overgrowth and malignant progression of lung cancer cells. Comparison of mRNA expression levels of six aldo-keto reductases (AKRs) in the 9,10-PQ-treated cells advocated up-regulation of AKR1B10 as a major cause contributing to the lung cancer malignancy. In support of this, the elevation of invasive, metastatic and tumorigenic activities in the 9,10-PQ-treated cells was significantly abolished by the addition of a selective AKR1B10 inhibitor oleanolic acid. Intriguingly, zymographic and real-time PCR analyses revealed remarkable increases in secretion and expression, respectively, of matrix metalloproteinase 2 during the 9,10-PQ treatment, and suggested that the AKR1B10 up-regulation and resultant activation of mitogen-activated protein kinase cascade are predominant mechanisms underlying the metalloproteinase induction. In addition, HPLC analysis and cytochrome c reduction assay in in vitro 9,10-PQ reduction by AKR1B10 demonstrated that the enzyme catalyzes redox-cycling of this quinone, by which ROS are produced. Collectively, these results suggest that AKR1B10 is a key regulator involved in overgrowth and malignant progression of the lung cancer cells through ROS production due to 9,10-PQ redox-cycling. - Highlights: • 9,10-PQ promotes invasion, metastasis and tumorigenicity in lung cancer cells. • The 9,10-PQ-elicited promotion is possibly due to AKR1B10 up

  20. The role of aldo-keto reductase 1C3 (AKR1C3)-mediated prostaglandin D2 (PGD2) metabolism in keloids.

    PubMed

    Mantel, Alon; Newsome, Austin; Thekkudan, Theresa; Frazier, Robert; Katdare, Meena

    2016-01-01

    Keloids are progressively expanding scars, mostly prevalent in individuals of African descent. Previous data identified increased mast cell number and activation state in keloids suggesting a role in disease progression. The major eicosanoid secreted by mast cells is prostaglandin D2 (PGD2), a relatively unstable pro-inflammatory mediator which can be spontaneously converted to 15-deoxy-(Delta12,14)-prostaglandin J2(15d-PGJ2) or enzymatically metabolized to 9α,11β-PGF2 by aldo-keto reductase 1C3 (AKR1C3). In this work, we investigated the possible role of PGD2 and its metabolites in keloids using CRL1762 keloid fibroblasts (KF) and immunohistochemical staining. Our data suggested approximately 3-fold increase of tryptase-positive mast cell count in keloids compared with normal skin. Furthermore, AKR1C3 was overexpressed in the fibrotic area of keloids while relatively weak staining detected in normal skin. Metabolism of PGD2 to 9α,11β-PGF2 by both, KF and normal fibroblasts, was dependent on AKR1C3 as this reaction was attenuated in the presence of the AKR1C3 inhibitor, 2'-hydroxyflavanone, or in cells with decreased AKR1C3 expression. 15d-PGJ2, but not the other tested PGs, inhibited KF proliferation, attenuated KF-mediated collagen gel contraction and increased caspase-3 activation. In addition, treatment with 15d-PGJ2 activated P38-MAPK, induced reactive oxygen species and upregulated superoxide dismutase-1 (SOD-1). Finally, inhibition of P38-MAPK further augmented 15d-PGJ2-induced caspase-3 cleavage and attenuated its effect on SOD-1 transcription. This work suggests that localized dual inhibition of AKR1C3 and P38-MAPK may inhibit keloid progression. Inhibiting AKR1C3 activity may generate oxidative environment due to redirection of PGD2 metabolism towards 15d-PGJ2 while inhibition of P38-MAPK will sensitize keloid cells to ROS-induced apoptosis. PMID:26308156

  1. Aryl hydrocarbon receptor facilitates DNA strand breaks and 8-oxo-2'-deoxyguanosine formation by the aldo-keto reductase product benzo[a]pyrene-7,8-dione.

    PubMed

    Park, Jong-Heum; Mangal, Dipti; Frey, Alexander J; Harvey, Ronald G; Blair, Ian A; Penning, Trevor M

    2009-10-23

    Polycyclic aromatic hydrocarbon (PAH) o-quinones produced by aldo-keto reductases are ligands for the aryl hydrocarbon receptor (AhR) (Burczynski, M. E., and Penning, T. M. (2000) Cancer Res. 60, 908-915). They induce oxidative DNA lesions (reactive oxygen species-mediated DNA strand breaks and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo) formation) in human lung cells. We tested whether the AhR enhances PAH o-quinone-mediated oxidative DNA damage by translocating these ligands to the nucleus. Using the single cell gel electrophoresis (comet) assay to detect DNA strand breaks in murine hepatoma Hepa1c1c7 cells and its AhR- and aryl hydrocarbon receptor nuclear translocator-deficient variants, benzo[a]pyrene-7,8-dione (B[a]P-7,8-dione) produced fewer DNA strand breaks in AhR-deficient cells compared with aryl hydrocarbon receptor nuclear translocator-deficient and wild type Hepa1c1c7 cells. Decreased DNA strand breaks were also observed in human bronchoalveolar H358 cells in which the AhR was silenced by siRNA. The antioxidant alpha-tocopherol and the iron chelator/antioxidant desferal decreased the formation of B[a]P-7,8-dione-mediated DNA strand breaks indicating that they were reactive oxygen species-dependent. By coupling the comet assay to 8-oxoguanine glycosylase (hOGG1), which excises 8-oxo-Gua, strand breaks dependent upon this lesion were measured. hOGG1 treatment produced more DNA single strand breaks in B[a]P-7,8-dione-treated Hepa cells and H358 cells than in its absence. The levels of hOGG1-dependent DNA strand breaks mediated by B[a]P-7,8-dione were lower in AhR-deficient Hepa and AhR knockdown H358 cells. The AhR antagonist alpha-naphthoflavone also attenuated B[a]P-7,8-dione-mediated DNA strand breaks. The decrease in 8-oxo-dGuo levels in AhR-deficient Hepa cells and AhR knockdown H358 cells was validated by immunoaffinity capture stable isotope dilution ([(15)N(5)]8-oxo-dGuo) liquid chromatography-electrospray ionization/multiple reaction

  2. A Novel Aldo-Keto Reductase (AKR17A1) of Anabaena sp. PCC 7120 Degrades the Rice Field Herbicide Butachlor and Confers Tolerance to Abiotic Stresses in E. coli.

    PubMed

    Agrawal, Chhavi; Sen, Sonia; Yadav, Shivam; Rai, Shweta; Rai, Lal Chand

    2015-01-01

    Present study deals with the identification of a novel aldo/keto reductase, AKR17A1 from Anabaena sp. PCC7120 and adds on as 17th family of AKR superfamily drawn from a wide variety of organisms. AKR17A1 shares many characteristics of a typical AKR such as- (i) conferring tolerance to multiple stresses like heat, UV-B, and cadmium, (ii) excellent activity towards known AKR substrates (isatin and 2-nitrobenzaldehyde), and (iii) obligate dependence on NADPH as a cofactor for enzyme activity. The most novel attribute of AKR17A1, first reported in this study, is its capability to metabolize butachlor, a persistent rice field herbicide that adversely affects agro-ecosystem and non-target organisms. The AKR17A1 catalyzed- degradation of butachlor resulted into formation of 1,2-benzene dicarboxylic acid and 2,6 bis (1,1, dimethylethyl) 4,-methyl phenol as the major products confirmed by GC-MS analysis. PMID:26372161

  3. Synthesis and structure-activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3.

    PubMed

    Heinrich, Daniel M; Flanagan, Jack U; Jamieson, Stephen M F; Silva, Shevan; Rigoreau, Laurent J M; Trivier, Elisabeth; Raynham, Tony; Turnbull, Andrew P; Denny, William A

    2013-04-01

    High expression of the aldo-keto reductase enzyme AKR1C3 in the human prostate and breast has implicated it in the development and progression of leukemias and of prostate and breast cancers. Inhibitors are thus of interest as potential drugs. Most inhibitors of AKR1C3 are carboxylic acids, whose transport into cells is likely dominated by carrier-mediated processes. We describe here a series of (piperidinosulfonamidophenyl)pyrrolidin-2-ones as potent (<100 nM) and isoform-selective non-carboxylate inhibitors of AKR1C3. Structure-activity relationships identified the sulfonamide was critical, and a crystal structure showed the 2-pyrrolidinone does not interact directly with residues in the oxyanion hole. Variations in the position, co-planarity or electronic nature of the pyrrolidinone ring severely diminished activity, as did altering the size or polarity of the piperidino ring. There was a broad correlation between the enzyme potencies of the compounds and their effectiveness at inhibiting AKR1C3 activity in cells.

  4. A Novel Aldo-Keto Reductase (AKR17A1) of Anabaena sp. PCC 7120 Degrades the Rice Field Herbicide Butachlor and Confers Tolerance to Abiotic Stresses in E. coli

    PubMed Central

    Agrawal, Chhavi; Sen, Sonia; Yadav, Shivam; Rai, Shweta; Rai, Lal Chand

    2015-01-01

    Present study deals with the identification of a novel aldo/keto reductase, AKR17A1 from Anabaena sp. PCC7120 and adds on as 17th family of AKR superfamily drawn from a wide variety of organisms. AKR17A1 shares many characteristics of a typical AKR such as— (i) conferring tolerance to multiple stresses like heat, UV-B, and cadmium, (ii) excellent activity towards known AKR substrates (isatin and 2-nitrobenzaldehyde), and (iii) obligate dependence on NADPH as a cofactor for enzyme activity. The most novel attribute of AKR17A1, first reported in this study, is its capability to metabolize butachlor, a persistent rice field herbicide that adversely affects agro-ecosystem and non-target organisms. The AKR17A1 catalyzed- degradation of butachlor resulted into formation of 1,2-benzene dicarboxylic acid and 2,6 bis (1,1, dimethylethyl) 4,-methyl phenol as the major products confirmed by GC-MS analysis. PMID:26372161

  5. A Novel Aldo-Keto Reductase (AKR17A1) of Anabaena sp. PCC 7120 Degrades the Rice Field Herbicide Butachlor and Confers Tolerance to Abiotic Stresses in E. coli.

    PubMed

    Agrawal, Chhavi; Sen, Sonia; Yadav, Shivam; Rai, Shweta; Rai, Lal Chand

    2015-01-01

    Present study deals with the identification of a novel aldo/keto reductase, AKR17A1 from Anabaena sp. PCC7120 and adds on as 17th family of AKR superfamily drawn from a wide variety of organisms. AKR17A1 shares many characteristics of a typical AKR such as- (i) conferring tolerance to multiple stresses like heat, UV-B, and cadmium, (ii) excellent activity towards known AKR substrates (isatin and 2-nitrobenzaldehyde), and (iii) obligate dependence on NADPH as a cofactor for enzyme activity. The most novel attribute of AKR17A1, first reported in this study, is its capability to metabolize butachlor, a persistent rice field herbicide that adversely affects agro-ecosystem and non-target organisms. The AKR17A1 catalyzed- degradation of butachlor resulted into formation of 1,2-benzene dicarboxylic acid and 2,6 bis (1,1, dimethylethyl) 4,-methyl phenol as the major products confirmed by GC-MS analysis.

  6. Development of Potent and Selective Inhibitors of Aldo-Keto Reductase 1C3 (type 5 17β-Hydroxysteroid Dehydrogenase) Based on N-Phenyl-Aminobenzoates and Their Structure Activity Relationships

    PubMed Central

    Adeniji, Adegoke O.; Twenter, Barry M.; Byrns, Michael C.; Jin, Yi; Chen, Mo; Winkler, Jeffrey D.; Penning, Trevor M.

    2012-01-01

    Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castrate resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required since compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular are potent but non-selective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid as lead compound, five classes of structural analogs were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads towards new therapeutics for CRPC. PMID:22263837

  7. Identification of a determinant for strict NADP(H)-specificity and high sensitivity to mixed-type steroid inhibitor of rabbit aldo-keto reductase 1C33 by site-directed mutagenesis.

    PubMed

    Endo, Satoshi; Matsunaga, Toshiyuki; Ikari, Akira; El-Kabbani, Ossama; Hara, Akira; Kitade, Yukio

    2015-03-01

    In rabbit tissues, hydroxysteroid dehydrogenase belonging to the aldo-keto reductase (AKR) superfamily exists in six isoforms (AKRs: 1C5 and 1C29-1C33), sharing >73% amino acid sequence identity. AKR1C33 is strictly NADPH-specific, in contrast to dual NADPH/NADH specificity of the other isoforms. All coenzyme-binding residues of the structurally elucidated AKR1C5 are conserved in other isoforms, except that S217 (interacting with the pyrophosphate moiety) and T273 (interacting with the 2'-phosphate moiety) are replaced with F217 and N272, respectively, in AKR1C33. To explore the determinants for the NADPH specificity of AKR1C33, we prepared its F217S and N272T mutant enzymes. The mutation of F217S, but not N272T, converted AKR1C33 into a dually coenzyme-specific form that showed similar kcat values for NAD(P)H to those of AKR1C32. The reverse mutation (S217F) in dually coenzyme-specific AKR1C32 produced a strictly NADPH-specific form. The F217S mutation also abolished the activity towards 3-keto-5β-cholestanes that are substrates specific to AKR1C33, and markedly decreased the sensitivity to 4-pregnenes (such as deoxycorticosterone and medroxyprogesterone acetate) that were found to be potent mixed-type inhibitors of the wild-type enzyme. The results indicate the important role of F217 in the strict NADPH-dependency, as well as its involvement in the unique catalytic properties of AKR1C33.

  8. Aldo-keto reductase 1B10 promotes development of cisplatin resistance in gastrointestinal cancer cells through down-regulating peroxisome proliferator-activated receptor-γ-dependent mechanism.

    PubMed

    Matsunaga, Toshiyuki; Suzuki, Ayaka; Kezuka, Chihiro; Okumura, Naoko; Iguchi, Kazuhiro; Inoue, Ikuo; Soda, Midori; Endo, Satoshi; El-Kabbani, Ossama; Hara, Akira; Ikari, Akira

    2016-08-25

    Cisplatin (cis-diamminedichloroplatinum, CDDP) is one of the most effective chemotherapeutic drugs that are used for treatment of patients with gastrointestinal cancer cells, but its continuous administration often evokes the development of chemoresistance. In this study, we investigated alterations in antioxidant molecules and functions using a newly established CDDP-resistant variant of gastric cancer MKN45 cells, and found that aldo-keto reductase 1B10 (AKR1B10) is significantly up-regulated with acquisition of the CDDP resistance. In the nonresistant MKN45 cells, the sensitivity to cytotoxic effect of CDDP was decreased and increased by overexpression and silencing of AKR1B10, respectively. In addition, the AKR1B10 overexpression markedly suppressed accumulation and cytotoxicity of 4-hydroxy-2-nonenal that is produced during lipid peroxidation by CDDP treatment, suggesting that the enzyme acts as a crucial factor for facilitation of the CDDP resistance through inhibiting induction of oxidative stress by the drug. Transient exposure to CDDP and induction of the CDDP resistance decreased expression of peroxisome proliferator-activated receptor-γ (PPARγ) in MKN45 and colon cancer LoVo cells. Additionally, overexpression of PPARγ in the cells elevated the sensitivity to the CDDP toxicity, which was further augmented by concomitant treatment with a PPARγ ligand rosiglitazone. Intriguingly, overexpression of AKR1B10 in the cells resulted in a decrease in PPARγ expression, which was recovered by addition of an AKR1B10 inhibitor oleanolic acid, inferring that PPARγ is a downstream target of AKR1B10-dependent mechanism underlying the CDDP resistance. Combined treatment with the AKR1B10 inhibitor and PPARγ ligand elevated the CDDP sensitivity, which was almost the same level as that in the parental cells. These results suggest that combined treatment with the AKR1B10 inhibitor and PPARγ ligand is an effective adjuvant therapy for overcoming CDDP resistance of

  9. Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase.

    PubMed Central

    Ireland, L S; Harrison, D J; Neal, G E; Hayes, J D

    1998-01-01

    The masking of charged amino or carboxy groups by N-phthalidylation and O-phthalidylation has been used to improve the absorption of many drugs, including ampicillin and 5-fluorouracil. Following absorption of such prodrugs, the phthalidyl group is hydrolysed to release 2-carboxybenzaldehyde (2-CBA) and the pharmaceutically active compound; in humans, 2-CBA is further metabolized to 2-hydroxymethylbenzoic acid by reduction of the aldehyde group. In the present work, the enzyme responsible for the reduction of 2-CBA in humans is identified as a homologue of rat aflatoxin B1-aldehyde reductase (rAFAR). This novel human aldo-keto reductase (AKR) has been cloned from a liver cDNA library, and together with the rat protein, establishes the AKR7 family of the AKR superfamily. Unlike its rat homologue, human AFAR (hAFAR) appears to be constitutively expressed in human liver, and is widely expressed in extrahepatic tissues. The deduced human and rat protein sequences share 78% identity and 87% similarity. Although the two AKR7 proteins are predicted to possess distinct secondary structural features which distinguish them from the prototypic AKR1 family of AKRs, the catalytic- and NADPH-binding residues appear to be conserved in both families. Certain of the predicted structural features of the AKR7 family members are shared with the AKR6 beta-subunits of voltage-gated K+-channels. In addition to reducing the dialdehydic form of aflatoxin B1-8,9-dihydrodiol, hAFAR shows high affinity for the gamma-aminobutyric acid metabolite succinic semialdehyde (SSA) which is structurally related to 2-CBA, suggesting that hAFAR could function as both a SSA reductase and a 2-CBA reductase in vivo. This hypothesis is supported in part by the finding that the major peak of 2-CBA reductase activity in human liver co-purifies with hAFAR protein. PMID:9576847

  10. A Novel Aldo-Keto Reductase, HdRed, from the Pacific Abalone Haliotis discus hannai, Which Reduces Alginate-derived 4-Deoxy-L-erythro-5-hexoseulose Uronic Acid to 2-Keto-3-deoxy-D-gluconate.

    PubMed

    Mochizuki, Shogo; Nishiyama, Ryuji; Inoue, Akira; Ojima, Takao

    2015-12-25

    Abalone feeds on brown seaweeds and digests seaweeds' alginate with alginate lyases (EC 4.2.2.3). However, it has been unclear whether the end product of alginate lyases (i.e. unsaturated monouronate-derived 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEH)) is assimilated by abalone itself, because DEH cannot be metabolized via the Embden-Meyerhof pathway of animals. Under these circumstances, we recently noticed the occurrence of an NADPH-dependent reductase, which reduced DEH to 2-keto-3-deoxy-D-gluconate, in hepatopancreas extract of the pacific abalone Haliotis discus hannai. In the present study, we characterized this enzyme to some extent. The DEH reductase, named HdRed in the present study, could be purified from the acetone-dried powder of hepatopancreas by ammonium sulfate fractionation followed by conventional column chromatographies. HdRed showed a single band of ∼ 40 kDa on SDS-PAGE and reduced DEH to 2-keto-3-deoxy-D-gluconate with an optimal temperature and pH at around 50 °C and 7.0, respectively. HdRed exhibited no appreciable activity toward 28 authentic compounds, including aldehyde, aldose, ketose, α-keto-acid, uronic acid, deoxy sugar, sugar alcohol, carboxylic acid, ketone, and ester. The amino acid sequence of 371 residues of HdRed deduced from the cDNA showed 18-60% identities to those of aldo-keto reductase (AKR) superfamily enzymes, such as human aldose reductase, halophilic bacterium reductase, and sea hare norsolorinic acid (a polyketide derivative) reductase-like protein. Catalytic residues and cofactor binding residues known in AKR superfamily enzymes were fairly well conserved in HdRed. Phylogenetic analysis for HdRed and AKR superfamily enzymes indicated that HdRed is an AKR belonging to a novel family. PMID:26555267

  11. A Novel Aldo-Keto Reductase, HdRed, from the Pacific Abalone Haliotis discus hannai, Which Reduces Alginate-derived 4-Deoxy-L-erythro-5-hexoseulose Uronic Acid to 2-Keto-3-deoxy-D-gluconate.

    PubMed

    Mochizuki, Shogo; Nishiyama, Ryuji; Inoue, Akira; Ojima, Takao

    2015-12-25

    Abalone feeds on brown seaweeds and digests seaweeds' alginate with alginate lyases (EC 4.2.2.3). However, it has been unclear whether the end product of alginate lyases (i.e. unsaturated monouronate-derived 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEH)) is assimilated by abalone itself, because DEH cannot be metabolized via the Embden-Meyerhof pathway of animals. Under these circumstances, we recently noticed the occurrence of an NADPH-dependent reductase, which reduced DEH to 2-keto-3-deoxy-D-gluconate, in hepatopancreas extract of the pacific abalone Haliotis discus hannai. In the present study, we characterized this enzyme to some extent. The DEH reductase, named HdRed in the present study, could be purified from the acetone-dried powder of hepatopancreas by ammonium sulfate fractionation followed by conventional column chromatographies. HdRed showed a single band of ∼ 40 kDa on SDS-PAGE and reduced DEH to 2-keto-3-deoxy-D-gluconate with an optimal temperature and pH at around 50 °C and 7.0, respectively. HdRed exhibited no appreciable activity toward 28 authentic compounds, including aldehyde, aldose, ketose, α-keto-acid, uronic acid, deoxy sugar, sugar alcohol, carboxylic acid, ketone, and ester. The amino acid sequence of 371 residues of HdRed deduced from the cDNA showed 18-60% identities to those of aldo-keto reductase (AKR) superfamily enzymes, such as human aldose reductase, halophilic bacterium reductase, and sea hare norsolorinic acid (a polyketide derivative) reductase-like protein. Catalytic residues and cofactor binding residues known in AKR superfamily enzymes were fairly well conserved in HdRed. Phylogenetic analysis for HdRed and AKR superfamily enzymes indicated that HdRed is an AKR belonging to a novel family.

  12. Catalytic mechanism of the primary human prostaglandin F2α synthase, aldo-keto reductase 1B1--prostaglandin D2 synthase activity in the absence of NADP(H).

    PubMed

    Nagata, Nanae; Kusakari, Yukiko; Fukunishi, Yoshifumi; Inoue, Tsuyoshi; Urade, Yoshihiro

    2011-04-01

    Aldo-keto reductase 1B1 and 1B3 (AKR1B1 and AKR1B3) are the primary human and mouse prostaglandin F(2α) (PGF(2α)) synthases, respectively, which catalyze the NADPH-dependent reduction of PGH(2), a common intermediate of various prostanoids, to form PGF(2α). In this study, we found that AKR1B1 and AKR1B3, but not AKR1B7 and AKR1C3, also catalyzed the isomerization of PGH(2) to PGD(2) in the absence of NADPH or NADP(+). Both PGD(2) and PGF(2α) synthase activities of AKR1B1 and AKR1B3 completely disappeared in the presence of NADP(+) or after heat treatment of these enzymes at 100 °C for 5 min. The K(m), V(max), pK and optimum pH values of the PGD(2) synthase activities of AKR1B1 and AKR1B3 were 23 and 18 μM, 151 and 57 nmol·min(-1)·(mg protein)(-1), 7.9 and 7.6, and pH 8.5 for both AKRs, respectively, and those of PGF(2α) synthase activity were 29 and 33 μM, 169 and 240 nmol·min(-1)·(mg protein)(-1), 6.2 and 5.4, and pH 5.5 and pH 5.0, respectively, in the presence of 0.5 mm NADPH. Site-directed mutagenesis of the catalytic tetrad of AKR1B1, composed of Tyr, Lys, His and Asp, revealed that the triad of Asp43, Lys77 and His110, but not Tyr48, acts as a proton donor in most AKR activities, and is crucial for PGD(2) and PGF(2α) synthase activities. These results, together with molecular docking simulation of PGH(2) to the crystallographic structure of AKR1B1, indicate that His110 acts as a base in concert with Asp43 and Lys77 and as an acid to generate PGD(2) and PGF(2α) in the absence of NADPH or NADP(+) and in the presence of NADPH, respectively.

  13. Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system confirms the prostaglandin F2α synthase activity of aldo-ketoreductase 1B1.

    PubMed

    Lacroix Pépin, Nicolas; Chapdelaine, Pierre; Rodriguez, Yoima; Tremblay, Jacques-P; Fortier, Michel A

    2014-07-01

    Prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2α. Relatively little is known about the biosynthetic pathways leading to the formation of PGF2α. We have described the role of aldo-ketoreductase (AKR)1B1 in increased PGF2α production by human endometrial cells following stimulation with interleukin-1β (IL-1β). However, alternate PGF synthases are expressed concurrently in endometrial cells. A definite proof of the role of AKR1B1 would require gene knockout; unfortunately, this gene has no direct equivalent in the mouse. Recently, an efficient genome-editing technology using RNA-guided DNase Cas9 and the clustered regularly interspaced short palindromic repeats (CRISPR) system has been developed. We have adapted this approach to knockout AKR1B1 gene expression in human endometrial cell lines. One clone (16-2) of stromal origin generated by the CRISPR/Cas9 system exhibited a complete loss of AKR1B1 protein and mRNA expression, whereas other clones presented with partial edition. The present report focuses on the characterization of clone 16-2 exhibiting deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lost their ability to produce PGF2α but maintained their original stromal cell (human endometrial stromal cells-2) phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintained their ability to increase PGE2 production in response to IL-1β. In summary, we demonstrate that the new genome editing CRISPR/Cas9 system can be used in human cells to generate stable knockout cell line models. Our results suggest that genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells. Our results also confirm that AKR1B1 is involved in the synthesis of PGF2α.

  14. Sulindac inhibits pancreatic carcinogenesis in LSL-KrasG12D-LSL-Trp53R172H-Pdx-1-Cre mice via suppressing aldo-keto reductase family 1B10 (AKR1B10).

    PubMed

    Li, Haonan; Yang, Allison L; Chung, Yeon Tae; Zhang, Wanying; Liao, Jie; Yang, Guang-Yu

    2013-09-01

    Sulindac has been identified as a competitive inhibitor of aldo-keto reductase 1B10 (AKR1B10), an enzyme that plays a key role in carcinogenesis. AKR1B10 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and exhibits lipid substrate specificity, especially for farnesyl and geranylgeranyl. There have been no studies though showing that the inhibition of PDAC by sulindac is via inhibition of AKR1B10, particularly the metabolism of farnesyl/geranylgeranyl and Kras protein prenylation. To determine the chemopreventive effects of sulindac on pancreatic carcinogenesis, 5-week-old LSL-Kras(G12D)-LSL-Trp53(R172H)-Pdx-1-Cre mice (Pan(kras/p53) mice) were fed an AIN93M diet with or without 200 p.p.m. sulindac (n = 20/group). Kaplan-Meier survival analysis showed that average animal survival in Pan(kras/p53) mice was 143.7 ± 8.8 days, and average survival with sulindac was increased to 168.0 ± 8.8 days (P < 0.005). Histopathological analyses revealed that 90% of mice developed PDAC, 10% with metastasis to the liver and lymph nodes. With sulindac, the incidence of PDAC was reduced to 56% (P < 0.01) and only one mouse had lymph node metastasis. Immunochemical analysis showed that sulindac significantly decreased Ki-67-labeled cell proliferation and markedly reduced the expression of phosphorylated extracellular signal-regulated kinases 1 and 2 (ERK1/2), c-Raf and mitogen-activated protein kinase kinase 1 and 2. In in vitro experiments with PDAC cells from Pan(kras/p53) mice, sulindac exhibited dose-dependent inhibition of AKR1B10 activity. By silencing AKR1B10 expression through small interfering RNA or by sulindac treatment, these in vitro models showed a reduction in Kras and human DNA-J homolog 2 protein prenylation, and downregulation of phosphorylated C-raf, ERK1/2 and MEK1/2 expression. Our results demonstrate that sulindac inhibits pancreatic carcinogenesis by the inhibition of Kras protein prenylation by targeting AKR1B10.

  15. List of Participants

    NASA Astrophysics Data System (ADS)

    2014-07-01

    Alba Paolo (Università di Torino) Becattini Francesco (Università di Firenze) Bombaci Ignazio (Università di Pisa) Bonaccorso Angela (INFN Pisa) Colonna Maria (INFN-LNS Catania) Coraggio Luigi (INFN Napoli) Covello Aldo (Università di Napoli) Di Toro Massimo (Università di Catania) De Angelis Giacomo (INFN-LNL Legnaro) Gargano Angela (INFN Napoli) Gattobigio Mario (INLN, Université de Nice-Sophia Antipolis, CNRS, France) Gensini Paolo (INFN Lecce) Giannini Mauro (Università di Genova) Girlanda Luca (Università del Salento) Giusti Carlotta (Università di Pavia) Greco Vincenzo (Università di Catania) Grossi Eduardo (Università di Firenze) Itaco Nunzio (Università di Napoli) Kievsky Alejandro (INFN Pisa) Lanza Edoardo (INFN Catania) Lavagno Andrea (Politecnico di Torino) Logoteta Domenico (Universidade de Coimbra, Coimbra, Portugal) Lo Iudice Nicola (Università di Napoli) Lombardo Maria Paola (INFN-LNF Frascati) Lo Meo Sergio (ENEA Bologna) Mannarelli Massimo (INFN-LNGS Assergi) Marcucci Laura Elisa (Università di Pisa) Matera Francesco (Università di Firenze) Orlandini Giuseppina (Università di Trento) Pacati Franco (Università di Pavia) Pederiva Francesco (Università di Trento) Pirrone Sara (INFN Catania) Puglisi Armando (Università di Catania) Radici Marco (INFN Pavia) Rinaldi Matteo (Università di Perugia) Roggero Alessandro (Università di Trento) Rolando Valentina (Università di Ferrara) Rosati Sergio (Università di Pisa) Ruggieri Marco (Università di Catania) Salmè Gianni (INFN Roma) Santopinto Elena (INFN Genova) Scopetta Sergio (Università di Perugia) Taiuti Mauro (Università di Genova) Vigezzi Enrico (INFN Milano) Viviani Michele (INFN Pisa) Vorabbi Matteo (Università di Pavia)

  16. Fine tuning of coenzyme specificity in family 2 aldo-keto reductases revealed by crystal structures of the Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD + and NADP +

    SciTech Connect

    Leitgeb, Stefan; Petschacher, Barbara; Wilson, David K.; Nidetzky, Bernd

    2005-01-11

    Aldo-keto reductases of family 2 employ single site replacement Lys → Arg to switch their cosubstrate preference from NADPH to NADH. X-ray crystal structures of Lys-274 → Arg mutant of Candida tenuis xylose reductase (AKR2B5) bound to NAD+ and NADP+ were determined at a resolution of 2.4 and 2.3 Å, respectively. Due to steric conflicts in the NADP+-bound form, the arginine side chain must rotate away from the position of the original lysine side chain, thereby disrupting a network of direct and water-mediated interactions between Glu-227, Lys-274 and the cofactor 2'-phosphate and 3'-hydroxy groups. Because anchoring contacts of its Glu-227 are lost, the coenzyme-enfolding loop that becomes ordered upon binding of NAD(P)+ in the wild-type remains partly disordered in the NADP+-bound mutant. The results delineate a catalytic reaction profile for the mutant in comparison to wild-type.

  17. Long Term Data Preservation for CDF at INFN-CNAF

    NASA Astrophysics Data System (ADS)

    Amerio, S.; Chiarelli, L.; dell'Agnello, L.; De Girolamo, D.; Gregori, D.; Pezzi, M.; Prosperini, A.; Ricci, P.; Rosso, F.; Zani, S.

    2014-06-01

    Long-term preservation of experimental data (intended as both raw and derived formats) is one of the emerging requirements coming from scientific collaborations. Within the High Energy Physics community the Data Preservation in High Energy Physics (DPHEP) group coordinates this effort. CNAF is not only one of the Tier-1s for the LHC experiments, it is also a computing center providing computing and storage resources to many other HEP and non-HEP scientific collaborations, including the CDF experiment. After the end of data taking in 2011, CDF is now facing the challenge to both preserve the large amount of data produced during several years of data taking and to retain the ability to access and reuse it in the future. CNAF is heavily involved in the CDF Data Preservation activities, in collaboration with the Fermilab National Laboratory (FNAL) computing sector. At the moment about 4 PB of data (raw data and analysis-level ntuples) are starting to be copied from FNAL to the CNAF tape library and the framework to subsequently access the data is being set up. In parallel to the data access system, a data analysis framework is being developed which allows to run the complete CDF analysis chain in the long term future, from raw data reprocessing to analysis-level ntuple production. In this contribution we illustrate the technical solutions we put in place to address the issues encountered as we proceeded in this activity.

  18. Construction of superconducting RFQs at INFN-LNL

    NASA Astrophysics Data System (ADS)

    Bisoffi, G.; Andreev, V.; Bissiato, E.; Comunian, M.; Chiurlotto, F.; Corradin, E.; Lollo, M.; Lombardi, A.; Pisent, A.; Porcellato, A. M.; Shirai, T.; Tovo, E.; Tovo, R.

    1999-04-01

    The tests on the stainless steel prototype for one of the two superconducting RFQs (SRFQs) for PIAVE (SRFQ2), the being built heavy ion injector for the Legnaro booster, were completed in summer 1998, while the construction of the first niobium resonator started in February 1998 and is expected to be completed by April 1999. The structure, resonating at 80 MHz, is 0.8 m long and 0.76 m in diameter. All technological aspects connected with the construction of the SRFQs, and the corresponding tests on the stainless steel model, are reviewed: development of the parts, assembly sequence, electron beam welding (EBW) steps, rough and fine adjustment of the resonant frequency, bead-pull measurements, characterization of the mechanical vibration modes, frequency change due to cooling down and chemical etching tests. The updated development of SRFQ1 is briefly reviewed.

  19. List of Participants

    NASA Astrophysics Data System (ADS)

    Bombaci, I.; Covello, A.; Marcucci, L. E.; Rosati, S.

    2009-07-01

    Armani Paolo (Università di Trento) Benhar Omar (INFN Roma) Bombaci Ignazio (Università di Pisa) Bonanno Luca (Università di Ferrara) Catara Francesco (Università di Catania) Cò Giampaolo (Università di Lecce) Colonna Maria (Laboratori Nazionali del Sud, INFN Catania) Colonna Nicola (INFN Bari) Conti Francesco (Università di Pavia) Coraggio Luigi (INFN Napoli) Covello Aldo (Università di Napoli) Cristoforetti Marco (Technische Universität München, Germania) Cuofano Carmine (Università di Ferrara) Di Toro Massimo (Università di Catania) Drago Alessandro (Università di Ferrara) Faccioli Pietro (Università di Trento) Farina Nicola (INFN Roma) Finelli Paolo (Università di Bologna) Fiorentini Giovanni (Università di Ferrara) Fortunato Lorenzo (Università di Padova) Gambacurta Danilo (Università di Catania) Gandolfi Stefano (Università di Trento) Gargano Angela (INFN Napoli) Giannini Mauro (Università di Genova) Girlanda Luca (INFN Pisa) Giusti Carlotta (INFN Pavia) Illarionov Alexei (SISSA Trieste) Itaco Nunzio (Università di Napoli) Kievsky Alejandro (INFN Pisa) Lanza Edoardo (INFN Catania) Leidemann Winfried (Università di Trento) Lenzi Silvia (Università di Padova) Lipparini Enrico (Università di Trento) Lissia Marcello (Università di Cagliari) Lo Iudice Nicola (Università di Napoli) Maieron Chiara (Università di Lecce) Marcucci Laura Elisa (Università di Pisa) Matera Francesco (Università di Firenze) Millo Raffaele (Università di Trento) Orlandini Giuseppina (Università di Trento) Pacati Franco (Università di Pavia) Pastore Alessandro (Univeristy of Jyväskylä, Finlandia) Pederiva Francesco (Università di Trento) Pisent Gualtiero (Università di Padova) Prete Gianfranco (INFN Laboratori Nazionali di Legnaro) Quarati Piero (Politecnico di Torino) Rosati Sergio (Università di Pisa) Salmè Giovanni (INFN Roma) Santopinto Elena (INFN Genova) Traini Marco (Università di Trento) Vigezzi Enrico (INFN Milano) Vitturi Andrea (Universit

  20. Aldo-Keto Reductases 1B in Endocrinology and Metabolism

    PubMed Central

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers. PMID:22876234

  1. Aldo-Keto Reductases 1B in Endocrinology and Metabolism.

    PubMed

    Pastel, Emilie; Pointud, Jean-Christophe; Volat, Fanny; Martinez, Antoine; Lefrançois-Martinez, Anne-Marie

    2012-01-01

    The aldose reductase (AR; human AKR1B1/mouse Akr1b3) has been the focus of many research because of its role in diabetic complications. The starting point of these alterations is the massive entry of glucose in polyol pathway where it is converted into sorbitol by this enzyme. However, the issue of AR function in non-diabetic condition remains unresolved. AR-like enzymes (AKR1B10, Akr1b7, and Akr1b8) are highly related isoforms often co-expressed with bona fide AR, making functional analysis of one or the other isoform a challenging task. AKR1B/Akr1b members share at least 65% protein identity and the general ability to reduce many redundant substrates such as aldehydes provided from lipid peroxidation, steroids and their by-products, and xenobiotics in vitro. Based on these properties, AKR1B/Akr1b are generally considered as detoxifying enzymes. Considering that divergences should be more informative than similarities to help understanding their physiological functions, we chose to review specific hallmarks of each human/mouse isoforms by focusing on tissue distribution and specific mechanisms of gene regulation. Indeed, although the AR shows ubiquitous expression, AR-like proteins exhibit tissue-specific patterns of expression. We focused on three organs where certain isoforms are enriched, the adrenal gland, enterohepatic, and adipose tissues and tried to connect recent enzymatic and regulation data with endocrine and metabolic functions of these organs. We presented recent mouse models showing unsuspected physiological functions in the regulation of glucido-lipidic metabolism and adipose tissue homeostasis. Beyond the widely accepted idea that AKR1B/Akr1b are detoxification enzymes, these recent reports provide growing evidences that they are able to modify or generate signal molecules. This conceptually shifts this class of enzymes from unenviable status of scavenger to upper class of messengers.

  2. Life as a Sober Citizen: Aldo Leopold's Wildlife Ecology 118

    ERIC Educational Resources Information Center

    Theiss, Nancy Stearns

    2009-01-01

    This historic case study addressed the issue of the lack of citizen action toward environmentally responsible behavior. Although there have been studies regarding components of environmental responsible behavior [ERB], there has been little focus on historic models of exemplary figures of ERB. This study examined one of the first conservation…

  3. List of Participants

    NASA Astrophysics Data System (ADS)

    2011-08-01

    Abigail Alvarez OlarteCINVESTAV Alba Leticia Carrillo MonteverdeDCI-UG Alberto CarramiñanaINAOE Aldo MorselliFERMI Alejandro CastillaDCI-UG Alejandro IbarraTechnical University of Munich Alma D Rojas PachecoFCFM-BUAP Alma Xochitl Gonzalez MoralesInstituto de Ciencias Nucleares, UNAM Andrew Walcott BeckwithAmerican Institute of Beam Energy Physics Ariadna Montiel ArenasDepartamento de Física, CINVESTAV Arnulfo ZepedaCinvestav Arturo Alvarez CruzInstituto de Fisica, UNAM Axel de la MacorraUNAM, IAC Azar MustafayevUniversity of Minnesota Benjamin JaramilloDCI-UG Vincent BertinCPPM-Marseille Carlos Alberto Vaquera-AraujoDCI-UG Carlos MuñozMadrid Autonoma U. & Madrid, IFT Carmine PagliaroneINFN, FNAL Carolina Lujan PeschardDCI-UG Christiane Frigerio MartinsUniversidade Federal do ABC-São Paulo Csaba BalazsMonash University David DelepineDCI-UG David G CerdenoUniversidad Autonoma de Madrid & Instituto de Fisica Teorica Debasish MajumdarSaha Institute of Nuclear Physics, Kolkata, India Dibyendu PanigrahiKandi Raj College, Kandi, Murshidabad, INDIA-742137 Dupret Alberto Santana BejaranoUniversidad de Sonora Departamento de Investigacion en Fisica Ernest MaRiverside U.C. Esteban Alejandro Reyes Pírez MontañezInstituto de Física, UNAM Federico Ortiz TrejoINSTITUTO DE ASTRONOMÍA - UNAM Francisco José de Anda NavarroUniversidad de Guadalajara González Alvarez Francisco JavierCINVESTAV-Depto. Física Gustavo Medina TancoICN-UNAM Hernando Efrain Caicedo OrtizInstituto Politecnico Nacional - IPN J D VergadosCERN & Ioannina U. James R BoyceJefferson Lab Jason SteffenFERMILAB Javier Montaño DomínguezDCI-UG Jeevan SolankiMandsaur Institue of Technology MP India Joe SatoSaitama University Jorge Luis Navarro EstradaUNAM-ICN and Universidad del Atlantico (B/quilla-Col.) Jose A R CembranosUniversity of Minnesota José DíazIFIC Jose Didino Garcia AguilarDepto. de Fisica. Cinvestav Keith OliveUniversity of Minnesota Konstantia BalasiUniversity of Ioannina, Greece Lilian Prado

  4. The INFN-FBK pixel R&D program for HL-LHC

    NASA Astrophysics Data System (ADS)

    Meschini, M.; Dalla Betta, G. F.; Boscardin, M.; Calderini, G.; Darbo, G.; Giacomini, G.; Messineo, A.; Ronchin, S.

    2016-09-01

    We report on the ATLAS and CMS joint research activity, which is aiming at the development of new, thin silicon pixel detectors for the Large Hadron Collider Phase-2 detector upgrades. This R&D is performed under special agreement between Istituto Nazionale di Fisica Nucleare and FBK foundation (Trento, Italy). New generations of 3D and planar pixel sensors with active edges are being developed in the R&D project, and will be fabricated at FBK. A first planar pixel batch, which was produced by the end of year 2014, will be described in this paper. First clean room measurement results on planar sensors obtained before and after neutron irradiation will be presented.

  5. Dosimetric and clinical experience in eye proton treatment at INFN-LNS

    SciTech Connect

    Cirrone, G. A. P.; Cuttone, G.; Di Rosa, F.; Lojacono, P.; Mongelli, V.; Patti, I. V.; Pittera, S.; Russo, G.; Valastro, L. M.; Lo Nigro, S.; Ott, J.; Reibaldi, A.; Privitera, G.; Raffaele, L.; Salamone, V.; Spatola, C.; Sabini, M. G.

    2009-05-04

    After six years of activity 155 patients have been treated inside the CATANA (Centro di AdroTerapia ed Applicazioni Nucleari Avanzate) facility. CATANA is the first and unique proton therapy facility in which the 62 MeV proton beams, accelerated by a Superconducting Cyclotron, are used for the radio-therapeutic treatments of choroidal and iris melanomas. Inside CATANA new absolute and relative dosimetric techniques have been developed in order to achieve the best results in terms of treatment precision and dose release accuracy. The follow-up results for 42 patients demonstrated the efficacy of high energy protons in the radiotherapeutic field and encouraged us in our activity in the battle against cancer.

  6. Preliminary measurements on the new TOF system installed at the AMS beamline of INFN-LABEC

    NASA Astrophysics Data System (ADS)

    Palla, L.; Castelli, L.; Czelusniak, C.; Fedi, M. E.; Giuntini, L.; Liccioli, L.; Mandò, P. A.; Martini, M.; Mazzinghi, A.; Ruberto, C.; Schiavulli, L.; Sibilia, E.; Taccetti, F.

    2015-10-01

    A high resolution time of flight (TOF) system has been developed at LABEC, the 3 MV Tandem accelerator laboratory in Florence, in order to improve the sensitivity of AMS measurements on carbon samples with ultra-low concentration and also to measure other isotopes, such as 129I. The system can be employed to detect and identify residual interfering particles originated from the break-up of molecular isobars. The set-up has been specifically designed for low energy heavy ions: it consists of two identical time pick-off stations, each made up of a thin conductive foil and a Micro-Channel Plate (MCP) multiplier. The beamline is also equipped with a silicon detector, installed downstream the stop TOF station. In this paper the design of the new system and the implemented readout electronics are presented. The tests performed on the single time pick-off station are reported: they show that the maximum contribution to the timing resolution given by both the intrinsic MCP resolution and the electronics is ⩽500 ps (FWHM). For these tests, single particle pulsed beams of 2-5 MeV protons and 10 MeV 12C3+ ions, to simulate typical AMS conditions, were used. The preliminary TOF and TOF-E (TOF-energy) measurements performed with carbon beams after the installation of the new system on the AMS beam line are also discussed. These measurements were performed using the foil-MCP as the start stage and a silicon detector as the stop stage. The spectra acquired with carbon ions suggest the presence of a small residual background from neighboring masses reaching the end of the beamline with the same energy as the rare isotope.

  7. Status and perspectives of the EXCYT facility at INFN-LNS

    NASA Astrophysics Data System (ADS)

    Cuttone, G.; Calabretta, L.; Celona, L.; Chines, F.; Cosentino, L.; Finocchiaro, P.; Pappalardo, A.; Re, M.; Rifuggiato, D.; Rovelli, A.

    2008-10-01

    The aim of the EXCYT (EXotics with CYclotron and Tandem) facility is the production and acceleration of radioactive ion beams (RIBs). A primary beam provided by the K-800 superconducting cyclotron will produce, in a target-ion source complex (TIS), the required nuclear species which can be used for low energy experiments (up to 300 keV) or at higher energy by post-accelerating them with the 15 MV tandem. The nuclear experiments programme started in July 2006 with the experiments BIGBANG and RCS using the post-accelerated 8Li ions. Since then 8Li, 9Li and 21Na beams have been already produced and in the near future production of oxygen, fluorine and chlorine beams have been planned, according to the experimental proposals, with beam intensities ranging between 104 to 106 pps and at the typical energies of our tandem.

  8. PREFACE: XIV Conference on Theoretical Nuclear Physics in Italy

    NASA Astrophysics Data System (ADS)

    Bombaci, I.; Covello, A.; Marcucci, L. E.; Rosati, S.

    2014-07-01

    This volume contains the invited and contributed papers presented at the 14th Conference on Theoretical Nuclear Physics in Italy held in Cortona, Italy, from 29-31 October, 2013. The meeting was held at the Palazzone, an elegant Renaissance Villa, commissioned by the Cardinal Silvio Passerini (1469-1529), Bishop of Cortona, and presently owned by the Scuola Normale Superiore di Pisa. The aim of this biennial Conference is to bring together Italian theorists working in various fields of nuclear physics to discuss their latest results and confront their points of view in a lively and informal way. This offers the opportunity to stimulate new ideas and promote collaborations between different research groups. The Conference was attended by 46 participants, coming from 13 Italian Universities and 11 Laboratories and Sezioni of the Istituto Nazionale di Fisica Nucleare - INFN. The program of the conference, prepared by the Organizing Committee (Ignazio Bombaci, Aldo Covello, Laura Elisa Marcucci and Sergio Rosati) focused on the following main topics: Few-Nucleon Systems Nuclear Structure Nuclear Matter and Nuclear Dynamics Relativistic Heavy Ion Collisions and Quark-Gluon Plasma Nuclear Astrophysics Nuclear Physics with Electroweak Probes Structure of Hadrons and Hadronic Matter. In the last session of the Conference there were two invited review talks related to experimental activities of great current interest. Giacomo De Angelis from the Laboratori Nazionali di Legnaro spoke about the INFN SPES radioactive ion beam project. Sara Pirrone, INFN Sezione di Catania, gave a talk on the symmetry energy and isospin physics with the CHIMERA detector. Finally, Mauro Taiuti (Università di Genova), National Coordinator of the INFN-CSN3 (Nuclear Physics Experiments), reported on the present status and future challenges of experimental nuclear physics in Italy. We gratefully acknowledge the financial support of INFN who helped make the conference possible. I Bombaci, A Covello

  9. The "I-Thou" Relationship, Place-Based Education, and Aldo Leopold

    ERIC Educational Resources Information Center

    Knapp, Clifford E.

    2005-01-01

    This article describes a new educational field labeled "place-based education" and relates it to experiential learning. This term has appeared in the educational literature over the last 10 years and illustrates a concern for providing participants with quality experiences in local settings. After defining and describing the term, one aspect of…

  10. Perspectives from the Aldo Leopold Wilderness Research Institute: Amphibians and wilderness

    USGS Publications Warehouse

    Corn, Paul Stephen

    2001-01-01

    The decline of amphibian species has emerged as a major global conservation issue in the last decade. Last year, the Department of the Interior (DOI) initiated a major national initiative to detect trends in amphibian populations and research the causes of declines. The program, conducted principally by the U.S. Geological Survey (USGS), emphasizes lands managed by DOI, but collaboration with the Forest Service is encouraged to increase the scope of inference about population trends. Although amphibians are not usually the first group of animals that comes to mind when one thinks of wilderness, conservation of amphibian populations is clearly a wilderness issue.

  11. Oxidation of PAH trans-Dihydrodiols by Human Aldo-Keto Reductase AKR1B10

    PubMed Central

    Quinn, Amy M.; Harvey, Ronald G.; Penning, Trevor M.

    2009-01-01

    AKR1B10 has been identified as a potential biomarker for human non-small cell lung carcinoma and as a tobacco exposure and response gene. AKR1B10 functions as an efficient retinal reductase in vitro, and may regulate retinoic acid homeostasis. However, the possibility that this enzyme is able to activate polycyclic aromatic hydrocarbon (PAH) trans-dihydrodiols to form reactive and redox-active o-quinones has not been investigated to date. AKR1B10 was found to oxidize a wide range of PAH trans-dihydrodiol substrates in vitro to yield PAH o-quinones. Reactions of AKR1B10 proceeded with improper stereochemistry, since it was specific for the minor (+)-benzo[a]pyrene-7S,8S-dihydrodiol diastereomer formed in vivo. However, AKR1B10 displayed reasonable activity in the oxidation of both the (−)-R,R and (+)-S,S stereoisomers of benzo[g]chrysene-11,12-dihydrodiol and oxidized the potentially relevant, albeit minor, (+)-benz[a]anthracene-3S,4S-dihydrodiol metabolite. We find that AKR1B10 is therefore likely to play a contributing role in the activation of PAH trans-dihydrodiols in human lung. AKR1B10 retinal reductase activity was confirmed in vitro and found to be 5- to 150-fold greater than the oxidation of PAH trans-dihydrodiols examined. AKR1B10 was highly expressed at the mRNA and protein levels in human lung adenocarcinoma A549 cells, and robust retinal reductase activity was measured in lysates of these cells. The much greater catalytic efficiency of retinal reduction compared to PAH trans-dihydrodiol metabolism suggests AKR1B10 may play a greater role in lung carcinogenesis through dysregulation of retinoic acid homeostasis than through oxidation of PAH trans-dihydrodiols. PMID:18788756

  12. First beams from the new electron cyclotron resonance source LEGIS (LEGnaro ecrIS) at INFN-LNL

    SciTech Connect

    Galata, A.; Sattin, M.; Scarpa, F.; Facco, A.; Kulevoy, T.

    2010-02-15

    From April 2008 the PIAVE injector for the ALPI booster was involved in the upgrade of the high voltage platform housing an electron cyclotron resonance (ECR) source. A 14.5 GHz SUPERNANOGAN type ECR replaced the existing source ALICE; at the same time, the whole platform beam line was redesigned and beam shaping and diagnostic system were installed. The source and the platform were ready to be put into operation in January 2009. PIAVE's commissioning was started from late March and completed in May 2009 using an argon beam. A description of the upgrade will be given in the following; beam quality leading to an improved transmission through the injector will be shown. Results on first gaseous and metallic beams produced will also be given.

  13. First beams from the new electron cyclotron resonance source LEGIS (LEGnaro ecrIS) at INFN-LNL.

    PubMed

    Galatà, A; Kulevoy, T; Sattin, M; Scarpa, F; Facco, A

    2010-02-01

    From April 2008 the PIAVE injector for the ALPI booster was involved in the upgrade of the high voltage platform housing an electron cyclotron resonance (ECR) source. A 14.5 GHz SUPERNANOGAN type ECR replaced the existing source ALICE; at the same time, the whole platform beam line was redesigned and beam shaping and diagnostic system were installed. The source and the platform were ready to be put into operation in January 2009. PIAVE's commissioning was started from late March and completed in May 2009 using an argon beam. A description of the upgrade will be given in the following; beam quality leading to an improved transmission through the injector will be shown. Results on first gaseous and metallic beams produced will also be given.

  14. Correlation between groundwater flow and deformation in the fractured carbonate Gran Sasso aquifer (INFN underground laboratories, central Italy)

    NASA Astrophysics Data System (ADS)

    Amoruso, A.; Crescentini, L.; Martino, S.; Petitta, M.; Tallini, M.

    2014-06-01

    The Gran Sasso massif is a carbonate fractured aquifer with a spring discharge of more than 18 m3 s-1. The water table has been partially drained by two motorway tunnels and an underground laboratory (UL), located into the core aquifer. Karst features have limited role below the water table, where groundwater flow is mainly regulated by the fracture network. Two paired laser extensometers (BA and BC) recorded ground deformation in the UL. Changes in deformation correlate with the seasonal recharge/discharge cycle of groundwater flow and its long-term changes. Hydrostatic conditions prevail during the recharge phases because of the low permeability of local fractures, favoring compression, and hydraulic gradient increase above the UL. Fast groundwater flow through the high-permeability fault outcropping in the UL can enhance local dilatation for short periods. Spring discharge during exhaustion periods is fed by the low-permeability fracture network, fostering hydrodynamic conditions by hydraulic gradient decrease, diminishing compression and consequently favoring dilatation. Independent support to this conceptual model comes from local tests and a numerical model which highlights the hydromechanical strain effects induced by the hydrological cycle on the jointed rock mass along BA and the role of the hydraulic gradient on the rock mass deformation.

  15. The third aldo castaneda lecture: the neglect of neonatal/infant cardiac disease in Africa--continental genocide?

    PubMed

    Kinsley, Robin H

    2012-04-01

    The advances made in pediatric cardiology and cardiac surgery now make it possible for survival into adulthood of the majority of children born with congenitally malformed hearts. On the African continent, unfortunately, this is only a dream as roughly 280,000 neonates born every year on the continent are left untreated, demonstrating the natural history of the congenitally malformed heart by default. Pediatric cardiac surgery is available in very few countries on this continent. This article takes a look at the problem of neonates and infants born with cardiac defects on the continent and attempts an extrapolation of the magnitude of the problem. Using the experience gained at the Walter Sisulu Pediatric Cardiac Center since its inception in 2003, issues of financing indigent patients, training local personnel, and building capacity through infrastructure development and regional cooperation are discussed. The success of the Walter Sisulu model demonstrates the benefits of treatment for the neonates and infants with congenitally malformed heart, on the continent. It is emphasized that African governments and all stakeholders must participate to ensure a good outcome for the African child with congenital cardiac defect.

  16. Aldo-keto Reductase Family 1 Member B 10 Mediates Liver Cancer Cell Proliferation through Sphingosine-1-Phosphate

    PubMed Central

    Jin, Junfei; Liao, Weijia; Yao, Wenmin; Zhu, Rongping; Li, Yulan; He, Songqing

    2016-01-01

    AKR1B10 is involved in hepatocarcinogenesis via modulation of fatty acid and lipid synthesis. AKR1B10 inhibition results in apoptosis of tumor cells whose lipids, especially phospholipids, were decreased by over 50%, suggesting involvement of phospholipids like sphingosine-1-phosphate (S1P) in AKR1B10’s oncogenic function. Using a co-culture system, we found that co-culture of QSG-7701 (human hepatocyte) with HepG2 (hepatoma cell line) increases QSG-7701’s proliferation, in which AKR1B10-S1P signaling plays a pivotal role. Consistent with previous findings, AKR1B10 mRNA and protein levels were higher in primary hepatocellular carcinoma (PHC) tissues than in peri-tumor tissues. Interestingly, the level of S1P was also higher in PHC tissues than in peri-tumor tissues. After analyzing the correlation between AKR1B10 mRNA expression in PHC tissues and the clinical data, we found that AKR1B10 mRNA expression was associated with serum alpha-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, and lymph node metastasis, but not with other clinicopathologic variables. A higher AKR1B10 mRNA expression level is related to a shorter DFS (disease free survival) and OS (overall survival), serving as an independent predictor of DFS and OS in PHC patients with surgical resection. PMID:26948042

  17. Crystal structure of perakine reductase, founding member of a novel aldo-keto reductase (AKR) subfamily that undergoes unique conformational changes during NADPH binding.

    PubMed

    Sun, Lianli; Chen, Yixin; Rajendran, Chitra; Mueller, Uwe; Panjikar, Santosh; Wang, Meitian; Mindnich, Rebekka; Rosenthal, Cindy; Penning, Trevor M; Stöckigt, Joachim

    2012-03-30

    Perakine reductase (PR) catalyzes the NADPH-dependent reduction of the aldehyde perakine to yield the alcohol raucaffrinoline in the biosynthetic pathway of ajmaline in Rauvolfia, a key step in indole alkaloid biosynthesis. Sequence alignment shows that PR is the founder of the new AKR13D subfamily and is designated AKR13D1. The x-ray structure of methylated His(6)-PR was solved to 2.31 Å. However, the active site of PR was blocked by the connected parts of the neighbor symmetric molecule in the crystal. To break the interactions and obtain the enzyme-ligand complexes, the A213W mutant was generated. The atomic structure of His(6)-PR-A213W complex with NADPH was determined at 1.77 Å. Overall, PR folds in an unusual α(8)/β(6) barrel that has not been observed in any other AKR protein to date. NADPH binds in an extended pocket, but the nicotinamide riboside moiety is disordered. Upon NADPH binding, dramatic conformational changes and movements were observed: two additional β-strands in the C terminus become ordered to form one α-helix, and a movement of up to 24 Å occurs. This conformational change creates a large space that allows the binding of substrates of variable size for PR and enhances the enzyme activity; as a result cooperative kinetics are observed as NADPH is varied. As the founding member of the new AKR13D subfamily, PR also provides a structural template and model of cofactor binding for the AKR13 family. PMID:22334702

  18. Citrate-Linked Keto- and Aldo-Hexose Monosaccharide Cellulose Conjugates Demonstrate Selective Human Neutrophil Elastase-Lowering Activity in Cotton Dressings

    PubMed Central

    Edwards, Judson V.; Caston-Pierre, Sonya

    2013-01-01

    Sequestration of harmful proteases as human neutrophil elastase (HNE) from the chronic wound environment is an important goal of wound dressing design and function. Monosaccharides attached to cellulose conjugates as ester-appended aldohexoses and ketohexoses were prepared on cotton gauze as monosccharide-citrate-cellulose-esters for HNE sequestration. The monosaccharide-cellulose analogs demonstrated selective binding when the derivatized cotton dressings were measured for sequestration of HNE. Each monosaccharide-cellulose conjugate was prepared as a cellulose citrate-linked monosaccharide ester on the cotton wound dressing, and assayed under wound exudate-mimicked conditions for elastase sequestration activity. A series of three aldohexose and four ketohexose ester cellulose conjugates were prepared on cotton gauze through citric acid-cellulose cross linking esterification. The monosaccharide portion of the conjugate was characterized by hydrolysis of the citrate-monosaccharide ester bond, and subsequent analysis of the free monosaccharide with high performance anion exchange chromatography. The ketohexose and aldohexose conjugate levels on cotton were quantified on cotton using chromatography and found to be present in milligram/gram amounts. The citrate-cellulose ester bonds were characterized with FTIR. Ketohexose-citrate-cellulose conjugates sequestered more elastase activity than aldohexose-citrate-cellulose conjugates. The monosaccharide cellulose conjugate families each gave distinctive profiles in elastase-lowering effects. Possible mechanisms of elastase binding to the monosaccharide-cellulose conjugates are discussed. PMID:24955952

  19. The contribution of forensic geology and other trace evidence analysis to the investigation of the killing of Italian Prime Minister Aldo Moro.

    PubMed

    Lombardi, G

    1999-05-01

    In May 1978 the body of the kidnapped Italian Prime Minister, murdered by the Red Brigades, was found in a car parked in the center of Rome. This paper discusses the findings from the investigations conducted on the evidence found on Mr. Moro's clothes, shoes (beach sand, bitumen, vegetals and polyester fragments), and on the car. To get a comprehensive picture of the characteristics of the various pieces of evidence, use was made of a multiple-technique approach. The sand was identified as coming from the seashore close to Rome. A tract of shore with a limited number of roads leading to the beach was defined as compatible with the textural and compositional characteristics of the sand. The study of the vegetal fragmenta suggested that they had been picked up in a period of time close to the killing. Thermosetting polyester, of the type used in boat manufacturing was found under the fenders, in the tires and inside the car, as well as under Mr. Moro's shoes, supporting proximity of a beach. Pollen analysis showed that adhesion of volcanic soil to the car fenders antedated adhesion of the sand.

  20. Proceedings of the Conference of the International Group for the Psychology of Mathematics Education (29th, Melbourne, Australia, July 10-15, 2005). Volume 3

    ERIC Educational Resources Information Center

    Chick, Helen L., Ed.; Vincent, Jill L., Ed.

    2005-01-01

    The third volume of the 29th annual conference of the International Group for the Psychology of Mathematics Education contains full research report papers. Papers include: (1) Students' Use of ICT Tools: Choices and Reasons (Anne Berit Fuglestad); (2) Interaction of Modalities in Cabri: A Case Study (Fulvia Furinghetti, Francesca Morselli, and…

  1. X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP(+) and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity.

    PubMed

    Ruiz, Francesc Xavier; Cousido-Siah, Alexandra; Mitschler, André; Farrés, Jaume; Parés, Xavier; Podjarny, Alberto

    2013-02-25

    Only one crystal structure is currently available for tumor marker AKR1B10, complexed with NADP(+) and tolrestat, which is an aldose reductase inhibitor (ARI) of the carboxylic acid type. Here, the X-ray structure of the complex of the V301L substituted AKR1B10 holoenzyme with fidarestat, an ARI of the cyclic imide type, was obtained at 1.60Å resolution by replacement soaking of crystals containing tolrestat. Previously, fidarestat was found to be safe in phase III trials for diabetic neuropathy and, consistent with its low in vivo side effects, was highly selective for aldose reductase (AR or AKR1B1) versus aldehyde reductase (AKR1A1). Now, inhibition studies showed that fidarestat was indeed 1300-fold more selective for AR as compared to AKR1B10, while the change of Val to Leu (found in AR) caused a 20-fold decrease in the IC50 value with fidarestat. Structural analysis of the V301L AKR1B10-fidarestat complex displayed enzyme-inhibitor interactions similar to those of the AR-fidarestat complex. However, a close inspection of both the new crystal structure and a computer model of the wild-type AKR1B10 complex with fidarestat revealed subtle changes that could affect fidarestat binding. In the crystal structure, a significant motion of loop A was observed between AR and V301L AKR1B10, linked to a Phe-122/Phe-123 side chain displacement. This was due to the presence of the more voluminous Gln-303 side chain (Ser-302 in AR) and of a water molecule buried in a subpocket located at the base of flexible loop A. In the wild-type AKR1B10 model, a short contact was predicted between the Val-301 side chain and fidarestat, but would not be present in AR or in V301L AKR1B10. Overall, these changes could contribute to the difference in inhibitory potency of fidarestat between AR and AKR1B10.

  2. Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis.

    PubMed

    van Bloois, Edwin; Winter, Remko T; Janssen, Dick B; Fraaije, Marco W

    2009-06-01

    Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes. PMID:19224207

  3. Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

    PubMed Central

    Guo, Honglei; Li, Hongmei; Ling, Lilu

    2016-01-01

    Aldosterone (Aldo) is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER) stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA), and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo. PMID:27721575

  4. 76 FR 22862 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... and unconfined types of recreational experiences. The Aldo Leopold Wilderness Research Institute will... a currently valid OMB control number. 30-Day Federal Register Notice Forest Service Title: Aldo Leopold Wilderness Research Institute Wilderness Visitor Study. OMB Control Number: 0596-NEW. Summary...

  5. Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells.

    PubMed

    Bordin, Luciana; Saccardi, Carlo; Donà, Gabriella; Sabbadin, Chiara; Andrisani, Alessandra; Ambrosini, Guido; Plebani, Mario; Brunati, Anna Maria; Ragazzi, Eugenio; Gizzo, Salvatore; Armanini, Decio

    2016-01-01

    We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments. PMID:27158328

  6. 78 FR 6805 - Information Collection: Arctic National Wildlife Refuge Recreation Visitor Study-2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-31

    ... concerning this notice should be addressed to Alan E. Watson, Aldo Leopold Wilderness Research Institute, USDA Forest Service Rocky Mountain Research Station, 790 E. Beckwith Ave., Missoula, MT 59801. Comments... may inspect comments received at the Aldo Leopold Wilderness Research Institute, USDA Forest...

  7. Mineralocorticoid receptor is involved in the aldosterone pathway in human red blood cells

    PubMed Central

    Bordin, Luciana; Saccardi, Carlo; Donà, Gabriella; Sabbadin, Chiara; Andrisani, Alessandra; Ambrosini, Guido; Plebani, Mario; Brunati, Anna Maria; Ragazzi, Eugenio; Gizzo, Salvatore; Armanini, Decio

    2016-01-01

    We have recently demonstrated that excessive aldosterone (Aldo) secretion in primary aldosteronism (PA) is associated with red blood cells (RBC) senescence. These alterations were prevented/inhibited by cortisol (Cort) or canrenone (Can) raising the hypothesis that Aldo effects in RBC may be mediated by mineralocorticoid receptor (MR), though to date MR has never been demonstrated in human RBC. The aim of this multicenter comparative study was to investigate whether Aldo effects were mediated by MR in these a-nucleated cells. We included 12 healthy controls (HC) and 22 patients with PA. MR presence and activation were evaluated in RBC cytosol by glycerol gradient sedimentation, Western blotting, immuno-precipitation and radioimmunoassay. We demonstrated that RBC contained cytosolic MR, aggregated with HSP90 and other proteins to form multiprotein complex. Aldo induced MR to release from the complex and to form MR dimers which were quickly proteolyzed. Cort induced MR release but not dimers formation while Can was not able to induce MR release. In addition, RBC cytosol from PA patients contained significantly higher amounts of both MR fragments (p<0.0001) and Aldo (p<0.0001) concentrations. In conclusion, in RBC a genomic-like Aldo pathway is proposed involving MR activation, dimerization and proteolysis, but lacking nuclear transcription. In addition, dimers proteolysis may ensure a sort of Aldo scavenging from circulation by entrapping Aldo in MR fragments. PMID:27158328

  8. PREFACE: 12th Conference on ''Theoretical Nuclear Physics in Italy''

    NASA Astrophysics Data System (ADS)

    Bombaci, I.; Covello, A.; Marcucci, L. E.; Rosati, S.

    2009-07-01

    These Proceedings contain the invited and contributed papers presented at the 12th Conference on Theoretical Nuclear Physics in Italy held in Cortona, Italy, from 8-10 October 2008. As usual, the meeting was held at il Palazzone, a 16th century castle owned by the Scuola Normale Superiore di Pisa. The aim of this biennal conference is to bring together Italian theorists working in various fields of Nuclear Physics to discuss their latest results and confront their points of view in a lively and informal way. This offers the opportunity to promote collaborations between different groups. There were about 50 participants at the conference, coming from 14 Italian Universities (Cagliari, Catania, Ferrara, Firenze, Genova, Lecce, Milano, Napoli, Padova, Pavia, Pisa, Roma, Trento, Trieste). The program of the conference, prepared by the Organizing Committee (Ignazio Bombaci, Aldo Covello, Laura Elisa Marcucci and Sergio Rosati) focused on six main topics: Few-Nucleon Systems, Nuclear Matter and Nuclear Dynamics, Nuclear Astrophysics, Structure of Hadrons and Hadronic Matter, Nuclear Structure, Nuclear Physics with Electroweak Probes. Winfried Leidemann, Maria Colonna, Marcello Lissia, Elena Santopinto, Silvia Lenzi and Omar Benhar took the burden of giving general talks on these topics and reviewing the research activities of the various Italian groups. In addition, 19 contributed papers were presented, most of them by young participants. In the last session of the Conference there were two invited talks related to experimental activities of great current interest. Gianfranco Prete from the Laboratori Nazionali di Legnaro spoke about the Italian radioactive ion beam facility SPES and the status of the European project EURISOL, while Nicola Colonna from the INFN, Bari, gave an overview of the perspectives of development of fourth-generation nuclear reactors. We would like to thank the authors of the general reports for their hard work in reviewing the main achievements in

  9. Age-related changes in thirst, salt appetite, and arterial blood pressure in response to aldosterone-dexamethasone combination in rats

    PubMed Central

    Xue, Baojian; Beltz, Terry G.; Johnson, Alan Kim

    2015-01-01

    This work examined the effects of age on daily water and sodium ingestion and cardiovascular responses to chronic administration of the mineralocorticoid, aldosterone (ALDO) either alone or together with the glucocorticoid, dexamethasone (DEX). Young (4 mo), adult (12 mo), and aged (30 mo) male Brown Norway rats were prepared for continuous telemetry recording of blood pressure (BP) and heart rate (HR). Baseline water and sodium (i.e., 0.3 M NaCl) intake, BP, and HR were established for 10 days. Then ALDO (60 μg/day sc) was infused alone, or together with DEX (2.5 or 20 μg/day sc), for another 10 days. Compared with baseline levels, ALDO stimulated comparable increases in daily saline intake at all ages. ALDO together with the higher dose of DEX (i.e., ALDO/DEX20) increased daily saline intake more than did ALDO, but less so in aged rats. Infusion of ALDO/DEX20 increased mean arterial pressure (MAP), and decreased HR, more than did infusion of ALDO. The changes in MAP in response to both treatments depended on age. For all ages, MAP and saline intake increased simultaneously during ALDO, while MAP always increased before saline intake did during ALDO/DEX20. Contrary to our predictions, MAP did not increase more in old rats in response to either treatment. We speculate that age-related declines in cardiovascular responses to glucocorticoids contributed to the attenuated increases in sodium intake in response to glucocorticoids that were observed in older animals. PMID:25833938

  10. Wars and suicides in Israel, 1948-2006.

    PubMed

    Oron Ostre, Israel

    2012-05-01

    This paper reports the characteristics of suicides which occurred during the existential and the non-existential wars in Israel. It provides a first approximation of whether the suicide patterns in each war are consistent with the findings of Morselli and Durkheim, and whether their theoretical interpretations can serve as a preliminary guideline to explaining the Israeli case, which is characterized by short periods of war, social integration during some of the non-existential wars, and a sharp rise in post-war male suicide rates following all of the existential wars. Implications for further studies on the subject in Israel and elsewhere are discussed.

  11. Wars and Suicides in Israel, 1948–2006

    PubMed Central

    Oron (Ostre), Israel

    2012-01-01

    This paper reports the characteristics of suicides which occurred during the existential and the non-existential wars in Israel. It provides a first approximation of whether the suicide patterns in each war are consistent with the findings of Morselli and Durkheim, and whether their theoretical interpretations can serve as a preliminary guideline to explaining the Israeli case, which is characterized by short periods of war, social integration during some of the non-existential wars, and a sharp rise in post-war male suicide rates following all of the existential wars. Implications for further studies on the subject in Israel and elsewhere are discussed. PMID:22754482

  12. Aldosterone aggravates glucose intolerance induced by high fructose.

    PubMed

    Sherajee, Shamshad J; Rafiq, Kazi; Nakano, Daisuke; Mori, Hirohito; Kobara, Hideki; Hitomi, Hirofumi; Fujisawa, Yoshihide; Kobori, Hiroyuki; Masaki, Tsutomu; Nishiyama, Akira

    2013-11-15

    We previously reported that aldosterone impaired vascular insulin signaling in vivo and in vitro. Fructose-enriched diet induces metabolic syndrome including hypertension, insulin resistance, hyperlipidemia and diabetes in animal. In the current study, we hypothesized that aldosterone aggravated fructose feeding-induced glucose intolerance in vivo. Rats were divided into five groups for six-week treatment; uninephrectomy (Unx, n=8), Unx+aldosterone (aldo, 0.75 µg/h, s.c., n=8), Unx+fructose (fruc, 10% in drinking water, n=8), Unx+aldo+fruc, (aldo+fruc, n=8), and Unx+aldo+fruc+spironolactone, a mineralocorticoid receptor antagonist (aldo+fruc+spiro, 20mg/kg/day, p.o., n=8). Aldo+fruc rats manifested the hypertension, and induced glucose intolerance compared to fruc intake rats assessed by oral glucose tolerance test, homeostasis model assessment of insulin resistance and hyperinsulinemic-euglycemic clamp study. Spironolactone, significantly improved the aldosterone-accelerated glucose intolerance. Along with improvement in insulin resistance, spironolactone suppressed upregulated mineralocorticoid receptor (MR) target gene, serum and glucocorticoid-regulated kinases-1 mRNA expression in skeletal muscle in aldo+fruc rats. In conclusion, these data suggested that aldosterone aggravates fructose feeding-induced glucose intolerance through MR activation.

  13. Aldosterone diurnal rhythm in the rat: a question of cross-reactivity?

    PubMed

    Bligh, M E; Bhagwat, S A; Castonguay, T W

    1993-05-01

    Radioimmunoassay (RIA) of plasma aldosterone (ALDO) can be hampered by cross-reactivity with plasma corticosterone (CORT). The purpose of this study was to determine and adjust for CORT crossreactivity when assaying for ALDO in blood samples taken throughout a 24-h period. Plasma was obtained from 10 adrenalectomized male Sprague-Dawley rats. Corticosterone-free plasma was spiked with 0, 50, 75, 100, 150, 200, and 300 ng/ml CORT. Aldosterone determination was performed by RIA. An equation for ALDO concentration adjusted for plasma CORT concentration was calculated (ALDO = measurable ALDO - 0.377 x CORT - 5.324). Twenty male Sprague-Dawley rats were adapted to a 12/12 light/dark cycle (lights on at 0900 h). They were divided into two groups based on body weight. Blood samples were obtained every 4 h beginning at 0900 h from rats in group 1 and beginning at 1100 h from rats in group 2. Distinct diurnal CORT and ALDO rhythms were observed. Corticosterone levels were highest at 2100 h (131.8 +/- 17.8 ng/ml) and lowest at 1300 h (04.6 +/- 1.8 ng/ml). Aldosterone levels were highest at 1900 h (276.50 +/- 53.60 pg/ml) and lowest at 1500 h (27.53 +/- 6.84 pg/ml). Corticosterone and ALDO levels were often significantly correlated (r > 0.60), but not at times when CORT and ALDO levels were at their highest. These results suggest that ALDO and CORT may be regulated by different mechanisms or may have a regulatory influence upon each other throughout the day/night cycle.

  14. Spironolactone and canrenone inhibit UGT2B7-catalyzed human liver and kidney microsomal aldosterone 18beta-glucuronidation: a potential drug interaction.

    PubMed

    Knights, Kathleen M; Bowalgaha, Kushari; Miners, John O

    2010-07-01

    Elevated plasma concentrations of aldosterone (ALDO) are observed in patients treated with spironolactone. Because ALDO is eliminated via UGT2B7-catalyzed 18beta-glucuronidation, this study aimed to determine whether spironolactone and its primary metabolites, canrenone and canrenoic acid, inhibit ALDO 18beta-glucuronidation by recombinant UGT2B7 and by human liver (HLM) and human kidney cortical (HKCM) microsomes. Initial experiments characterized the effects of all three compounds on 4-methylumbelliferone and ALDO glucuronidation by recombinant human UGT2B7. IC(50) values for spironolactone and canrenone ranged from 26 to 50 microM, whereas canrenoic acid was a weak inhibitor. Inhibitor constant (K(i)) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation were subsequently determined with HLM, HKCM, and UGT2B7 as the enzyme sources. Spironolactone and canrenone were competitive inhibitors of ALDO 18beta-glucuronidation by HLM, HKCM, and UGT2B7. Mean (+/-) K(i) values for spironolactone were 52 +/- 22 (HLM) and 34 +/- 4 microM (HKCM), and mean (+/-) K(i) values for canrenone were 41 +/- 19 (HLM) and 23 +/- 2 microM (HKCM). K(i) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation by recombinant UGT2B7 were 23 and 11 microM, respectively. "Actual" K(i) values for spironolactone and canrenone inhibition of ALDO 18beta-glucuronidation, which take into account the role of endogenous microsomal inhibitors, are predicted to be 3 to 5 and 2 to 4 microM, respectively. The data indicate that the elevated ALDO concentrations observed in patients treated with spironolactone may be due, at least in part, to a pharmacokinetic interaction, and spironolactone and canrenone should be considered to be potential inhibitors of the UGT2B7-mediated metabolic clearance of drugs in both liver and kidney. PMID:20304966

  15. Enhanced expression of bone morphogenetic protein system in aldosterone-treated mouse kidneys.

    PubMed

    Suzuki, Jiro; Otsuka, Fumio; Matsumoto, Yoshinori; Inagaki, Kenichi; Miyoshi, Tomoko; Takeda, Masaya; Tsukamoto, Naoko; Nakamura, Eri; Ogura, Kanako; Makino, Hirofumi

    2012-03-01

    Recent studies have shown that bone morphogenetic proteins (BMPs), particularly BMP-7, have an inhibitory role in the development of various renal diseases. We previously reported antagonistic effects of BMPs on renal mesangial cell proliferation induced by aldosterone (Aldo) in vitro. In the present study, we investigated in vivo roles of BMPs in Aldo-induced renal glomerular injury. BALB/c mice aged 6 weeks were treated with Aldo injection (5 μg per day, intraperitoneally) and/or oral administration of high-salt (2%) water for 9 weeks. Systemic blood pressure, body weight, kidney weight and daily proteinuria were not significantly changed by Aldo and/or high-salt treatment. However, renal histological examination revealed increases in glomerular cellularity and glomerular diameter in the groups treated with Aldo injection and high-salt administration. Immunohistochemistry demonstrated expression of BMP-4 and -7 in the glomerular mesangial region. Aldo causes renal glomerular damage by stimulating mesangial cell proliferation and increasing extracellular matrix via the mineralocorticoid receptor (MR). MR messenger RNA (mRNA) expression in the renal cortex was transiently increased by 3-week treatment with Aldo and high-salt intake, but was decreased by 9-week treatment. Furthermore, the expression levels of BMP-4 and -7 mRNA were enhanced in the renal cortex treated with Aldo and high-salt administration. These findings suggest that the renal BMP system is activated by Aldo under the condition of high-salt exposure, which may have a key role in antagonizing glomerular damage in vivo.

  16. Managing for resilience

    EPA Science Inventory

    Early efforts in wildlife management focused on reducing population variability and maximizing yields of select species. Aldo Leopold proposed the concept of habitat management as superior to population management. More recently, ecosystem management, whereby ecological processes...

  17. The Structure of the Nucleon, Three Decades of Investigation (1967-2004)

    NASA Astrophysics Data System (ADS)

    Bodek, Arie

    2005-02-01

    A personal historical account of three decades of experiments that led to a detailed understanding of the structure of the nucleon and the theory of Quantum Chromodynamics. (Panofsky Prize 2004 Talk, Presented at NuInt04, Mar. 2004, Laboratori Nazionali del Gran Sasso - INFN - Assergi, Italy [ http://nuint04.lngs.infn.it/])

  18. Early effects of aldosterone on Na-K pump in rat cortical collecting tubules

    SciTech Connect

    Fujii, Y.; Takemoto, F.; Katz, A.I. )

    1990-07-01

    Sustained exposure to aldosterone (Aldo) increases the abundance and activity of the Na-K pump in cortical collecting tubules (CCT). However, the onset and mechanism of the early interaction of Aldo with the CCT pump, especially in adrenal-intact animals, are unclear. We evaluated the short-term effects of the hormone on Na-K-adenosinetriphosphatase (ATPase) activity and on ouabain-sensitive 86Rb uptake, a measure of the transporting rate of the pump, in microdissected CCT from adrenal-intact rats. Incubation with Aldo (10(-8) M, 2 h) had no effect on Na-K-ATPase activity (Vmax), whereas it produced at least a twofold increase in 86Rb uptake. This effect was generated by physiological concentrations of the hormone (threshold 10(-10) M; apparent K1/2 approximately 10(-9) M), after a short lag of less than or equal to 30 min. Incubation with Aldo in the presence of amiloride or nystatin or in a Na-free medium (choline chloride) did not prevent the enhanced 86Rb uptake seen after Aldo alone; possible interpretations of these observations are discussed. We conclude that Aldo produces a rapid stimulation of pump function in CCT that precedes its induction of new pump synthesis; the physiological significance of this effect is suggested by its occurrence in tubules from adrenal-intact animals within the time frame and concentration range of the hormone's effects on electrolyte transport.

  19. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    PubMed Central

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  20. Low Na, High K Diet and the Role of Aldosterone in BK-Mediated K Excretion

    PubMed Central

    Cornelius, Ryan J.; Wen, Donghai; Li, Huaqing; Yuan, Yang; Wang-France, Jun; Warner, Paige C.; Sansom, Steven C.

    2015-01-01

    A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular (CV) disease in many societies. Part of the benefit of LNaHK relies on its diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not understood. LNaHK mice exhibit an increase in renal K secretion that is dependent on the large, Ca-activated K channel, (BK-α with accessory BK-β4; BK-α/β4). We hypothesized that aldo causes an osmotic diuresis by increasing BK-α/β4-mediated K secretion in LNaHK mice. We found that the plasma aldo concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham), adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate, transtubular K gradient (TTKG), and BK-α and BK-β4 expressions, were decreased in ADX-LA, but not different in ADX-HA. BK-β4 knockout (β4KO) and WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in sham and ADX-HA, the K clearance and TTKG of β4KO were less than WT. In response to amiloride treatment, the osmolar clearance was increased in WT Con, decreased in WT LNaHK, and unchanged in β4KO LNaHK. These data show that the high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-α/β4-mediated K secretion, which creates an osmotic diuresis that may contribute to a reduction in CV disease. PMID:25607984

  1. Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability.

    PubMed

    Miró, Lluïsa; Pérez-Bosque, Anna; Maijó, Mònica; Amat, Concepció; Naftalin, Richard J; Moretó, Miquel

    2013-05-01

    In vivo studies show that raised aldosterone (Aldo) during low-Na adaptation regulates the growth of pericryptal myofibroblasts and reduces the permeability of the colonic epithelium. The aim of this study was to reproduce in vitro the in vivo condition of increased Aldo using human CCD-18Co myofibroblasts and T84 colonic epithelial cells to measure myofibroblast and epithelial proliferation and the expression of intercellular junction proteins. Proliferation was quantified by measuring 5-bromo-2'-deoxyuridine incorporation. The myofibroblast expression of EGF, VEGFa, and transforming growth factor-β1 (TGF-β1) was measured by real-time PCR and the expression of junctional complex proteins by Western blot. Aldo stimulated the proliferation of myofibroblasts by 70% (P < 0.05) and increased EGF mRNA expression by 30% (P < 0.05) without affecting VEGFa and TGF-β1. EGF concentration in the incubation medium increased by 30% (P < 0.05) 24 h after Aldo addition, and these effects were prevented by the addition of spironolactone. Myofibroblast proliferation in response to Aldo was mediated by EGF receptor (EGFR) and involved both MAPKK and phosphatidylinositol 3-kinase pathways. When T84 cells were incubated with medium from myofibroblasts stimulated with Aldo (conditioned medium), the expression of β-catenin and claudin IV was increased by 30% (P < 0.05) and proliferation by 40% (P < 0.05). T84 proliferation decreased when α-EGF, or the EGFR antagonist AG1478, was present. Results in vivo indicate that rats fed a low-salt diet showed an increased expression of EGF and EGFR in the colonic mucosa. These results support the view that changes in colonic permeability during low-Na adaptation are mediated by the EGF secreted by myofibroblasts in response to raised Aldo. PMID:23467299

  2. Time-dependent aldosterone metabolism in toad urinary bladder

    SciTech Connect

    Brem, A.S.; Pacholski, M.; Morris, D.J.

    1988-04-01

    Aldosterone (Aldo) metabolism was examined in the toad bladder. Bladders were incubated with (/sup 3/H)aldosterone (10(-7) M) for 5 h, 1 h, or 10 min. Tissues were analyzed for metabolites using high-pressure liquid chromatography (HPLC). In separate experiments, Na+ transport was assessed by the short-circuit current (SCC) technique. Following a 5-h tissue incubation, about 25% of the (/sup 3/H)-aldosterone was converted into metabolites including a polar monosulfate metabolite, 20 beta-dihydroaldo (20 beta-DHAldo), small quantities of 5 beta-reduced products, and a variety of 5 alpha-reduced Aldo products including 5 alpha-DHAldo, 3 alpha,5 alpha-tetrahydroaldo (3 alpha,5 alpha-THAldo), and 3 beta,5 alpha-THAldo. Tissues metabolized approximately 10% of the labeled hormone into the same compounds by 1 h. Measurable quantities of these metabolites were also synthesized by bladders exposed to Aldo for only 10 min and then incubated in buffer for an additional 50 min without Aldo. Bladders pretreated with the spironolactone, K+-canrenoate (3.5 X 10(-4) M), and stimulated with Aldo (10(-7) M) generated a peak SCC 44 +/- 6% of that observed in matched pairs stimulated with Aldo (P less than 0.001; n = 6). K+-canrenoate also markedly diminished (/sup 3/H)aldosterone metabolism at both 5 and 1 h. Thus, metabolic transformation of Aldo begins prior to hormone-induced increases in Na+ transport. Both the generation of certain metabolites (e.g., 5 alpha-reductase pathway products) and the increase in Na+ transport can be selectively inhibited by K+-canrenoate.

  3. Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs.

    PubMed

    Armanini, Decio; Sabbadin, Chiara; Donà, Gabriella; Clari, Giulio; Bordin, Luciana

    2014-05-01

    Canrenone is a derivative of spironolactone with lower antiandrogen activity. The drug is used only in few countries and can block all the side effects of aldosterone (ALDO). The drug is effective even in the presence of normal concentrations of ALDO. Mineralcorticoid receptor antagonists block the inflammatory activity of ALDO at the level of target tissues as heart, vessels and mononuclear leukocytes. Canrenone reduces the progression of insulin resistance and of microalbuminuria in type 2 diabetes and other related diseases. Both canrenone and hydrochlorothiazide can enhance the effect of treatment with ACE inhibitors and angiotensin II receptor blockers on microalbuminuria, but ALDO receptor blockers are more active. This different action is due to the fact that only canrenone blocks mineralocorticoid receptors. Serum potassium and renal function should be monitored before and during the treatment. ALDO receptor blockers are recommended in addition to polytherapy for resistant hypertension, but there are no studies on the effect of the drug as first-choice therapy. PMID:24617854

  4. Effects of altitude acclimatization on fluid regulatory hormone response to submaximal exercise.

    PubMed

    Rock, P B; Kraemer, W J; Fulco, C S; Trad, L A; Malconian, M K; Rose, M S; Young, P M; Cymerman, A

    1993-09-01

    To determine the effect of altitude acclimatization on plasma levels of atrial natriuretic peptide (ANP) during submaximal exercise and its relationship with renin and aldosterone, seven male volunteers aged 17-23 yr exercised to exhaustion on a cycle ergometer at 80-85% of their maximum O2 uptake at sea level (SL; 50 m), during 1 h in a hypobaric chamber [acute altitude (AA); 4,300 m], and after 14 or 16 days of residence on the summit of Pikes Peak, CO [chronic altitude (CA); 4,300 m]. Plasma samples taken before exercise, 10 min after the start of exercise, and 5 min postexercise were analyzed for ANP, plasma renin activity (PRA), and aldosterone (ALDO). ANP showed a progressive increase from rest to postexercise [7.49 +/- 1.63 to 11.32 +/- 1.80 (SE) pmol/ml and 6.05 +/- 2.55 to 10.38 +/- 7.20 pmol/ml; P = 0.049, exercise] at SL and AA, respectively, but not at CA (P = 0.039, altitude). Similarly, PRA and ALDO rose from rest to postexercise (P < 0.001, exercise), but the rise in ALDO with exercise was less during AA than during SL and CA (P = 0.002, phase). The decreased ANP levels during exercise after altitude acclimatization, with no change in PRA and ALDO, suggest that ANP has little effect on PRA and ALDO under these conditions.

  5. Acknowledgements

    NASA Astrophysics Data System (ADS)

    2016-07-01

    The Meeting was sponsored by the Istituto Nazionale di Fisica Nucleare (INFN), the Società Italiana di Fisica (SIF), the European Physics Society (EPS), the University of Pisa and the University of Siena.

  6. PVN adenovirus-siRNA injections silencing either NOX2 or NOX4 attenuate aldosterone/NaCl-induced hypertension in mice.

    PubMed

    Xue, Baojian; Beltz, Terry G; Johnson, Ralph F; Guo, Fang; Hay, Meredith; Johnson, Alan Kim

    2012-02-01

    Mineralocorticoid excess increases superoxide production by activating NADPH oxidase (NOX), and intracerebroventricular infusions of NADPH oxidase inhibitors attenuate aldosterone (Aldo)/salt-induced hypertension. It has been hypothesized that increased reactive oxygen species (ROS) in the brain may be a key mechanism in the development of hypertension. The present study investigated the brain regional specificity of NADPH oxidase and the role of NOX2 and NOX4 NADPH oxidase subunits in the hypothalamic paraventricular nucleus (PVN) in Aldo/salt-induced hypertension. PVN injections of adenoviral vectors expressing small interfering (si)RNA targeting NOX2 (AdsiRNA-NOX2) or NOX4 (AdsiRNA-NOX4) mRNAs were used to knock down NOX2 and NOX4 proteins. Three days later, delivery of Aldo (0.2 mg·kg(-1)·day(-1) sc) via osmotic pump commenced and 1% NaCl was provided in place of water. PVN injections of either AdsiRNA-NOX2 or AdsiRNA-NOX4 significantly attenuated the development of Aldo/NaCl-induced hypertension. In an additional study, Aldo/salt-induced hypertension was also significantly attenuated in NOX2 (genomic) knockout mice compared with wild-type controls. When animals from both functional studies underwent ganglionic blockade, there was a reduced fall in blood pressure in the NOX2 and NOX4 knockdown/knockout mice. Western blot analyses of the PVN of siRNA-NOX2- or siRNA-NOX4-injected mice confirmed a marked reduction in the expression of NOX2 or NOX4 protein. In cultured PVN neurons, silencing either NOX2 or NOX4 protein production by culturing PVN cells with siRNA-NOX2 or siRNA-NOX4 attenuated Aldo-induced ROS. These data indicate that both NOX2 and NOX4 in the PVN contribute to elevated sympathetic activity and the hypertensivogenic actions induced by mineralocorticoid excess. PMID:22140041

  7. Guanylyl cyclase/natriuretic peptide receptor-A gene disruption causes increased adrenal angiotensin II and aldosterone levels.

    PubMed

    Zhao, Di; Vellaichamy, Elangovan; Somanna, Naveen K; Pandey, Kailash N

    2007-07-01

    Disruption of the guanylyl cyclase-A/natriuretic peptide receptor-A (GC-A/NPRA) gene leads to elevated arterial blood pressure and congestive heart failure in mice lacking NPRA. This study was aimed at determining whether Npr1 (coding for GC-A/NPRA) gene copy number affects adrenal ANG II and aldosterone (Aldo) levels in a gene-dose-dependent manner in Npr1 gene-targeted mice. Adrenal ANG II and Aldo levels increased in 1-copy mice compared with 2-copy mice, but decreased in 3-copy and 4-copy mice. In contrast, renal ANG II levels decreased in 1-copy (25%), 3-copy (38%), and 4-copy (39%) mice compared with 2-copy mice. The low-salt diet stimulated adrenal ANG II and Aldo levels in 1-copy (20 and 2,441%), 2-copy (15 and 2,339%), 3-copy (20 and 424%), and 4-copy (31 and 486%) mice, respectively. The high-salt diet suppressed adrenal ANG II and Aldo levels in 1-copy (46 and 29%) and 2-copy (38 and 17%) mice. On the other hand, the low-salt diet stimulated renal ANG II levels in 1-copy (45%), 2-copy (45%), 3-copy (59%), and 4-copy (48%) mice. However, the high-salt diet suppressed renal ANG II levels in 1-copy (28%) and 2-copy (27%) mice. In conclusion, NPRA signaling antagonizes adrenal ANG II and Aldo levels in a gene-dose dependent manner. Increased adrenal ANG II and Aldo levels may play an important role in elevated arterial blood pressure and progressive hypertension, leading to renal and vascular injury in Npr1 gene-disrupted mice.

  8. Additional use of an aldosterone antagonist in patients with mild to moderate chronic heart failure: a systematic review and meta-analysis

    PubMed Central

    Hu, Li-jun; Chen, Yun-qing; Deng, Song-bai; Du, Jian-lin; She, Qiang

    2013-01-01

    Aims Aldosterone antagonists (AldoAs) have been used to treat severe chronic heart failure (CHF).There is uncertainty regarding the efficacy of using AldoAs in mild to moderate CHF with New York Heart Association (NYHA) classifications of I to II. This study summarizes the evidence for the efficacy of spironolactone (SP), eplerenone (EP) and canrenone in mild to moderate CHF patients. Methods PubMed, MEDLINE, EMBASE and OVID databases were searched before June 2012 for randomized and quasi-randomized controlled trials assessing AldoA treatment in CHF patients with NYHA classes I to II. Data concerning the study's design, patients' characteristics and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) or standardized mean difference were calculated using either fixed or random effects models. Results Eight trials involving 3929 CHF patients were included. AldoAs were superior to the control in all cause mortality (RR 0.79, 95% CI 0.66, 0.95) and in re-hospitalization for cardiac causes (RR 0.62, 95% CI 0.52, 0.74), the left ventricular ejection fraction was improved by AldoA treatment (WMD 2.94%, P = 0.52). Moreover, AldoA therapy decreased the left ventricular end-diastolic volume (WMD −14.04 ml, P < 0.00001),the left ventricular end-systolic volume (WMD −14.09 ml, P < 0.00001). A stratified analysis showed a statistical superiority in the benefits of SP over EP in reducing LVEDV and LVESV. AldoAs reduced B-type natriuretic peptide concentrations (WMD −37.76 pg ml−1, P < 0.00001), increased serum creatinine (WMD 8.69 μmol l−1, P = 0.0003) and occurrence of hyperkalaemia (RR 1.78, 95% CI 1.43, 2.23). Conclusions Additional use of AldoAs in CHF patients may decrease mortality and re-hospitalization for cardiac reasons, improve cardiac function and simultaneously ameliorate LV reverse remodelling. PMID:23088367

  9. WNoDeS, a tool for integrated Grid and Cloud access and computing farm virtualization

    NASA Astrophysics Data System (ADS)

    Salomoni, Davide; Italiano, Alessandro; Ronchieri, Elisabetta

    2011-12-01

    INFN CNAF is the National Computing Center, located in Bologna, Italy, of the Italian National Institute for Nuclear Physics (INFN). INFN CNAF, also called the INFN Tier-1, provides computing and storage facilities to the International High-Energy Physics community and to several multi-disciplinary experiments. Currently, the INFN Tier-1 supports more than twenty different collaborations; in this context, optimization of the usage of computing resources is essential. This is one of the main drivers behind the development of a software called WNoDeS (Worker Nodes on Demand Service). WNoDeS, developed at INFN CNAF and deployed on the INFN Tier-1 production infrastructure, is a solution to virtualize computing resources and to make them available through local, Grid or Cloud interfaces. It is designed to be fully integrated with a Local Resource Management System; it is therefore inherently scalable and permits full integration with existing scheduling, policing, monitoring, accounting and security workflows. WNoDeS dynamically instantiates Virtual Machines (VMs) on-demand, i.e. only when the need arises; these VMs can be tailored and used for purposes like batch job execution, interactive analysis or service instantiation. WNoDeS supports interaction with user requests through traditional batch or Grid jobs and also via the Open Cloud Computing Interface standard, making it possible to allocate compute, storage and network resources on a pay-as-you-go basis. User authentication is supported via several authentication methods, while authorization policies are handled via gLite Argus. WNoDeS is an ambitious solution aimed at virtualizing cluster resources in medium or large scale computing centers, with up to several thousands of Virtual Machines up and running at any given time. In this paper, we descrive the WNoDeS architecture.

  10. CHARACTERIZATION OF STABLE BENZO(A)PYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA

    EPA Science Inventory

    Benzo[alpyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

  11. LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

    EPA Science Inventory

    Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

  12. Eagle Heights Woods: Man's Use of Land.

    ERIC Educational Resources Information Center

    Pratt, Cay; Nelson, Redgy

    This teacher's guide for use in the elementary grades was prepared as a result of the 1970 Local Materials Workshop on Outdoor Education, Madison, Wisconsin. It develops the concept of a land ethnic as expressed by Aldo Leopold in "A Sand County Almanac". A filmstrip is employed to discover the meaning of several words pertinent to…

  13. Landfullness in Adventure-Based Programming: Promoting Reconnection to the Land

    ERIC Educational Resources Information Center

    Baker, Molly

    2005-01-01

    Nearly a half-century ago. Aldo Leopold acknowledged the threat of "landlessness" in our society as measured by the loss of our collective awareness of, and admiration for, the land (Leopold. 1966). At present, this disconnect has evolved to the point where participants in adventure-based programs may find themselves traveling through "Any Woods,…

  14. Productivism and the Product Paradigm in Technological Education

    ERIC Educational Resources Information Center

    Elshof, Leo

    2006-01-01

    Aldo Leopold was a pioneer in United States' wildlife management and his axiom is certainly familiar to anyone who has tried to repair a complex technological system; it applies equally whether one is rebuilding a small block V8 engine or repairing a computer. "Keep all the pieces" is good advice because in all likelihood they will all…

  15. Environmental Literacy in America: What Ten Years of NEETF/Roper Research and Related Studies Say about Environmental Literacy in the U.S.

    ERIC Educational Resources Information Center

    Coyle, Kevin

    2005-01-01

    In 1944, noted conservationist Aldo Leopold wrote: "Acts of conservation without the requisite desires and skill are futile. To create these desires and skills, and the community motive, is the task of education." Almost sixty years later, in January 2003, the National Science Foundation released a report of its Advisory Committee for…

  16. Putting History at the Core: History and Literature in Environmental Studies

    ERIC Educational Resources Information Center

    Morse, Kathryn

    2003-01-01

    When environmental studies programs broaden their curricular offerings into the humanities, their first stop is often environmental literature, particularly classics such as Henry David Thoreau's "Walden," Aldo Leopold's "A Sand County Almanac," and Rachel Carson's "Silent Spring." Environmental literature courses consider many of the works of…

  17. Adventures with Doug: An Interview with Dot Wade, Prairie Botanist.

    ERIC Educational Resources Information Center

    Wiener, Morris; Wade, Dot

    1995-01-01

    The wife of the late Doug Wade discusses the course of his career in outdoor education and nature interpretation; the relationship he had with his mentor, Aldo Leopold; his success as a teacher and his relationship with his students; and how a background in botany enabled her to assist her husband with field trips. (LP)

  18. Caring for Nature 101, or Alternative Perspectives on Educating Natural Resource Managers and Ecologically Conscious Citizens.

    ERIC Educational Resources Information Center

    Booth, Annie L.

    1998-01-01

    Examines the contributions of alternative perspectives from environmental philosophy to university teaching practices that address the question of how to produce ecologically educated citizens. Considers the challenges to modern resource education found in feminist and ecofeminist philosophies and in Aldo Leopold's "Land Ethic." Discusses…

  19. From Romanticism to Deep Ecology: The Continuing Evolution in American Environmental Thought.

    ERIC Educational Resources Information Center

    Ackerson, David

    2000-01-01

    Describes the contributions to deep ecology of Henry Thoreau, who advocated acting upon strongly held convictions; John Muir, who adopted a biocentric view of nature; and Aldo Leopold, who formulated an egalitarian ecosystem ethic. While deep ecology is moving toward a new vision of humankind's relation to nature, it has yet to coalesce into a…

  20. Linking biological conservation to healthy rural communities: a case history of the Janos – Casas Grandes Biosphere Reserve

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the late 1930’s, Aldo Leopold witnessed a striking contrast along the narrow boundary between the United States and Mexico. He later described Mexican ecosystems as a “lovely picture of ecological health” and those same ecosystems north of the U.S. - Mexico border as “so badly damaged that on...

  1. Nature's Web: Caring for the Land. National Wildlife Week Educator's Guide, April 19-25, 1998 = Nature's Web: El Cuidado de la Tierra. National Wildlife Week Guia para el Educador, April 19-25, 1998.

    ERIC Educational Resources Information Center

    Tunstall, Margaret; Kier, Jennifer; Dixon, Cheryl; Bradley, Sara; Hodges, Elenor; Levey, Sharon

    This guide features Aldo Leopold's land ethic woven into a series of activities that also represent the five core issues of most concern to the National Wildlife Federation (NWF): (1) wetlands; (2) water quality; (3) land stewardship; (4) endangered habitats; and (5) sustainable communities. Each activity is introduced by a biographical sketch of…

  2. CHARACTERIZATION OF STABLE BENZOLALPYRENE-7,8-QUINONE-DNA ADDUCTS IN CALF THYMUS DNA AND POLYDEOXYNUCLEOTIDES

    EPA Science Inventory

    Bcnzo[a]pyrene-7,8-dione (BPQ) is a reactive aldo-keto reductase-mediated product of B[a]P-7,8-diol, a major P450/epoxide hydrolase metabolite of the multi-species carcinogen, B[a]P. The role of BPQ in B[a]P's genotoxicity and carcinogenesis is evolving. Toxicity pathways involvi...

  3. Human carbonyl reductase (CBR) localized to band 21q22. 1 by high-resolution fluorescence in situ hybridization displays gene dosage effects in trisomy 21 cells

    SciTech Connect

    Lemieux, N. ); Malfoy, B. ); Forrest, G.L. )

    1993-01-01

    Human carbonyl reductase (CBR) belongs to a group of NADPH-dependent enzymes called aldo-keto reductases. The enzyme can function as an aldo-keto reductase or as a quinone reductase with potential for modulating quinone-mediated oxygen free radicals. The CBR gene was mapped by high-resolution fluorescence in situ hybridization to band 21q22.12, very close to the SOD1 locus at position 2lq22.11. CBR displayed gene dosage effects in trisomy 21 human lymphoblasts at the DNA and mRNA levels. Lymphoblasts with increasing chromosome 21 ploidy also showed increased aldo-keto reductase activity and increased quinone reductase activity. Both aldo-keto reductase activity and quinone reductase activity have been shown to be associated with carbonyl reductase. The location of CBR near SOD1 and the increased enzyme activity and potential for free radical modulation in trisomy 21 cells implicate CBR as a candidate for contributing to the pathology of certain diseases such as Down syndrome and Alzheimer disease. 28 refs., 1 fig., 1 tab.

  4. Dead Wolves, Dead Birds, and Dead Trees: Catalysts for Transformative Learning in the Making of Scientist-Environmentalists

    ERIC Educational Resources Information Center

    Walter, Pierre

    2013-01-01

    This historical study identifies catalysts for transformative learning in the lives of three scientist-environmentalists important to the 20th-century environmental movement: Aldo Leopold, Rachel Carson, and David Suzuki. Following a brief review of theoretical perspectives on transformative learning, the article argues that transformative…

  5. The potential of novel native plant materials for the restoration of novel ecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aldo Leopold is considered by many to be the father of restoration ecology in North America. While a professor of wildlife management at the University of Wisconsin, he labored 13 years to restore a functioning ecosystem to badly damaged Sauk County farmland that he purchased at the height of the G...

  6. Differential responses to salt supplementation in adult male and female rat adrenal glands following intrauterine growth restriction.

    PubMed

    Bibeau, Karine; Otis, Mélissa; St-Louis, Jean; Gallo-Payet, Nicole; Brochu, Michèle

    2011-04-01

    In low sodium-induced intrauterine growth restricted (IUGR) rat, foetal adrenal steroidogenesis as well as the adult renin-angiotensin-aldosterone system (RAAS) is altered. The aim of the present study was to determine the expression of cytochrome P450 aldosterone synthase (P450aldo) and of angiotensin II receptor subtypes 1 (AT(1)R) and 2 (AT(2)R) in adult adrenal glands and whether this expression could be influenced by IUGR and by high-salt intake in a sex-specific manner. After 6 weeks of 0.9% NaCl supplementation, plasma renin activity, P450aldo expression and serum aldosterone levels were decreased in all groups. In males, IUGR induced an increase in AT(1)R, AT(2)R, and P450aldo levels, without changes in morphological appearance of the zona glomerulosa (ZG). By contrast, in females, IUGR had no effect on the expression of AT(1)R, but increased AT(2)R mRNA while decreasing protein expression of AT(2)R and P450aldo. In males, salt intake in IUGR rats reduced both AT(1)R mRNA and protein, while for AT(2)R, mRNA levels decreased whereas protein expression increased. In females, salt intake reduced ZG size in IUGR but had no affect on AT(1)R or AT(2)R expression in either group. These results indicate that, in response to IUGR and subsequently to salt intake, P450aldo, AT(1)R, and AT(2)R levels are differentially expressed in males and females. However, despite these adrenal changes, adult IUGR rats display adequate physiological and adrenal responses to high-salt intake, via RAAS inhibition, thus suggesting that extra-adrenal factors likely compensate for ZG alterations induced by IUGR.

  7. Application of a Bonner sphere spectrometer for the determination of the angular neutron energy spectrum of an accelerator-based BNCT facility.

    PubMed

    Mirzajani, N; Ciolini, R; Di Fulvio, A; Esposito, J; d'Errico, F

    2014-06-01

    Experimental activities are underway at INFN Legnaro National Laboratories (LNL) (Padua, Italy) and Pisa University aimed at angular-dependent neutron energy spectra measurements produced by the (9)Be(p,xn) reaction, under a 5MeV proton beam. This work has been performed in the framework of INFN TRASCO-BNCT project. Bonner Sphere Spectrometer (BSS), based on (6)LiI (Eu) scintillator, was used with the shadow-cone technique. Proper unfolding codes, coupled to BSS response function calculated by Monte Carlo code, were finally used. The main results are reported here.

  8. Validation of pentaacetylaldononitrile derivative for dual 2H gas chromatography/mass spectrometry and 13C gas chromatography/combustion/isotope ratio mass spectrometry analysis of glucose.

    PubMed

    Sauvinet, Valérie; Gabert, Laure; Qin, Du; Louche-Pélissier, Corinne; Laville, Martine; Désage, Michel

    2009-12-01

    A reference method to accurately define kinetics in response to the ingestion of glucose in terms of total, exogenous and endogenous glucose is to use stable-isotope-labelled compounds such as 2H and 13C glucose followed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis. The use of the usual pentaacetyl (5Ac) derivative generates difficulties in obtaining accurate and reproducible results due to the two chromatographic peaks for the syn and anti isomers, and to the isotopic effect occurring during acetylation. Therefore, the pentaacetylaldononitrile derivative (Aldo) was validated for both isotopes, and compared with the 5Ac derivative. A correction factor including carbon atom dilution (stoichiometric equation) and the kinetic isotopic effect (KIE) was determined. Analytical validation results for the 2H GC/MS and 13C GC/C/IRMS measurements produced acceptable results with both derivatives. When 2H enrichments of plasma samples were < or = 1 mol % excess (MPE), the repeatability (RSD(Aldo Intra assay and Intra day) <0.94%, RSD(5Ac Intra assay and Intra day) <3.29%), accuracy (Aldo <3.4%, 5Ac <29.0%), and stability of the derivatized samples were significantly better when the Aldo derivatives of the plasma samples were used (p < 0.05). When the glucose kinetics were assessed in nine human subjects, after glucose ingestion, the plasma glucose 2H enrichments were identical with both derivatives, whereas the 13C enrichments needed a correction factor to fit together. Due to KIE variation, this correction factor was not constant and had to be calculated for each batch of analyses, to obtain satisfactory results. Mean quantities of exogenous glucose exhibit marked difference (20.9 +/- 1.3g (5Ac) vs. 26.7 +/- 2.5g (Aldo)) when calculated with stoichiometric correction, but fit perfectly when calculated after application of the correction factor (22.1 +/- 1.3g (5Ac) vs. 22.9 +/- 1.9g

  9. Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

    PubMed

    Pang, S; Levine, L S; Stoner, E; Opitz, J M; Pollack, M S; Dupont, B; New, M I

    1983-04-01

    In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone

  10. Case report of body dysmorphic disorder in a suicidal patient.

    PubMed

    Zhang, Yingfeng; Ma, Hongxia; Wang, Yanbin

    2016-02-25

    Few reports exist about the treatment of body dysmorphic disorder (BDD) in patients who are suicidal. This case report describes a 19-year-old male with BDD who had delusional-intensity beliefs about facial disfigurement that had gradually intensified over a 2-year period. However, he was initially misdiagnosed with depression partly because he was admitted immediately after a suicide attempt that was associated with depressive symptoms and social withdrawal, symptoms that subsequently proved to be secondary to his BDD. The symptoms resolved completely and his social functioning returned to normal after 8 weeks of inpatient treatment with fluoxetine and cognitive behavioral therapy. This report is a reminder that suicidal behavior and ideation can have many causes; to avoid misdiagnosis and inappropriate treatment, clinicians should consider other possibilities before assuming that suicidal behavior or ideation is the direct result of depression. We discuss the many changes in the understanding and diagnostic classification of BDD since it was first reported by Enrico Morselli in 1886. PMID:27688645

  11. The origins of psychology in Italy: Themes and authors that emerge through a content analysis of the Rivista di Filosofia Scientifica [Journal of Scientific Philosophy].

    PubMed

    Bartolucci, Chiara; Lombardo, Giovanni Pietro

    2012-08-01

    This article examines the scientific-cultural context of the second half of the 1800s, during which psychological science emerged in Italy. The article explores the contribution made by the emergence of the primary research traditions of that period, namely, physiological anthropology and phreniatry, by means of a methodology that combines content analysis with a classical historiographical study of the period. Themes and authors deriving from the various disciplines in the human and natural sciences were identified through a content analysis of the Rivista di Filosofia Scientifica [Journal of Scientific Philosophy], a periodical that is representative of Italian positivism. The analysis highlights the epistemological perspective held by scholars who, distancing themselves from the mechanistic reductionism of the proponents of positivism, integrated a naturalistic and evolutionary conceptualization with the neo-Kantian critique. A clearly delineated naturalistic and differential perspective of scientific research that brought about the birth of psychology as an experimental discipline in Italy in the 1900s emerges from the analysis, including psychology and psychopathology as studied by the phreniatrists Gabriele Buccola, Enrico Morselli, and Eugenio Tanzi; Tito Vignoli and Giuseppe Sergi's work in comparative anthropology; Giulio Fano's approach and contribution to physiology; and Enrico Ferri's contribution to criminology. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID:23397915

  12. Case report of body dysmorphic disorder in a suicidal patient

    PubMed Central

    ZHANG, Yingfeng; MA, Hongxia; WANG, Yanbin

    2016-01-01

    Few reports exist about the treatment of body dysmorphic disorder (BDD) in patients who are suicidal. This case report describes a 19-year-old male with BDD who had delusional-intensity beliefs about facial disfigurement that had gradually intensified over a 2-year period. However, he was initially misdiagnosed with depression partly because he was admitted immediately after a suicide attempt that was associated with depressive symptoms and social withdrawal, symptoms that subsequently proved to be secondary to his BDD. The symptoms resolved completely and his social functioning returned to normal after 8 weeks of inpatient treatment with fluoxetine and cognitive behavioral therapy. This report is a reminder that suicidal behavior and ideation can have many causes; to avoid misdiagnosis and inappropriate treatment, clinicians should consider other possibilities before assuming that suicidal behavior or ideation is the direct result of depression. We discuss the many changes in the understanding and diagnostic classification of BDD since it was first reported by Enrico Morselli in 1886. PMID:27688645

  13. The origins of psychology in Italy: Themes and authors that emerge through a content analysis of the Rivista di Filosofia Scientifica [Journal of Scientific Philosophy].

    PubMed

    Bartolucci, Chiara; Lombardo, Giovanni Pietro

    2012-08-01

    This article examines the scientific-cultural context of the second half of the 1800s, during which psychological science emerged in Italy. The article explores the contribution made by the emergence of the primary research traditions of that period, namely, physiological anthropology and phreniatry, by means of a methodology that combines content analysis with a classical historiographical study of the period. Themes and authors deriving from the various disciplines in the human and natural sciences were identified through a content analysis of the Rivista di Filosofia Scientifica [Journal of Scientific Philosophy], a periodical that is representative of Italian positivism. The analysis highlights the epistemological perspective held by scholars who, distancing themselves from the mechanistic reductionism of the proponents of positivism, integrated a naturalistic and evolutionary conceptualization with the neo-Kantian critique. A clearly delineated naturalistic and differential perspective of scientific research that brought about the birth of psychology as an experimental discipline in Italy in the 1900s emerges from the analysis, including psychology and psychopathology as studied by the phreniatrists Gabriele Buccola, Enrico Morselli, and Eugenio Tanzi; Tito Vignoli and Giuseppe Sergi's work in comparative anthropology; Giulio Fano's approach and contribution to physiology; and Enrico Ferri's contribution to criminology. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  14. FOREWORD: TAUP 2005: Proceedings of the Ninth International Conference on Topics in Astroparticle and Underground Physics

    NASA Astrophysics Data System (ADS)

    Bottino, Alessandro; Coccia, Eugenio; Morales, Julio; Puimedónv, Jorge

    2006-04-01

    The ninth meeting of the TAUP Workshop Series, TAUP 2005, was organized by the University of Zaragoza and Laboratorio Subterráneo de Canfranc, jointly with the Laboratori Nazionali del Gran Sasso of the Italian Institute of Nuclear Physics (INFN). It was dedicated to the memory of professor Angel Morales, co-founder of the TAUP Series and a central figure in the scientific shaping and organization of the TAUP conferences since their inception in 1989. He and his group of collaborators laid, twenty years ago, the foundations of underground physics in Spain. To have TAUP 2005 hosted by the University of Zaragoza was a tangible way of honouring his memory. The Conference was concluded by a visit to the new installations of the Canfranc Laboratory, where a memorial ceremony was held in honour of Angel Morales, the driving force for the creation of that Laboratory. In TAUP 2005 all the various aspects of Astroparticle Physics have been covered, from Cosmology and Dark Constituents, to Gravitational Waves, to Neutrino Physics and Astrophysics, to High Energy Astrophysics, to Cosmic Rays and Gamma-Rays Astronomy. New and important scientific results were presented and debated in the plenary review talks and in a very large number of contributions in topical parallel sessions. As editors of these proceedings, we hope that this volume, which contains most of the talks and contributions presented at TAUP 2005, will provide a detailed state-of-the-art account of the various facets of Astroparticle Physics. We thank all the invited speakers and contributors who made this possible. Full coverage of the transparencies presented at the conference can be found on the website http://www.unizar.es/taup2005. At TAUP 2005 a memorial lecture was delivered by Art McDonald to commemorate John Bahcall, who passed away prematurely in August 2005. In this talk, his figure, as a pioneer and leader in the fields of Neutrino Physics, Astronomy and Astrophysics and as a man of great personal

  15. PREFACE: XIV International Conference on Calorimetry in High Energy Physics

    NASA Astrophysics Data System (ADS)

    Wang, Yifang

    2011-03-01

    The International Conferences on Calorimetry in High Energy Physics (also known as the Calor Conference series, started in October 1990 at Fermilab) address all aspects of calorimetric particle detection and measurement, with an emphasis on high energy physics experiments. The XIV International Conference on Calorimetry in High Energy Physics (Calor 2010) was held at the campus of the Institute of High Energy Physics, Beijing, China, from May 10-14, 2010. This conference brought together more than 110 participants from 20 countries, including senior scientists and young physicists. During the five days of the conference, 98 presentations were given in seven plenary sessions. The attendees had in-depth discussions on the latest developments and innovations in calorimetry, including the exciting new LHC results. From the presentations, 83 papers were published in this proceedings. The success of the conference was due to the participants' enthusiasm and the excellent talks given by the speakers, and to the conveners for organizing the individual sessions. We would like to thank the International Advisory Committee for giving us the opportunity to host this Conference in Beijing. Finally we would like to thank all the people involved in the organization of the Conference, who have provided valuable local support. Yifang WangChair of Local Organizing Committee International Advisory Committee M DanilovITEP Moscow M DiemozINFN Roma I A EreditatoBern F L FabbriINFN Frascati T KobayashiICEPP Tokyo M LivanPavia University & INFN P LubranoINFN Perugia S MagillANL Argonne A MaioLIPP Lisbon H OberlackMPI Munich A ParaFermilab R WigmansTTU Lubbock R YoshidaANL Argonne R ZhuCaltech Local Organizing Committee Y WangIHEP (Chair) Y GaoTshinghua University T HuIHEP (Scientific secretary) C LiUSTC W LiIHEP J LuIHEP P WangIHEP T XuIHEP L ZhouIHEP Session Conveners 1) Materials and detectors - Junguang Lu (IHEP), Francesca Nessi (CERN) 2) Algorithm and simulation - Nural Akchurin

  16. Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest

    NASA Technical Reports Server (NTRS)

    Vernikos, J.; Dallman, M. F.; Keil, L. C.; O'Hara, D.; Convertino, V. A.

    1993-01-01

    Endocrine regulation of fluids and electrolytes during 7 days of -6 degrees head-down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 h before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na(+)-to-K+ ratio and significant Na+ retention on re-ambulation. After the 1st day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone (Aldo), plasma volume was decreased, and the renal response to Aldo appeared to be appropriate. Circulating levels of arginine vasopressin, cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of early morning ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 days of HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after HDBR revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing before and after HDBR. Females had greater PRA and Aldo responses to standing before HDBR and larger Aldo responses to standing after HDBR than males.(ABSTRACT TRUNCATED AT 250 WORDS).

  17. Gender differences in endocrine responses to posture and 7 days of -6 degrees head-down bed rest.

    PubMed

    Vernikos, J; Dallman, M F; Keil, L C; O'Hara, D; Convertino, V A

    1993-07-01

    Endocrine regulation of fluids and electrolytes during 7 days of -6 degrees head-down bed rest (HDBR) was compared in male (n = 8) and, for the first time, female (n = 8) volunteers. The subjects' responses to quiet standing for 2 h before and after HDBR were also tested. In both sexes, diuresis and natriuresis were evident during the first 2-3 days of HDBR, resulting in a marked increase in the urinary Na(+)-to-K+ ratio and significant Na+ retention on re-ambulation. After the 1st day of HDBR, plasma renin activity (PRA) was increased relative to aldosterone (Aldo), plasma volume was decreased, and the renal response to Aldo appeared to be appropriate. Circulating levels of arginine vasopressin, cortisol, and ACTH were unchanged during HDBR. Plasma testosterone decreased slightly on day 2 of HDBR in males. The ratio of early morning ACTH to cortisol was lower in females than in males because ACTH was lower in females. Urinary cortisol increased and remained elevated throughout the HDBR in males only. There were no gender differences in the responses to 7 days of HDBR, except those in the pituitary-adrenal system; those differences appeared unrelated to the postural change. The provocative cardiovascular test of quiet standing before and after HDBR revealed both sex differences and effects of HDBR. There were significant sex differences in cardiovascular responses to standing before and after HDBR. Females had greater PRA and Aldo responses to standing before HDBR and larger Aldo responses to standing after HDBR than males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8338147

  18. Networked alpha and gamma spectral acquisition and analysis system

    SciTech Connect

    Wilcox, C.M.; Gross, J.M.

    1993-10-01

    This manual assumes a knowledge of (terminology used and a working familiarity with) the windowing system and mouse of the Sun computer workstation. See the appropriate Sun manuals for additional information. ALDO, the alpha detector control program, is used to control, monitor, and edit log information associated with the collection of alpha spectra. Actual data collection and control functions are performed by Mizar Real-Time computers for which ALDO acts as a friendly user command interface and status display. It is normally started as part of your login procedure, but may also be started from the ``NETSPEC Utilities`` submenu of the root menu. The root menu is obtained by pushing the right mouse button when the cursor is over the root window (background picture). To become a user of ALDO and the other programs in the NETSPEC system, contact the person who performs systems administration tasks for the Sun computers. Most user interaction with ALDO is by means of mouse manipulation of screen items such as buttons, checkboxes, and sliders. The action of pushing the left mouse button when the cursor is over an item is called selecting that item. The left mouse button is therefore called the select button. The right mouse button is the menu button because a limited number of options may be displayed when that button is pressed when the cursor is over an item with a triangle (inverted delta). In this document, names of selectable items are printed in bold when they are first mentioned or when emphasis is helpful. In general, items which do not apply to the current context are either disabled or made invisible in order to prevent selection.

  19. Phenotype of proliferating cells stimulated during compensatory adrenal growth.

    PubMed

    Holzwarth, M A; Gomez-Sanchez, C E; Engeland, W C

    1996-11-01

    The phenotype of the proliferating cells during adrenocortical growth has remained controversial although glomerulosa, fasciculata and intermediate zone cells have all been considered possible candidates. This was due in part to the inability to identify specific adrenocortical cell types in comparing different types of growth. In the present studies, using immunocytochemical localization of cytochrome P450 aldosterone synthase (P450aldo) and cytochrome P450 11 beta-hydroxylase (P45011 beta) to identify adrenocortical cell phenotypes as well as Ki-67 to label proliferating cells, we have investigated the phenotype of the proliferating cells in the compensatory adrenal growth response to unilateral adrenalectomy. Between 24 and 96 hrs after unilateral adrenalectomy, most Ki-67(+) nuclei were found in the outermost region of the fasciculata, as defined by P45011 beta immunoreactive cells. Few Ki-67(+) nuclei were found in the glomerulosa, defined by P450aldo cells or in the z intermedia, identified by the absence of both P450aldo and P45011 beta. To test which cell type is activated by unilateral adrenalectomy, we altered the phenotypic configuration of the adrenal cortex; rats were placed on a low Na+ diet for three weeks, resulting in a marked expansion of the number of P450aldo(+) cells. An abundance of proliferating cells was identified primarily in the expanded glomerulosa, but not in the intermedia or fasciculata. In contrast, the proliferation associated with compensatory growth in these low Na+ rats, was localized primarily in the outer P45011 beta(+) zone. These findings suggest that the phenotype of the proliferating cell is specific to the growth promoting stimulus.

  20. Researchers warn of 'worrying imprudence' over cuts

    NASA Astrophysics Data System (ADS)

    Cartlidge, Edwin

    2012-08-01

    Italian physicists reacted with anger to proposed cuts to the country's research funding. Particularly hard hit would be the National Institute of Nuclear Physics (INFN), which has been slated to absorb nearly half of the €120m reduction in the research ministry's budget as outlined in a decree on 6 July.

  1. Windows beyond the Standard Model

    SciTech Connect

    Bernabei, R.

    2007-10-12

    DAMA is an observatory for rare processes at the Gran Sasso National Laboratory of the I.N.F.N. (LNGS). Here some arguments will be shortly summarised on the investigation on dark matter (DM) particles by annual modulation signature and on some of the performed searches for double beta decay modes.

  2. The TRASCO Project

    NASA Astrophysics Data System (ADS)

    Pagani, Carlo

    2002-12-01

    TRASCO is a joint INFN/ENEA program, started in 1998, aiming at the design and the technological investigation of the main components of an accelerator driven system (ADS) for nuclear waste transmutation. The proposed 30 mA, 1 GeV, proton linac (TRASCO-AC) is briefly outlined, together with the ongoing R&D work on several key components.

  3. On the stability of a stringy black hole

    NASA Astrophysics Data System (ADS)

    Carlini, A.; Fucito, F.; Martellini, M.

    1992-09-01

    We study the stability under perturbations of a charged four-dimensional stringy black hole arising from gauging a previously studied WZW model. We find that the black hole is stable only in extremal case Q=M. Permanent address: Dipartimento di Fisica, Università di Milano, I-20133 Milan, Italy and INFN, Sezione di Pavia, Via Bassi 6, I-27100 Pavia, Italy.

  4. Hormonal changes after supine posture, immersion, and swimming.

    PubMed

    Viti, A; Lupo, C; Lodi, L; Bonifazi, M; Martelli, G

    1989-12-01

    This study was undertaken to evaluate the effects of the supine posture, immersion, and swimming on hormones involved in the regulation of hydrosaline equilibrium. Plasma levels of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA), and aldosterone (ALDO) were measured by radioimmunoassay in eight untrained young subjects (five males and three females). Blood samples were collected on different days: control morning samples in a relaxed standing posture before each test; after 20 min in a supine position; after 20 min of horizontal immersion in water at 28 degrees C; after 20 min of backstroke swimming (speed about 1 m/s). No changes occurred in AVP levels after each test. ALDO and PRA increased significantly only after swimming and were directly correlated. ANP increased significantly after immersion, but no further increase was observed after swimming. The hematocrit, which increased after swimming, was inversely correlated with ANP levels in the post-exercise samples. These data show that while ALDO and PRA increase only in response to swimming, even at moderate intensity, ANP probably requires more prolonged and intense exercise to reach a significantly higher level than in immersion. PMID:2534120

  5. PREFACE: Tenth International Conference on Topics in Astroparticle and Underground Physics (TAUP2007)

    NASA Astrophysics Data System (ADS)

    Inoue, Kunio; Suzuki, Atsuto; Mitsui, Tadao

    2008-07-01

    Otsuka, and Ms Yuri Endo, our workshop secretaries, for their continuous and excellent work in the organization of the conference, and to Ms Chiyo Itoh, and Ms Machiko Mizutani, for their invaluable assistance during the conference. We also gratefully thank the technical staff: Tomoaki Takayama, Hiromitsu Hanada, Takashi Nakajima, for their invaluable help. As announced at the end of the conference, TAUP 2009 will be held in Gran Sasso, Italy, hosted by the Istituto Nazionale di Fisica Nucleare (INFN) with the chair of Professor Eugenio Coccia. Kunio Inoue, Atsuto Suzuki and Tadao Mitsui COMMITTEES TAUP Steering Committee F T Avignone U South Carolina B C Barish CALTECH E Bellotti U Milano/INFN J Bernabéu U Valencia A Bottino (chair) U Torino/INFN V de Alfaro U Torino/INFN T Kajita ICRR U Tokyo C W Kim Johns Hopkins Univ /KIAS E Lorenz U München V Matveev INR Moskow J Morales U Zaragoza D Sinclair U Carleton M Spiro IN2P3 TAUP 2007 International Advisory Committee J J Aubert CNRS Marseille M Baldo-Ceolin U Padova/INFN V Berezinsky INFN-LNGS/INR L Bergström U Stockholm R Bernabei U Roma Tor Vergata/INFN A Bettini U Padova/INFN S Bilenky JINR Dubna D O Caldwell U C Santa Barbara E Coccia INFN-LNGS/U Roma Tor Vergata J Cronin U Chicago A Dar Technion Haifa G Domogatsky INR Moscow H Ejiri U Osaka J Ellis CERN E Fernández IFAE Barcelona E Fiorini U Milano/INFN G Fogli U Bari/INFN T Gaisser U Delaware G Gelmini UCLA G Gerbier CEA Saclay F Halzen U Wisconsin W Haxton U Washington T Kirsten MPI Heidelberg L Maiani U Roma/INFN A McDonald Queen's U K Nakamura KEK E Peterson U Minneapolis R Petronzio INFN/U Roma Tor Vergata G Raffelt MPI München R Rebolo IAC Tenerife L Resvanis U Athens P Salati U Savoie/LAPTH Annecy A Smirnov ICTP Trieste N Spooner U Sheffield S Ting MIT/CERN Y Totsuka U Tokyo M S Turner FNAL/U Chicago J W F Valle IFIC Valencia D Vignaud APC Paris F von Feilitzsch T U München G Zatsepin INR Moscow TAUP 2007 Organizing Committee A Bottino U Torino/INFN D

  6. Environmental radioactivity monitoring at the deep undeground Gran Sasso National Laboratory, Italy

    NASA Astrophysics Data System (ADS)

    Plastino, W.; Povinec, P. P.

    2009-12-01

    The neutron flux background plays a key-role in several research activities for Neutrino Physics and Dark Matter detection in underground environment. The neutron sources considered at deep underground are (α,n) reactions on light elements (e.g., Li, F, Na, etc.), spontaneous fission, mainly of 238U, and those induced by cosmic ray muons. The Gran Sasso National Laboratory—National Institute of Nuclear Physics (LNGS-INFN) is located inside the largest aquifer of central Italy. The natural radioactivity in rock and materials used for the internal structures of the LNGS-INFN has been studied in detail, and the specific activities of natural radionuclides are known with high accuracy for the characterization of neutron background at the LNGS-INFN. Moreover, numerical simulations and neutron flux measurements were carried out inside the LNGS-INFN. Nevertheless, the contribution of the natural radioactivity in the ground water and its spatial-temporal variations induced by the water-rock interaction and the hydrological properties of the Gran Sasso aquifer have never been considered. Within the framework of the INFN scientific program ERMES (Environmental Radioactivity Monitoring for Earth Sciences) environmental radioactivity measurements were performed inside the LNGS-INFN: particularly, radon [1, 2], radiocarbon [3], tritium [4], and new detectors independent of environmental noise parameters such as temperature, acid concentrations, humidity, and air pressure were tested [5]. These measurements have shown the existence of different chemical-physical and fluid dynamical characteristics in the ground water. The results of the ground water radioactivity monitoring show temporal modulations induced by ground water variations due to percolation effect related to snow melting, rainfall and/or diffusive processes through the structural discontinuities [6]. Furthermore, monitoring of chemical and physical groundwater parameters has been carried out worldwide in

  7. NUMEN Project @ LNS : Heavy Ions Double Charge Exchange as a tool towards the 0νββ Nuclear Matrix Element

    NASA Astrophysics Data System (ADS)

    Agodi, C.; Cappuzzello, F.; Bonanno, D. L.; Bongiovanni, D. G.; Branchina, V.; Calabrese, S.; Calabretta, L.; Calanna, A.; Carbone, D.; Cavallaro, M.; Colonna, M.; Foti, A.; Finocchiaro, P.; Greco, V.; Lanzalone, G.; Lo Presti, D.; Longhitano, F.; Muoio, A.; Pandola, L.; Rifuggiato, D.; Tudisco, S.

    2016-06-01

    The NUMEN Project, proposed at INFN Laboratori Nazionali del Sud (LNS) in Catania, has the aim to access the nuclear matrix elements, entering the expression of the life time of double beta decay, by relevant cross sections of double charge exchange reactions. The basic point, on which it is based this innovative technique, is the coincidence of the initial and final state wave-functions in the two classes of processes and the similarity of the transition operators. A key aspect of the Project is the use of MAGNEX large acceptance magnetic spectrometer, for the detection of the ejectiles, and of the INFN LNS K800 Superconducting Cyclotron (CS), for the acceleration of the required high resolution and low emittance heavy-ion beams.

  8. ``Galileo Galilei'' (GG) a small satellite to test the equivalence principle of Galileo, Newton and Einstein

    NASA Astrophysics Data System (ADS)

    Nobili, Anna M.; Comandi, Gian Luca; Doravari, Suresh; Bramanti, Donato; Kumar, Rajeev; Maccarrone, Francesco; Polacco, Erseo; Turyshev, Slava G.; Shao, Michael; Lipa, John; Dittus, Hansjoerg; Laemmerzhal, Claus; Peters, Achim; Mueller, Jurgen; Unnikrishnan, C. S.; Roxburgh, Ian W.; Brillet, Alain; Marchal, Christian; Luo, Jun; van der Ha, Jozef; Milyukov, Vadim; Iafolla, Valerio; Lucchesi, David; Tortora, Paolo; de Bernardis, Paolo; Palmonari, Federico; Focardi, Sergio; Zanello, Dino; Monaco, Salvatore; Mengali, Giovanni; Anselmo, Luciano; Iorio, Lorenzo; Knezevic, Zoran

    2009-03-01

    “Galileo Galilei” (GG) is a small satellite designed to fly in low Earth orbit with the goal of testing the Equivalence Principle—which is at the basis of the General Theory of Relativity—to 1 part in 1017. If successful, it would improve current laboratory results by 4 orders of magnitude. A confirmation would strongly constrain theories; proof of violation is believed to lead to a scientific revolution. The experiment design allows it to be carried out at ambient temperature inside a small 1-axis stabilized satellite (250 kg total mass). GG is under investigation at Phase A-2 level by ASI (Agenzia Spaziale Italiana) at Thales Alenia Space in Torino, while a laboratory prototype (known as GGG) is operational at INFN laboratories in Pisa, supported by INFN (Istituto Nazionale di fisica Nucleare) and ASI. A final study report will be published in 2009.

  9. Determination of the half-life of 213Fr with high precision

    NASA Astrophysics Data System (ADS)

    Fisichella, M.; Musumarra, A.; Farinon, F.; Nociforo, C.; Del Zoppo, A.; Figuera, P.; La Cognata, M.; Pellegriti, M. G.; Scuderi, V.; Torresi, D.; Strano, E.

    2013-07-01

    High-precision measurement of half-life and Qα value of neutral and highly charged α emitters is a major subject of investigation currently. In this framework, we recently pushed half-life measurements of neutral emitters to a precision of a few per mil. This result was achieved by using different techniques and apparatuses at Istituto Nazionale di Fisica Nucleare Laboratori Nazionali del Sud (INFN-LNS) and GSI Darmstadt. Here we report on 213Fr half-life determination [T1/2(213Fr) = 34.14±0.06 s] at INFN-LNS, detailing the measurement protocol used. Direct comparison with the accepted value in the literature shows a discrepancy of more than three sigma. We propose this new value as a reference, discussing previous experiments.

  10. Status of the SPARC Project

    SciTech Connect

    Alesini, D.; Bertolucci, S.; Bellaveglia, M.; Biagini, M.E.; Boni, R.; Boscolo, M.; Castellano, M.; Clozza, A.; Pirro, G.Di; Drago, A.; Esposito, A.; Ferrario, M.; Ficcadenti, L.; Filippetto, D.; Fusco, V.; Gallo, A.; Gatti, G.; Ghigo, A.; Guiducci, S.; Incurvati, M.; Ligi, C.; /Frascati /INFN, Milan /Milan U. /INFN, Rome /INFN, Rome /ENEA, Frascati /Milan, Polytechnic /UCLA /SLAC

    2006-01-25

    The SPARC project has entered its installation phase at the Frascati National Laboratories of INFN: its main goal, the promotion of an R&D activity oriented to the development of a high brightness photoinjector to drive SASE-FEL experiments, is being vigorously pursued by a collaboration among ENEA-INFN-CNR-Universita di Roma Tor Vergata-INFM-ST. In this paper we will report on the installation and test of some major components, like Ti:Sa laser system, RF gun and RF power system. Advancements in the control and beam diagnostics systems will also be reported, in particular on the emittance-meter device for beam emittance measurements in the drift space downstream the RF gun. Recent results on laser pulse shaping show the feasibility of producing 10 ps flat-top laser pulses in the UV with rise time below 1 ps. First FEL experiments have been proposed, using SASE, seeding and non-linear resonant harmonics.

  11. The Gamma Ray Imaging Detector of the AGILE satellite: A novel application of silicon trackers for detection of astrophysics high-energy photons

    NASA Astrophysics Data System (ADS)

    Rappoldi, Andrea; AGILE Collaboration

    2009-10-01

    AGILE is a project of the Italian Space Agency (ASI) Scientific Program dedicated to Gamma ray astrophysics. It is designed to be a very light and compact instrument, capable of photon detections and imaging in both the 30 MeV-50 GeV and 18-60 keV energy ranges, with a large field of view (FOV is ˜3 and ˜1 sr, respectively). The core of the instrument (launched on April 23, 2007 from the Indian Space Research Organization's launch facility) is represented by the Gamma Ray Imaging Detector (GRID), which is a silicon tracker developed by the Italian National Institute of Nuclear Physics (INFN), with a spatial resolution of ˜40 μm. The GRID performances have been studied by means of a GEANT Montecarlo, and tested with a dedicated calibration campaign using the tagged gamma beam available at Beam Test Facility (BTF) of INFN Frascati Laboratory.

  12. PREFACE: Young Researcher Meeting in Rome 2012

    NASA Astrophysics Data System (ADS)

    Agostini, Fabio; Cattani, Giordano; Mazzaferro, Luca; Migliaccio, Marina; Pietrobon, Davide; Ricci Pacifici, Daniel; Stellato, Francesco; Veneziani, Marcella

    2012-10-01

    Conference logo At its third edition, the Young Researcher Meeting in Rome (YRMR) proves to be a growing event in the Italian scientific panorama. The high-quality content of the abstracts submitted to the scientific committee resulted in an exciting conference, held, for the second time, at the University of Rome 'Tor Vergata' on 20 January 2012. A busy schedule covered a large variety of cutting-edge science topics: fundamental interactions, particle physics, cosmology, astrophysics, condensed matter and biomedical physics. The broad range of the subjects discussed is the distinctive feature of the YRMR, a meeting aimed at enhancing the synergy among complementary branches of science by stimulating a fruitful exchange between theoretical, experimental and computational physics. Promoting collaborations between PhD students, postdoctoral fellows and young researchers creates a solid scientific network with an open-minded approach to discovery. In this volume, we collect the contributions that have been presented both in the form of talks and of posters. YRMR Organising and Editorial Committee Fabio Agostini (fabio.agostini@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Giordano Cattani (giordano.cattani@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' INFN sezione di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Luca Mazzaferro (luca.mazzaferro@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' INFN sezione di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma Italy Marina Migliaccio (migliaccio@ifca.unican.es) Instituto de Fisica de Cantabria, Edificio Juan Jorda, Avenida de los Castros, E-39005 Santander, Cantabria Spain Davide Pietrobon (davide.pietrobon@jpl.nasa.gov) Jet Propulsion Laboratory - California Institute of Technology 4800 Oak Grove Drive 169-237 91109 Pasadena, CA USA Daniel Ricci Pacifici

  13. PRESS-MAG-O: a unique instrument to probe materials and phenomena under extreme conditions at Frascati

    NASA Astrophysics Data System (ADS)

    Di Gioacchino, Daniele; Marcelli, Augusto; Cestelli Guidi, Mariangela; Puri, Alessandro; Postorino, Paolo; Pace, Emanuele; De Sio, Antonio; Gambicorti, Lisa

    2011-03-01

    PRESS-MAG-O is a new instrument under commission at the Laboratori Nazionali di Frascati of the Istituto Nazionale di Fisica Nucleare (INFN) designed to investigate materials under extreme conditions. The instrument, once completed, will allow combining high harmonic AC magnetic susceptibility measurements and magneto-optic experiments on samples under high pressures (HP), with a variable DC magnetic field in a wide temperature range. The system is designed to work at SINBAD, the IR synchrotron radiation beamline operational since 2001 at DAΦNE (Double AnnularΦ-factory for Nice Experiments), the storage ring of the Laboratori Nazionali di Frascati of the INFN. HP will be applied up to about 20 GPa to samples inside a Cu-Be diamond anvil cell designed to allow concurrent FTIR experiments and high harmonic AC susceptibility measurements in a DC magnetic field up to 8 T and in a wide temperature range.

  14. COMMITTEES: Proceedings of the 13th Gravitational Waves Data Analysis Workshop (GWDAW13), San Juan, Puerto Rico, 19-22 January 2009 Proceedings of the 13th Gravitational Waves Data Analysis Workshop (GWDAW13), San Juan, Puerto Rico, 19-22 January 2009

    NASA Astrophysics Data System (ADS)

    2009-10-01

    Science Organising Committee (SOC) Bruce Allen, AEI, Germany Patrick Brady, University of Wisconsin Milwaukee, USA Deepto Chakrabarty, MIT, USA Eugenio Coccia, INFN, Gran Sasso, Italy James Cordes, Cornell University, USA Mario Díaz (Chair), University of Texas Brownsville, USA Sam Finn, Penn State, USA Neil Gehrels, NASA GSFC, USA Fredrick A Jenet, University of Texas Brownsville, USA Nobuyuki Kanda, Osaka City University, Japan Erik Katsavounides, MIT, USA Dick Manchester, ATNF, Australia Soumya Mohanty, University of Texas Brownsville, USA Benoit Mours, LAPP-Annecy, France Maria Alessandra Papa, AEI, Germany Kate Scholberg, Duke University, USA Susan Scott, The Australian National University Alberto Vecchio, University of Birmingham, UK Andrea Vicere, INFN - Sezione di Firenze, Italy Stan Whitcomb, LIGO CALTECH, USA Local Organising Committee (LOC) Paulo Freire (Arecibo Observatory, Puerto Rico) Murray Lewis (Arecibo Observatory, Puerto Rico) Wanda Wiley (University of Texas Brownsville, USA)

  15. Improvement of beam emittance of the CEA high intensity proton source SILHI

    NASA Astrophysics Data System (ADS)

    Gobin, R.; Beauvais, P.-Y.; Ferdinand, R.; Leroy, P.-A.; Celona, L.; Ciavola, G.; Gammino, S.

    1999-06-01

    The emittance of the intense proton beam extracted by the source SILHI at Commisariat à l'Energie Atomique (CEA)-Saclay is a key parameter for the design of the IPHI Project RFQ. This parameter has a relevant role even for the design of an intense proton source for the TRASCO project of Istituto Nazionale di Fisica Nucleare (INFN). The tests performed in the framework of CEA-INFN collaboration have been mainly devoted to a 75 mA beam emittance investigation injecting different gases in the beam line. The results show that the rms normalized emittance decreases up to a factor 3 while the beam losses induced by recombination are contained within 5%. Normalized emittance in r-r' plane of about 0.1 π min mrad have been obtained using Ar and Kr.

  16. On-line remote monitoring of radioactive waste repositories

    NASA Astrophysics Data System (ADS)

    Calì, Claudio; Cosentino, Luigi; Litrico, Pietro; Pappalardo, Alfio; Scirè, Carlotta; Scirè, Sergio; Vecchio, Gianfranco; Finocchiaro, Paolo; Alfieri, Severino; Mariani, Annamaria

    2014-12-01

    A low-cost array of modular sensors for online monitoring of radioactive waste was developed at INFN-LNS. We implemented a new kind of gamma counter, based on Silicon PhotoMultipliers and scintillating fibers, that behaves like a cheap scintillating Geiger-Muller counter. It can be placed in shape of a fine grid around each single waste drum in a repository. Front-end electronics and an FPGA-based counting system were developed to handle the field data, also implementing data transmission, a graphical user interface and a data storage system. A test of four sensors in a real radwaste storage site was performed with promising results. Following the tests an agreement was signed between INFN and Sogin for the joint development and installation of a prototype DMNR (Detector Mesh for Nuclear Repository) system inside the Garigliano radwaste repository in Sessa Aurunca (CE, Italy). Such a development is currently under way, with the installation foreseen within 2014.

  17. Study of silicon photomultipliers fast amplifier and thermoregulation

    NASA Astrophysics Data System (ADS)

    D'Antone, I.; Fabbri, L.; Foschi, E.; Guandalini, C.; Laurenti, G.; Lax, I.; Levi, G.; Quadrani, L.; Sbarra, Ca.; Sbarra, Cr.; Villa, M.; Zoccoli, A.; Zuffa, M.

    2011-02-01

    The silicon photomultipliers (SiPM) are adopted in various physical applications, from medical physics to astrophysics, for their advantages in terms of cost and weight with respect to traditional photo detectors. Their low bias voltage supply (about 30 V), hardiness and resistance to magnetic field are ideal characteristics for space application. In the frame of INFN-Irst collaboration, some of them have been developed and produced at FBK (Trento-Italy), and have been characterized in the INFN laboratories of Bologna (DaSiPM2 collaboration). The SiPM can be used in conjunction with fibres and counters in high energy physics experiments. To exploit the SiPM time resolution, a fast amplifier has been studied. The SiPM gain depends critically on temperature and a thermal stabilization is also necessary. The use of a thermoelectric cooler module based on a Peltier cell has been investigated, and the results are shown.

  18. A magneto-optical trap for radioactive atoms

    NASA Astrophysics Data System (ADS)

    Mariotti, E.; Khanbekyan, K.; Marinelli, C.; Marmugi, L.; Moi, L.; Corradi, L.; Dainelli, A.; Calabrese, R.; Mazzocca, G.; Tomassetti, L.; Minguzzi, P.

    2013-03-01

    This paper presents the recent results of the TrapRad/Francium collaboration whose final aim is the measurement of the Atomic Parity Non-Conservation effect (APNC) in Francium atoms stored in a Magneto - Optical Trap (MOT) built at the Laboratori Nazionali di Legnaro (LNL) of the National Institute for Nuclear Physics (INFN). Current developments and new strategies to enhance the trapping efficiency of Francium isotopes and to detect new spectroscopic features are reported.

  19. Explodet Project:. Methods of Automatic Data Processing and Analysis for the Detection of Hidden Explosive

    NASA Astrophysics Data System (ADS)

    Lecca, Paola

    2003-12-01

    The research of the INFN Gruppo Collegato di Trento in the ambit of EXPLODET project for the humanitarian demining, is devoted to the development of a software procedure for the automatization of data analysis and decision taking about the presence of hidden explosive. Innovative algorithms of likely background calculation, a system based on neural networks for energy calibration and simple statistical methods for the qualitative consistency check of the signals are the main parts of the software performing the automatic data elaboration.

  20. Inequalities on the Overshoot beyond a Boundary for Independent Summands with Differing Distributions

    PubMed Central

    Spouge, John L.

    2007-01-01

    Let {Sn : n ≥ 0} (S0 = 0) denote the successive sums of independent non-negative random variates, of possibly differing distributions. Define: (1) the number N(b) = inf{n ≥ 0 : Sn > b} of sums in the interval [0,b]; and (2) the overshoot Rb = SN(b) −b. This paper bounds the tail ℙ{Rb > c} and the moments 𝔼Rbk. PMID:19461943

  1. PArthENoPE: Public Algorithm Evaluating the Nucleosynthesis of Primordial Elements

    SciTech Connect

    Pisanti, O.; Cirillo, A.; Esposito, S.; Iocco, F.; Mangano, G.; Miele, G.; Serpico, P.D.

    2007-05-04

    We describe a program for computing the abundances of light elements produced during Big Bang Nucleosynthesis which is publicly available at http://parthenope.na.infn.it/. Starting from nuclear statistical equilibrium conditions the program solves the set of coupled ordinary differential equations, follows the departure from chemical equilibrium of nuclear species, and determines their asymptotic abundances as function of several input cosmological parameters as the baryon density, the number of effective neutrino, the value of cosmological constant and the neutrino chemical potential.

  2. The AMY experiment: Microwave emission from air shower plasmas

    NASA Astrophysics Data System (ADS)

    Alvarez-Muñiz, J.; Blanco, M.; Boháčová, M.; Buonomo, B.; Cataldi, G.; Coluccia, M. R.; Creti, P.; De Mitri, I.; Di Giulio, C.; Facal San Luis, P.; Foggetta, L.; Gaïor, R.; Garcia-Fernandez, D.; Iarlori, M.; Le Coz, S.; Letessier-Selvon, A.; Louedec, K.; Maris, I. C.; Martello, D.; Mazzitelli, G.; Monasor, M.; Perrone, L.; Petrera, S.; Privitera, P.; Rizi, V.; Rodriguez Fernandez, G.; Salamida, F.; Salina, G.; Settimo, M.; Valente, P.; Vazquez, J. R.; Verzi, V.; Williams, C.

    2016-07-01

    You The Air Microwave Yield (AMY) experiment investigate the molecular bremsstrahlung radiation emitted in the GHz frequency range from an electron beam induced air-shower. The measurements have been performed at the Beam Test Facility (BTF) of Frascati INFN National Laboratories with a 510 MeV electron beam in a wide frequency range between 1 and 20 GHz. We present the apparatus and the results of the tests performed.

  3. RIB Production at LNL: the EXOTIC Facility

    NASA Astrophysics Data System (ADS)

    Marco, Mazzocco

    2016-04-01

    Nuclear reactions involving radioactive isotopes are extremely relevant in several astrophysical scenarios, from the Big-Bang Nucleosynthesis to Supernovae explosions. In this contribution the production of Radioactive Ion Beams (RIBs) by means of the in-flight technique is reviewed. In particular, the use of direct reactions in inverse kinematics for the production of light weakly-bound RIBs by means of the facility EXOTIC at INFN-LNL (Italy) will be described in detail.

  4. Modern Detectors for Astroparticle Physics

    SciTech Connect

    Adriani, Oscar

    2005-10-12

    This paper focus on the necessary requirements for a modern astroparticle physics detector based either on stratospheric balloons, either on satellite. The main technical solutions used to build a reliable detector are described. Finally, the most relevant experiments that have been developed with the INFN contribution and that will be ready in the near future (both for {gamma} and charged cosmic rays detection) are described.

  5. RF tests of the beta - 0.5 five cell TRASCO cavities

    SciTech Connect

    A. Bosotti; Carlo Pagani; P. Pierini; J.P. Charrier; B. Visentin; Gianluigi Ciovati; Peter Kneisel

    2004-07-01

    Two complete 5 cell superconducting cavities at {beta} = 0.5 have been fabricated in the TRASCO INFN program. The cavities have been designed to minimize peak electric and magnetic fields, with a goal of 8.5 MV/m of accelerating gradient, at a Q > 5 10{sup 9}. The cavities have been tested in vertical cryostats at TJNAF and Saclay and the results are summarized here.

  6. The SPARX Project: R & D Activity Towards X-Rays FEL Sources

    SciTech Connect

    Alesini, D.; Bellaveglia, M.; Bertolucci, S.; Biagini, M.E.; Boni, R.; Boscolo, M.; Castellano, M.; Clozza, A.; Di Pirro, G.; Drago, A.; Esposito, A.; Ferrario, M.; Filippetto, D.; Fusco, V.; Gallo, A.; Ghigo, A.; Guiducci, S.; Incurvati, M.; Ligi, C.; Marcellini, F.; Migliorati, M.; /Frascati /ENEA, Frascati /INFN, Milan /INFN, Rome /INFN, Rome2 /Milan Polytechnic /UCLA /SLAC

    2005-08-05

    SPARX is an evolutionary project proposed by a collaboration among ENEA-INFN-CNR-Universita di Roma Tor Vergata aiming at the construction of a FELSASE X-ray source in the Tor Vergata Campus. The first phase of the SPARX project, funded by Government Agencies, will be focused on R&D activity on critical components and techniques for future X-ray facilities as described in this paper.

  7. The fiber-SiPMT beam monitor of the R484 experiment at the RIKEN-RAL muon facility

    NASA Astrophysics Data System (ADS)

    Carbone, R.; Bonesini, M.; Bertoni, R.; Mazza, R.; Rossella, M.; Tortora, L.; Vacchi, A.; Vallazza, E.; Zampa, G.

    2015-03-01

    The scintillating fibers SiPM based beam monitor detector, designed to deliver position, shape and timing of the low energy muon beam at the RIKEN-RAL muon facility for the R484 experiment, has been successfully tested on the electron beam at the Beam Test Facility (BTF) of the INFN LNF laboratories. We report here the lay out and the read out structure as well as the very promising results.

  8. Planckian vertices on high genus Riemann surfaces

    NASA Astrophysics Data System (ADS)

    Bellini, Alessandro

    1993-04-01

    We suggest a method to compute subleading contributions at planckian energies for superstring scattering amplitudes of any genus. In particular, we test the method at one-loop level by comparison with previous results for the Regge trajectory renormalization. Modular invariance of these asymptotic terms is also discussed. Permanent address: Dipartimento di Fisica dell'Università, Firenze and INFN, Sezione di Firenze, Largo E. Fermi 2, I-50125 Florence, Italy.

  9. Aldolase-B knockout in mice phenocopies hereditary fructose intolerance in humans.

    PubMed

    Oppelt, Sarah A; Sennott, Erin M; Tolan, Dean R

    2015-03-01

    The rise in fructose consumption, and its correlation with symptoms of metabolic syndrome (MBS), has highlighted the need for a better understanding of fructose metabolism. To that end, valid rodent models reflecting the same metabolism as in humans, both biochemically and physiologically, are critical. A key to understanding any type of metabolism comes from study of disease states that affect such metabolism. A serious defect of fructose metabolism is the autosomal recessive condition called hereditary fructose intolerance (HFI), caused by mutations in the human aldolase B gene (Aldob). Those afflicted with HFI experience liver and kidney dysfunction after fructose consumption, which can lead to death, particularly during infancy. With very low levels of fructose exposure, HFI patients develop non-alcoholic fatty acid liver disease and fibrosis, sharing liver pathologies also seen in MBS. A major step toward establishing that fructose metabolism in mice mimics that of humans is reported by investigating the consequences of targeting the mouse aldolase-B gene (Aldo2) for deletion in mice (Aldo2(-/-)). The Aldo2(-/-) homozygous mice show similar pathology following exposure to fructose as humans with HFI such as failure to thrive, liver dysfunction, and potential morbidity. Establishing that this mouse reflects the symptoms of HFI in humans is critical for comparison of rodent studies to the human condition, where this food source is increasing, and increasingly controversial. This animal should provide a valuable resource for answering remaining questions about fructose metabolism in HFI, as well as help investigate the biochemical mechanisms leading to liver pathologies seen in MBS from high fructose diets.

  10. Adaptation of aldosterone biosynthesis to sodium and potassium intake in the rat.

    PubMed

    Müller, J; Meuli, C; Schmid, C; Lauber, M

    1989-01-01

    The steroidogenic response of rat adrenal zona glomerulosa to stimulators is variable and depends on the activity of biosynthetic steps involved in the conversion of deoxycorticosterone (DOC) to aldosterone (Aldo). Corticosterone methyl oxidations (CMO) 1 and 2 are stimulated by sodium restriction and suppressed by potassium restriction. These slow alterations are accompanied by the appearance or disappearance of a specific zona glomerulosa mitochondrial protein with a molecular weight of 49,000. Induction of CMO 1 and 2 activities and the appearance of the 49 K protein can also be elicited in vitro by culture of rat zone glomerulosa cells in a medium with a high potassium concentration. The 49 K protein crossreacts with a monoclonal antibody raised against purified bovine adrenal cytochrome P-450(11 beta). The same antibody stains a protein with a molecular weight of 51,000 in rat zona fasciculata mitochondria and in zone glomerulosa mitochondria of rats in which CMO 1 and 2 activities have been suppressed by potassium restriction and sodium loading. The 51 K crossreactive protein was purified to electrophoretic homogeneity by chromatography on octyl-sepharose. In a reconstituted enzyme system, it converted DOC to corticosterone (B) and to 18-hydroxy-11-deoxycorticosterone (18-OH-DOC) but not to 18-hydroxycorticosterone (18-OH-B) or Aldo. A partially purified 49 K protein preparation from zona glomerulosa mitochondria of rats kept on a low-sodium, high-potassium regimen converted DOC to B, 18-OH-DOC, 18-OH-B and Aldo. According to these results, rat adrenal cytochrome P-450(11 beta) exists in two different forms, with both of them capable of hydroxylating DOC in either the 11 beta- of the 18-position, but with only the 49 K form capable of catalyzing CMO 1 and 2. The adaptation of aldosterone biosynthesis to sodium deficiency or potassium intake in rats is due to the appearance of the 49 K form of the enzyme in zona glomerulosa mitochondria.

  11. Plasma vasopressin, renin activity, and aldosterone responses to maximal exercise in active college females.

    PubMed

    Maresh, C M; Wang, B C; Goetz, K L

    1985-01-01

    The effect of maximal treadmill exercise on plasma concentrations of vasopressin (AVP); renin activity (PRA); and aldosterone (ALDO) was studied in nine female college basketball players before and after a 5-month basketball season. Pre-season plasma AVP increased (p less than 0.05) from a pre-exercise concentration of 3.8 +/- 0.5 to 15.8 +/- 4.8 pg X ml-1 following exercise. Post-season, the pre-exercise plasma AVP level averaged 1.5 +/- 0.5 pg X ml-1 and increased to 16.7 +/- 5.9 pg X ml-1 after the exercise test. PRA increased (p less than 0.05) from a pre-exercise value of 1.6 +/- 0.6 to 6.8 +/- 1.7 ngAI X ml-1 X hr-1 5 min after the end of exercise during the pre-season test. In the post-season, the pre-exercise PRA was comparable (2.4 +/- 0.6 ngAI X ml- X hr-1), as was the elevation found after maximal exercise (8.3 +/- 1.9 ngAI X ml- X hr-1). Pre-season plasma ALDO increased (p less than 0.05) from 102.9 +/- 30.8 pg X ml-1 in the pre-exercise period to 453.8 +/- 54.8 pg X ml-1 after the exercise test. In the post-season the values were 108.9 +/- 19.4 and 365.9 +/- 64.4 pg X ml-1, respectively. Thus, maximal exercise in females produced significant increases in plasma AVP, renin activity, and ALDO that are comparable to those reported previously for male subjects. Moreover, this response is remarkably reproducible as demonstrated by the results of the two tests performed 5 months apart.

  12. PREFACE: XIII International Conference on Calorimetry in High Energy Physics (CALOR 2008)

    NASA Astrophysics Data System (ADS)

    Livan, Michele

    2009-07-01

    presentations, now reported in these proceedings, that were debated in stimulating and fruitful discussions. Outside of the Workshop, the participants were able to visit the historical Halls and Museum of the University, whose foundation dates back to the year 1361, and to enjoy a visit to the Certosa, a Carthusian monastery renowned for its exuberant architecture. Pavia welcomed the Conference participants by opening the doors of the Town Hall and offering a reception during which the Mayor's address underlined the importance of research and its applications in modern society. The successful organization and the smooth running of the Conference is due to many people and Institutions. We gratefully acknowledge the financial support of the Istituto Nazionale di Fisica Nucleare (INFN), the Department of Nuclear and Theoretical Physics and the University of Pavia, that made the Workshop possible, together with the contribution of our sponsors. The University also opened some rooms of the Chancellor's suite for the lunch and coffee breaks, and hosted the Conference Secretariat. We would like to express our deepest gratitude to the INFN and Department technical staff, who helped to prepare the Hall for the Conference and to provide computer services, and to the staff of the Theresian Library, who gave us access to the Room and organized a display of the many historical books from their vast and precious collections which are of interest to physicists. Above all, the success of the meeting is due to the participants who animated it, and in particular to the speakers for their dedicated work in preparing their excellent talks and in providing the write-ups, and to the conveners for their essential role in shaping an interesting and well balanced scientific program. Finally, we wish to thank the International Advisory Committee for their unfailing support and for offering us the opportunity to organize this Conference in Pavia. Michele Livan Chairman, Organizing Committee International

  13. The GINGERino ring laser gyroscope, seismological observations at one year from the first light

    NASA Astrophysics Data System (ADS)

    Simonelli, Andreino; Belfi, Jacopo; Beverini, Nicolò; Di Virgilio, Angela; Carelli, Giorgio; Maccioni, Enrico; De Luca, Gaetano; Saccorotti, Gilberto

    2016-04-01

    The GINGERino ring laser gyroscope (RLG) is a new large observatory-class RLG located in Gran Sasso underground laboratory (LNGS), one national laboratory of the INFN (Istituto Nazionale di Fisica Nucleare). The GINGERino apparatus funded by INFN in the context of a larger project of fundamental physics is intended as a pathfinder instrument to reach the high sensitivity needed to observe general relativity effects; more details are found at the URL (https://web2.infn.it/GINGER/index.php/it/). The sensitivity reached by our instrument in the first year after the set up permitted us to acquire important seismological data of ground rotations during the transit of seismic waves generated by seisms at different epicentral distances. RLGs are in fact the best sensors for capturing the rotational motions associated with the transit of seismic waves, thanks to the optical measurement principle, these instruments are in fact insensitive to translations. Ground translations are recorded by two seismometers: a Nanometrics Trillium 240 s and Guralp CMG 3T 360 s, the first instrument is part of the national earthquake monitoring program of the Istituto Nazionale di Geofisica e Vulcanologia (INGV) and provides the ground translation data to be compared to the RLG rotational data. We report the waveforms and the seismological analysis of some seismic events recorded during our first year of activity inside the LNGS laboratory.

  14. 8th International Workshop on Top Quark Physics

    NASA Astrophysics Data System (ADS)

    2015-09-01

    The workshop will bring together the community of experimental and theoretical physicists working on top quark physics, 20 years after its first discovery, and at the beginning of the exploration of the new energy regime at the Large Hadron Collider. The workshop will provide a comprehensive overview of the latest results from the LHC and Tevatron experiments as well as the most recent theoretical developments and an outlook on top-quark physics at future colliders. The programme will consist of plenary presentations, a Poster Session, a Young Scientists Forum and 'Question and Answers' sessions, targeted for young researchers. A significant fraction of the workshop time will be devoted to discussions. The goal of the workshop is to provide a comprehensive picture of top-quark physics and a forum where experimentalists and theorists can discuss the interpretation of top quark results and plan future measurements. EDITORIAL BOARD: Luca Lista (INFN Naples), Fabrizio Margaroli (Univ. of Rome "La Sapienza") and Francesco Tramontano (Univ. of Naples "Federico II"). REFEREES: Luca Lista (INFN Naples), Fabrizio Margaroli (Univ. of Rome "La Sapienza"), Francesco Tramontano (Univ. of Naples "Federico II"), Francesco Fabozzi (Univ. of Basilicata), Alberto Orso Maria Iorio (Univ. of Naples "Federico II"), Antonello Davide Polosa (Univ. of Rome "La Sapienza") and Marco Rescigno (INFN Rome-I)

  15. Test of a coaxial blade tuner at HTS FNAL

    SciTech Connect

    Pischalnikov, Y.; Barbanotti, S.; Harms, E.; Hocker, A.; Khabiboulline, T.; Schappert, W.; Bosotti, A.; Pagani, C.; Paparella, R.; /LASA, Segrate

    2011-03-01

    A coaxial blade tuner has been selected for the 1.3GHz SRF cavities of the Fermilab SRF Accelerator Test Facility. Results from tuner cold tests in the Fermilab Horizontal Test Stand are presented. Fermilab is constructing the SRF Accelerator Test Facility, a facility for accelerator physics research and development. This facility will contain a total of six cryomodules, each containing eight 1.3 GHz nine-cell elliptical cavities. Each cavity will be equipped with a Slim Blade Tuner designed by INFN Milan. The blade tuner incorporates both a stepper motor and piezo actuators to allow for both slow and fast cavity tuning. The stepper motor allows the cavity frequency to be statically tuned over a range of 500 kHz with an accuracy of several Hz. The piezos provide up to 2 kHz of dynamic tuning for compensation of Lorentz force detuning and variations in the He bath pressure. The first eight blade tuners were built at INFN Milan, but the remainder are being manufactured commercially following the INFN design. To date, more than 40 of the commercial tuners have been delivered.

  16. Bifunctional building blocks in the Ugi-azide condensation reaction: A general strategy toward exploration of new molecular diversity†

    PubMed Central

    Gunawan, Steven; Hulme, Christopher

    2013-01-01

    1,5-disubstituted tetrazoles are an important drug-like scaffold known for their ability to mimic the cis-amide bond conformation. The scaffold is readily accessible via substitution of the carboxylic acid component of the Ugi multi-component reaction (MCR) with TMSN3 in what is herein denoted the Ugi-azide reaction. This full paper presents a concise, novel, general strategy to access a plethora of new heterocylic scaffolds utilizing tethered aldo/keto-acids/esters in the Ugi-azide reaction followed by a ring closing event that generates novel highly complex bis-heterocyclic lactam-tetrazoles. PMID:23912086

  17. [Subdural effusions in children. Pathophysiology and treatment].

    PubMed

    Gusmão, S; Silveira, R L; Cabral Filho, G; Arantes, A; Jermani, C

    1997-06-01

    Nine children harboring subdural effusions were treated by subduro peritoneal shunt. These patients were followed-up by CT scans. The area of the subdural effusions was measured by quantitative morphology with a planimeter. With the surgical treatment, the subdural effusion disappeared completely or near completely in 8 patients. The patient's functional state were excellent in 4, good in 3 and bad in 2 in the postoperative follow-up. We aldo reviewed the literature as far as the pathophysiology and the treatment of the subdural effusions are concerned.

  18. Self and other in communication and cognition: the role of auto-communication and intersubjectivity in autopoiesis of psychic systems.

    PubMed

    Märtsin, Mariann

    2008-06-01

    By referring to Niklas Luhmann's theory of self-referential systems, Aldo Mascareño (2008, submitted for publication) gives an account of system-environment interrelatedness, explaining how social and individual constitute each other through the process of communication and co-creation of meanings. Two possible extensions to his account are discussed. Firstly, auto-communication within the system that happens without any external reference needs to be taken into account while describing the existence and constant re-creation of psychic systems. Secondly, in order for the system and environment or two systems to communicate, an imagined and temporary intersubjectivity between the two needs to be assumed.

  19. Leopold Fellows meet

    NASA Astrophysics Data System (ADS)

    Hartmann, Dennis L.

    Communicating the results of environmental science research to nonscientists was the focus of a week-long meeting of fellows of the Aldo Leopold Leadership Program (ALLP) in June. Participating were 20 mid-career university facultymembers, the first group of ALLP fellows to be selected.Discussions were held on the role of scientists in society, techniques for effective leadership, improving communications skills, and working productively with news media. The training program considers both print and broadcast media as well as other outreach vehicles. The meeting was held at Kah Nee Ta Resort on the Warm Springs Indian Reservation, Warm Springs, Oregon, June 15-21, 1999.

  20. Common elements on the surface of glycolytic enzymes from Trypanosoma brucei may serve as topogenic signals for import into glycosomes.

    PubMed

    Wierenga, R K; Swinkels, B; Michels, P A; Osinga, K; Misset, O; Van Beeumen, J; Gibson, W C; Postma, J P; Borst, P; Opperdoes, F R

    1987-01-01

    In Trypanosoma brucei, a major pathogenic protozoan parasite of Central Africa, a number of glycolytic enzymes present in the cytosol of other organisms are uniquely segregated in a microbody-like organelle, the glycosome, which they are believed to reach post-translationally after being synthesized by free ribosomes in the cytosol. In a search for possible topogenic signals responsible for import into glycosomes we have compared the amino acid sequences of four glycosomal enzymes: triosephosphate isomerase (TIM), glyceraldehyde-phosphate dehydrogenase (GAPDH), phosphoglycerate kinase (PGK) and aldolase (ALDO), with each other and with their cytosolic counterparts. Each of these enzymes contains a marked excess of positive charges, distributed in two or more clusters along the polypeptide chain. Modelling of the three-dimensional structures of TIM, PGK and GAPDH using the known structural coordinates of homologous enzymes from other organisms indicates that all three may have in common two 'hot spots' about 40 A apart, which themselves include a pair of basic amino acid residues separated by a distance of about 7 A. The sequence of glycosomal ALDO, for which no three-dimensional information is available, is compatible with the presence of the same configuration on the surface of this enzyme. We propose that this feature plays an essential role in the import of enzymes into glycosomes.

  1. Effects of spironolactone on human blood mononuclear cells: mineralocorticoid receptor independent effects on gene expression and late apoptosis induction.

    PubMed

    Sønder, Søren Ulrik Salling; Mikkelsen, Marianne; Rieneck, Klaus; Hedegaard, Chris Juul; Bendtzen, Klaus

    2006-05-01

    1 Spironolactone (SPIR) binds to cytoplasmic mineralocorticoid receptors (MR) and functions as an aldosterone antagonist. Recently, the drug was shown to have an early suppressive effect on several immunoactive and proinflammatory cytokines. 2 To elucidate the mechanism behind this, the four MR-binding steroids SPIR, canrenone, 7alpha-thiomethyl-spironolactone and aldosterone (ALDO) were investigated for effects on lipopolysaccharide- and phytohemagglutinin-A-activated human blood mononuclear cells. Gene expression was examined after 4 h using microarrays, and SPIR affected 1018 transcripts of the (=) 22,000 probed. In contrast, the SPIR-related steroids affected 17 or fewer transcripts. Combining SPIR and ALDO resulted in 940 affected transcripts, indicating that SPIR has an early gene-regulatory effect independent of MR. 3 The affected genes encode a large number of signalling proteins and receptors, including immunoinflammatory response genes and apoptosis and antiapoptosis genes. Apoptosis was evident in CD3-, CD14- and CD19-positive cells, but only after 18 h of exposure to SPIR. 4 The transcriptional network involving the differentially regulated genes was examined and the results indicate that SPIR affects genes controlled by the transcription factors NF-kappaB, CEBPbeta and MYC. 5 These observations provide new insight into the non-MR-mediated effects of SPIR. PMID:16520746

  2. Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.

    PubMed

    Volat, Fanny E; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

    2012-11-01

    Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

  3. Effects of spironolactone on human blood mononuclear cells: mineralocorticoid receptor independent effects on gene expression and late apoptosis induction

    PubMed Central

    Sønder, Søren Ulrik Salling; Mikkelsen, Marianne; Rieneck, Klaus; Hedegaard, Chris Juul; Bendtzen, Klaus

    2006-01-01

    Spironolactone (SPIR) binds to cytoplasmic mineralocorticoid receptors (MR) and functions as an aldosterone antagonist. Recently, the drug was shown to have an early suppressive effect on several immunoactive and proinflammatory cytokines. To elucidate the mechanism behind this, the four MR-binding steroids SPIR, canrenone, 7α-thiomethyl-spironolactone and aldosterone (ALDO) were investigated for effects on lipopolysaccharide- and phytohemagglutinin-A-activated human blood mononuclear cells. Gene expression was examined after 4 h using microarrays, and SPIR affected 1018 transcripts of the (=) 22,000 probed. In contrast, the SPIR-related steroids affected 17 or fewer transcripts. Combining SPIR and ALDO resulted in 940 affected transcripts, indicating that SPIR has an early gene-regulatory effect independent of MR. The affected genes encode a large number of signalling proteins and receptors, including immunoinflammatory response genes and apoptosis and antiapoptosis genes. Apoptosis was evident in CD3-, CD14- and CD19-positive cells, but only after 18 h of exposure to SPIR. The transcriptional network involving the differentially regulated genes was examined and the results indicate that SPIR affects genes controlled by the transcription factors NF-κB, CEBPβ and MYC. These observations provide new insight into the non-MR-mediated effects of SPIR. PMID:16520746

  4. Idiopathic primary hyperaldosteronism: normalization of plasma aldosterone after one month withdrawal of long-term therapy with aldosterone-receptor antagonist potassium canrenoate.

    PubMed

    Armanini, D; Scaroni, C; Mattarello, M J; Fiore, C; Albiger, N; Sartorato, P

    2005-03-01

    We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate. Therapy had lasted for 3 to 24 yr. Median blood pressure (BP) in the sitting position at the time of diagnosis was 160/100 (ranges 150-200/95-110 mmHg); while 1 month after withdrawal of therapy median BP was 145/90 (ranges 125-160/80-100 mmHg). One month after withdrawal, the ratio aldosterone (ng/dl)/plasma renin activity (ng/ml/h) in the upright position was increased only in 3 cases (median 18, range 6.1-125). We found a significant inverse correlation between the upright aldosterone/plasma renin activity (aldo/PRA) ratio, 1 month after withdrawal, and the number of years of therapy with potassium canrenoate. We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug. These data are consistent with possible regression of idiopathic primary hyperaldosteronism after long-term therapy with potassium canrenoate, or in alternative to a persistent effect of potassium canrenoate, on aldosterone synthesis. PMID:15952408

  5. A novel cell layer without corticosteroid-synthesizing enzymes in rat adrenal cortex: histochemical detection and possible physiological role.

    PubMed

    Mitani, F; Suzuki, H; Hata, J; Ogishima, T; Shimada, H; Ishimura, Y

    1994-07-01

    A stratum of cells that did not contain both aldosterone synthase cytochrome P450 (cytochrome P450aldo) and cytochrome P45011 beta was found immunohistochemically between the zona glomerulosa and the zona fasciculata of the rat adrenal cortex. As cytochromes P450aldo and P45011 beta are the enzymes responsible for the biosynthesis of aldosterone and corticosterone, respectively, the cells there are considered to be incapable of synthesizing both aldosterone and corticosterone. Furthermore, the cells are regarded as inert in producing adrenal androgens, because rat adrenal cortex is known to lack steroid 17 alpha-hydroxylase. Thus, the stratum is composed of cells that do not synthesize any of the major corticosteroids in significant quantities. It was 5-10 cells thick under normal feeding conditions, but diminished to 4-5 cells thick when animals were maintained under Na restriction, which is known to stimulate the secretion of angiotensin-II. When the distribution of 5-bromo-2'-deoxyuridine-labeled nuclei in the adrenocortex from BrdU-administered rats was examined, the stained nuclei were concentrated in and around the cell stratum. The pulse-chase experiments showed that the labeled cells migrated out of this layer and into the zonae fasciculata-reticularis. On the basis of these findings, we suggest that the newly discovered cell layer is the progenitor cell zone of the rat adrenal cortex.

  6. The role of atrial natriuretic peptide (ANP) in cold-induced diuresis (CID)

    SciTech Connect

    Agnew, J.W.; Freund, B.J.; DuBose, D.A.; McKay, J.M.; Hashiro, G.M. Tripler Army Medical Center, Honolulu, HI )

    1991-03-11

    The hormonal control of cold-induced diuresis (CID) remains unresolved. This study investigated the role of ANP, plasma vasopressin (AVP), and aldosterone (ALDO) on CID. Four semi-nude men participated in a 210 min exposure to 15C and 29C air, on separate days. These subjects drank 300 mL of water and had an intravenous saline drip throughout both exposures to replace blood and insensible fluid losses. CID was observed in 15C but not in the 29C experiment, as indicated by a greater urine output. In 15C, atrial natriuretic peptide (ANP) increased after 90 min by 41% and remained elevated for 2 h relative to 29C. No differences were observed in AVP between 15C and 29C. In the 15C versus the 29C experiment, ALDO was approximately 37% lower at the pre, 15 and 90 min time periods. Mean arterial blood pressure was generally greater but only significant at 60 min during the 15C versus the 29C experiment. Urinary NA{sup +} excretion was elevated in 15C relative to 29C while no difference in K{sup +} excretion was observed. Although pressure effects may contribute, the observed natriuresis in the absence of a kaliuresis in the cold suggests a physiological role of ANP in CID.

  7. Photoinduced catalytic synthesis of biologically important metabolites from formaldehyde and ammonia under plausible "prebiotic" conditions

    NASA Astrophysics Data System (ADS)

    Delidovich, I. V.; Taran, O. P.; Simonov, A. N.; Matvienko, L. G.; Parmon, V. N.

    2011-08-01

    The article analyzes new and previously reported data on several catalytic and photochemical processes yielding biologically important molecules. UV-irradiation of formaldehyde aqueous solution yields acetaldehyde, glyoxal, glycolaldehyde and glyceraldehyde, which can serve as precursors of more complex biochemically relevant compounds. Photolysis of aqueous solution of acetaldehyde and ammonium nitrate results in formation of alanine and pyruvic acid. Dehydration of glyceraldehyde catalyzed by zeolite HZSM-5-17 yields pyruvaldehyde. Monosaccharides are formed in the course of the phosphate-catalyzed aldol condensation reactions of glycolaldehyde, glyceraldehyde and formaldehyde. The possibility of the direct synthesis of tetroses, keto- and aldo-pentoses from pure formaldehyde due to the combination of the photochemical production of glycolahyde and phosphate-catalyzed carbohydrate chain growth is demonstrated. Erythrulose and 3-pentulose are the main products of such combined synthesis with selectivity up to 10%. Biologically relevant aldotetroses, aldo- and ketopentoses are more resistant to the photochemical destruction owing to the stabilization in hemiacetal cyclic forms. They are formed as products of isomerization of erythrulose and 3-pentulose. The conjugation of the concerned reactions results in a plausible route to the formation of sugars, amino and organic acids from formaldehyde and ammonia under presumed 'prebiotic' conditions.

  8. Acyclic forms of aldohexoses and ketohexoses in aqueous and DMSO solutions: conformational features studied using molecular dynamics simulations.

    PubMed

    Plazinski, Wojciech; Plazinska, Anita; Drach, Mateusz

    2016-04-14

    The molecular properties of aldohexoses and ketohexoses are usually studied in the context of their cyclic, furanose or pyranose structures which is due to the abundance of related tautomeric forms in aqueous solution. We studied the conformational features of a complete series of D-aldohexoses (D-allose, D-altrose, D-glucose, D-mannose, D-gulose, d-idose, D-galactose and D-talose) and D-ketohexoses (D-psicose, D-fructose, D-sorbose and D-tagatose) as well as of L-psicose by using microsecond-timescale molecular dynamics in explicit water and DMSO with the use of enhanced sampling methods. In each of the studied cases the preferred conformation corresponded to an extended chain structure; the less populated conformers included the quasi-cyclic structures, close to furanose rings and common for both aldo- and ketohexoses. The orientational preferences of the aldehyde or ketone groups are correlated with the relative populations of anomers characteristic of cyclic aldo- and ketohexoses, respectively, thus indicating that basic features of anomeric equilibria are preserved even if hexose molecules are not in their cyclic forms. No analogous relationship is observed in the case of other structural characteristics, such as the preferences of acyclic molecules to form either the furanose-or pyranose-like structures or maintaining the chair-like geometry of pseudo-pyranose rings.

  9. 40Ar/39Ar dating of a Langhian biotite-rich clay layer in the pelagic sequence of the Cònero Riviera, Ancona, Italy

    NASA Astrophysics Data System (ADS)

    Mader, Dieter; Montanari, Alessandro; Gattacceca, Jérôme; Koeberl, Christian; Handler, Robert; Coccioni, Rodolfo

    2001-12-01

    A nearly complete and undisturbed Miocene carbonate sequence is present in the easternmost part of the Umbria-Marche basin, Italy, which is ideal for detailed and integrated stratigraphic investigations of the Miocene Epoch. In this study, we were trying to obtain evidence for the presence or absence of distal ejecta from the 15 Ma Ries impact structure in southern Germany, located about 600 km to the north-northwest of the Umbria-Marche basin. The first step is to find coeval strata in the Umbria-Marche sequence. At the La Vedova section, Cònero Riviera, we dated a volcaniclastic biotite-rich clay layer, the Aldo Level, which is situated within planktonic foraminiferal Zone N8, at 14.9±0.2 Ma, using the 40Ar/39Ar method. Together with detailed geologic and stratigraphic information about the Aldo Level, the resulting age can be used confidentially to calibrate the Langhian stage. Besides providing new constraints on Miocene geochronology, this age can now be used for impact stratigraphic studies. To directly correlate the biotite ages of the La Vedova section with rocks from the Ries impact event, Ries impact glass was also analyzed and found to be coeval. Although unrelated to this impact event, the biotite-rich clay layer should help in the search for evidence of distal ejecta related to the Ries crater.

  10. Relationship between liver and low rumen pH in goat.

    PubMed

    Xie, Z; Jiang, X; Ye, P; Zhang, Y; Ni, Y; Zhuang, S; Shen, X

    2015-01-01

    The aim of this study was to analyze the response of dry goat liver to sub-acute ruminal acidosis induced by a highly concentrated diet. Non-pregnant, non-lactating female Poll-goats (N = 12) were randomly assigned to either a high-concentrate (HG) or a low-concentrate (LG) diet. Low rumen pH was successfully induced with HG (more than 3 h with rumen pH < 5.8). The plasma lipopolysaccharide concentration was significantly decreased in the HG compared with LG group (P < 0.05). Proteomic analysis showed that aldehyde dehydrogenases and microsomal glutathione S-transferase was downregulated in the HG group, whereas aldo-keto reductase was upregulated compared in the LG group. The abundance of mRNA for these proteins were also correspondingly increased (aldehyde dehydrogenases and microsomal glutathione-S-transferase) or decreased (aldo-keto reductase) in the HG group. Malondialdehyde content in the liver was decreased in the HG group compared to the LG group. These data indicate that the expression of hepatic proteins alters the regulation of endogenous lipopolysaccharide during low rumen pH in dry dairy goats. In particular, the protective effect of the liver may occur through inhibition of aldehyde and/or peroxide formation.

  11. Sulfonyl-containing aldophosphamide analogues as novel anticancer prodrugs targeted against cyclophosphamide-resistant tumor cell lines.

    PubMed

    Jain, Monish; Fan, Junying; Baturay, Nesrine Z; Kwon, Chul-Hoon

    2004-07-15

    A series of sulfonyl-group containing analogues of aldophosphamide (Aldo) were synthesized as potential anticancer prodrugs that liberate the cytotoxic phosphoramide mustards (PM, IPM, and tetrakis-PM) via beta-elimination, a nonenzymatic activation mechanism. Kinetic studies demonstrated that all these compounds spontaneously liberate phosphoramide mustards with half-lives in the range of 0.08-15.2 h under model physiological conditions in 0.08 M phosphate buffer at pH 7.4 and 37 degrees C. Analogous to Aldo, the rates of beta-elimination in all compounds was enhanced in reconstituted human plasma under same conditions. The compounds were more potent than the corresponding phosphoramide mustards against V-79 Chinese hamster lung fibroblasts in vitro (IC(50) = 1.8-69.1 microM). Several compounds showed excellent in vivo antitumor activity in CD2F1 mice against both P388/0 (Wild) and P388/CPA (CP-resistant) tumor cell lines.

  12. Metabolism of bupropion by baboon hepatic and placental microsomes

    PubMed Central

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB. PMID:21570381

  13. PREFACE: 11th International Spring Seminar on Nuclear Physics: Shell Model and Nuclear Structure - achievements of the past two decades

    NASA Astrophysics Data System (ADS)

    2015-02-01

    The 11th International Seminar on Nuclear Physics was held in Ischia from May 12 to May 16, 2014. This Seminar was dedicated to Aldo Covello, who has been the promoter of this series of meetings, which started in Sorrento in 1986 and continued with meetings held every two or three years in the Naples area. Aldo's idea was to offer to a group of researchers, actively working in selected fields of Nuclear Physics, the opportunity to confront their points of view in a lively and informal way. The choice for the period of the year, Spring, as well as the sites chosen reflected this intent. The first meeting was of a purely theoretical nature, but it was immediately clear that the scope of these conferences needed to be enlarged calling into play the experimental community. Then, starting from the second meeting, all the following ones have been characterized by fruitful discussion between theoretical and experimental researchers on current achievements and future developments of nuclear structure. This may be read, in fact, as one of the motivating factors for Aldo's election as Fellow of the American Physical Society in 2008 "... for his outstanding contributions to the international nuclear physics community by providing, for over two decades, a venue for theorists and experimentalists to share their latest ideas." The present meeting, organized by Aldo's former students and with the benefit of his suggestions, has maintained this tradition. The title "Shell model and nuclear structure: achievements of the past two decades" recalls that of the 2nd International Spring Seminar "Shell Model and Nuclear Structure: where do we stand?". The main aim of this 11th Seminar was, in fact, to discuss the changes of the past two decades on our view of nuclei in terms of shell structure as well as the perspectives of the shell model, which has been one of the key points in Aldo's research. This point is well accounted by the Opening Speech of Igal Talmi, one of the fathers of the

  14. List of Participants

    NASA Astrophysics Data System (ADS)

    2011-09-01

    AbeTakashiUniversity of Tokyotabe@nt.phys.s.u-tokyo.ac.jp AmusiaMironRacah Institute of Physics, Jerusalemamusia@vms.huji.ac.il BaldoMarcelloINFN Cataniabaldo@ct.infn.it BansalManiePanjab University, Chandigarhbansalmanni@gmail.com BarrancoFranciscoUniversity of Sevillebarranco@us.es BertschGeorgeUniversity of Washington, Seattlebertsch@u.washington.edu BhagwatAmeeyaCBS Mumbaiameeya@kth.se BorderieBernardIPN Orsayborderie@ipno.in2p3.fr CarbonellJaumeLPSC Grenoblejaume.carbonell@lpsc.in2p3.fr CarlsonJoeLos Alamos National Laboratorycarlson@lanl.gov ColòGianlucaINFN - Università degli Studi di Milanocolo@mi.infn.it DanielewiczPawelNSCL, Michigan State Universitydanielewicz@nscl.msu.edu DescouvemontPierreUniversité Libre de Bruxellespdesc@ulb.ac.be Dohet-EralyJérémyUniversité Libre de Bruxellesjdoheter@ulb.ac.be DraayerJerryLouisiana State Universitydraayer@lsu.edu DufourMarianneIPHC, Université de Strasbourgmarianne.dufour@ires.in2p3.fr DuguetThomasCEA Saclaythomas.duguet@cea.fr DukelskyJorgeCSIC Madriddukelsky@iem.cfmac.csic.es EbranJean-PaulCEA-DAM, Arpajonebran@ipno.in2p3.fr FreerMartinUniversity of Birminghamm.freer@bham.ac.uk FujiiShinichiroUniversity of Tokyosfujii@cns.s.u-tokyo.ac.jp FunakiYasuroRIKEN Nishina Center, Wakofunaki@riken.jp GrassoMarcellaIPN Orsaygrasso@ipno.in2p3.fr HaginoKouichiTohoku Universityhagino@nucl.phys.tohoku.ac.jp HansenHubertUniversité Claude Bernard Lyon 1hansen@ipnl.in2p3.fr HolzmannMarkusLPMMC Grenoblemarkus@lptl.jussieu.fr HoriuchiHisashiRCNP, Osaka Universityhoriuchi@rcnp.osaka-u.ac.jp HoriuchiWataruGSI Darmstadtw.horiuchi@gsi.de HupinGuillaumeGANIL, Caenhupin@ganil.fr JinMengHuazhong Normal University, Wuhanjinm@iopp.ccnu.edu.cn KamimuraMasayasuRIKEN Nishina Center, Wakomkamimura@riken.jp Kanada-En'yoYoshikoKyoto Universityyenyo@ruby.scphys.kyoto-u.ac.jp KatoKiyoshiHokkaido University, Sapporokato@nucl.sci.hokudai.ac.jp KawabataTakahiroKyoto Universitykawabata@scphys.kyoto-u.ac.jp KhanEliasIPN Orsaykhan@ipno.in2p3.fr

  15. Testing SLURM open source batch system for a Tierl/Tier2 HEP computing facility

    NASA Astrophysics Data System (ADS)

    Donvito, Giacinto; Salomoni, Davide; Italiano, Alessandro

    2014-06-01

    In this work the testing activities that were carried on to verify if the SLURM batch system could be used as the production batch system of a typical Tier1/Tier2 HEP computing center are shown. SLURM (Simple Linux Utility for Resource Management) is an Open Source batch system developed mainly by the Lawrence Livermore National Laboratory, SchedMD, Linux NetworX, Hewlett-Packard, and Groupe Bull. Testing was focused both on verifying the functionalities of the batch system and the performance that SLURM is able to offer. We first describe our initial set of requirements. Functionally, we started configuring SLURM so that it replicates all the scheduling policies already used in production in the computing centers involved in the test, i.e. INFN-Bari and the INFN-Tier1 at CNAF, Bologna. Currently, the INFN-Tier1 is using IBM LSF (Load Sharing Facility), while INFN-Bari, an LHC Tier2 for both CMS and Alice, is using Torque as resource manager and MAUI as scheduler. We show how we configured SLURM in order to enable several scheduling functionalities such as Hierarchical FairShare, Quality of Service, user-based and group-based priority, limits on the number of jobs per user/group/queue, job age scheduling, job size scheduling, and scheduling of consumable resources. We then show how different job typologies, like serial, MPI, multi-thread, whole-node and interactive jobs can be managed. Tests on the use of ACLs on queues or in general other resources are then described. A peculiar SLURM feature we also verified is triggers on event, useful to configure specific actions on each possible event in the batch system. We also tested highly available configurations for the master node. This feature is of paramount importance since a mandatory requirement in our scenarios is to have a working farm cluster even in case of hardware failure of the server(s) hosting the batch system. Among our requirements there is also the possibility to deal with pre-execution and post

  16. Thermo-optical vacuum testing of Galileo In-Orbit Validation laser retroreflectors

    NASA Astrophysics Data System (ADS)

    Dell'Agnello, S.; Boni, A.; Cantone, C.; Ciocci, E.; Contessa, S.; Delle Monache, G.; Lops, C.; Martini, M.; Patrizi, G.; Porcelli, L.; Salvatori, L.; Tibuzzi, M.; Intaglietta, N.; Tuscano, P.; Mondaini, C.; Maiello, M.; Doyle, D.; García-Prieto, R.; Navarro-Reyes, D.

    2016-06-01

    The Galileo constellation is a space research and development program of the European Union to help navigate users all over the world. The Galileo IOV (In-Orbit Validation) are the first test satellites of the Galileo constellation and carry satellite laser retroreflectors as part of their payload systems for precision orbit determination and performance assessment. INFN-LNF SCF_Lab (Satellite/lunar/GNSS laser ranging/altimetry and Cube/microsat Characterization Facilities Laboratory) has been performing tests on a sample of the laser array segment under the Thermo-optical vacuum testing of Galileo IOV laser retro-reflectors of Galileo IOV LRA project, as defined in ESA-INFN Contract No. 4000108617/13/NL/PA. We will present the results of FFDP (Far Field Diffraction Pattern) and thermal relaxation times measurements in relevant space conditions of Galileo IOV CCRs (Cube Corner Retroreflectors) provided by ESA-ESTEC. A reference for the performance of laser ranging on Galileo satellites is the FFDP of a retroreflector in its design specifications and a Galileo retroreflector, in air and isothermal conditions, should have a minimum return intensity within the range [ 0.55 ×106m2- 2.14 ×106m2 ] (ESA-INFN, 2013). Measurements, performed in SCF_Lab facility, demonstrated that the 7 Galileo IOV laser retroreflectors under test were compliant with design performance expectations (Porcelli et al., 2015). The kind of tests carried out for this activity are the first performed on spare Galileo IOV hardware, made available after the launch of the four Galileo IOV satellites (2011 and 2012), which were the operational core of the constellation. The characterisation of the retroreflectors against their design requirements is important because LRAs (Laser Retroreflector Arrays) will be flown on all Galileo satellites.

  17. Implementation and use of a highly available and innovative IaaS solution: the Cloud Area Padovana

    NASA Astrophysics Data System (ADS)

    Aiftimiei, C.; Andreetto, P.; Bertocco, S.; Biasotto, M.; Dal Pra, S.; Costa, F.; Crescente, A.; Dorigo, A.; Fantinel, S.; Fanzago, F.; Frizziero, E.; Gulmini, M.; Michelotto, M.; Sgaravatto, M.; Traldi, S.; Venaruzzo, M.; Verlato, M.; Zangrando, L.

    2015-12-01

    While in the business world the cloud paradigm is typically implemented purchasing resources and services from third party providers (e.g. Amazon), in the scientific environment there's usually the need of on-premises IaaS infrastructures which allow efficient usage of the hardware distributed among (and owned by) different scientific administrative domains. In addition, the requirement of open source adoption has led to the choice of products like OpenStack by many organizations. We describe a use case of the Italian National Institute for Nuclear Physics (INFN) which resulted in the implementation of a unique cloud service, called ’Cloud Area Padovana’, which encompasses resources spread over two different sites: the INFN Legnaro National Laboratories and the INFN Padova division. We describe how this IaaS has been implemented, which technologies have been adopted and how services have been configured in high-availability (HA) mode. We also discuss how identity and authorization management were implemented, adopting a widely accepted standard architecture based on SAML2 and OpenID: by leveraging the versatility of those standards the integration with authentication federations like IDEM was implemented. We also discuss some other innovative developments, such as a pluggable scheduler, implemented as an extension of the native OpenStack scheduler, which allows the allocation of resources according to a fair-share based model and which provides a persistent queuing mechanism for handling user requests that can not be immediately served. Tools, technologies, procedures used to install, configure, monitor, operate this cloud service are also discussed. Finally we present some examples that show how this IaaS infrastructure is being used.

  18. PREFACE: International Seminar on Strong and Electromagnetic Interactions in High Energy Collisions 2012

    NASA Astrophysics Data System (ADS)

    Giardina, Giorgio; Sandorfi, Andrew; Pedroni, Paolo

    2013-03-01

    The International Seminar 'Strong and Electromagnetic Interaction in High Energy Collisions' was held in the Conference Hall 'Ettore Majorana' of the Department of Physics in Messina, Italy on October 12, 2012. The Seminar was organized by the University of Messina and 'Fondazione Bonino-Pulejo', with the aim of presenting and discussing the results of the current experiments and also new plans involving research at INFN-LNF (Italy), JLAB (USA), LHC-CERN, ELSA (Bonn), MAMI (Mainz). The main purpose of this Seminar was to deal with aspects of electromagnetic and strong forces by meson photoproduction and the electron-positron collider, and to search for dark energy. The recent results on hadron contributions to the muon anomalous magnetic moment and kaon interferometry at the DAFNE facility were also discussed. Editors: Giorgio Giardina (University of Messina), Andrew M Sandorfi (Thomas Jefferson National Accelerator Facility, Newport News, USA), Paolo Pedroni (INFN 'Sezione di Pavia') Organizing Committee: Chairman: G Giardina (Messina - Italy) Co-Chairman: A M Sandorfi (Newport News, USA) Co-Chairman: P Pedroni (Pavia - Italy) Scientific Secretary: G Mandaglio (University of Messina - Italy) Organizing Institutions: University of Messina Fondazione Bonino-Pulejo (Messina) Topics: Meson photoproduction and baryon resonances Muon anomaly (g-2) Recent results in experiments at the Large Hadron Collider Kaon interferometry Local Organizing Committee: F Curciarello, V De Leo, G Fazio, G Giardina, G Mandaglio, M Romaniuk Sponsored by: University of Messina, Fondazione Bonino-Pulejo (Messina), INFN Sezione di Catania Web-Site: http://newcleo.unime.it/IntSem2012

  19. An intrinsically safe facility for forefront research and training on nuclear technologies — An example of accelerator: the SPES cyclotron

    NASA Astrophysics Data System (ADS)

    Maggiore, M.; Lombardi, A.; Piazza, L. A. C.; Prete, G.

    2014-04-01

    The SPES project, under construction at INFN, Laboratori Nazionali di Legnaro, is a research facility for nuclear and applied physics, based on a high-current H- cyclotron with two exits. One exit will be devoted to supply an ISOL facility for the production of radioactive beams, the second one can be used as driver for the ADS system. The main characteristics of the cyclotron are described together with the main building designed to operate high-current proton beams according to radioprotection rules.

  20. Constraint algebra for interacting quantum systems

    NASA Astrophysics Data System (ADS)

    Fubini, S.; Roncadelli, M.

    1988-04-01

    We consider relativistic constrained systems interacting with external fields. We provide physical arguments to support the idea that the quantum constraint algebra should be the same as in the free quantum case. For systems with ordering ambiguities this principle is essential to obtain a unique quantization. This is shown explicitly in the case of a relativistic spinning particle, where our assumption about the constraint algebra plus invariance under general coordinate transformations leads to a unique S-matrix. On leave from Dipartimento di Fisica Nucleare e Teorica, Università di Pavia and INFN, I-27100 Pavia, Italy.

  1. Injection of auxiliary electrons for increasing the plasma density in highly charged and high intensity ion sources

    NASA Astrophysics Data System (ADS)

    Odorici, F.; Malferrari, L.; Montanari, A.; Rizzoli, R.; Mascali, D.; Castro, G.; Celona, L.; Gammino, S.; Neri, L.

    2016-02-01

    Different electron guns based on cold- or hot-cathode technologies have been developed since 2009 at INFN for operating within ECR plasma chambers as sources of auxiliary electrons, with the aim of boosting the source performances by means of a higher plasma lifetime and density. Their application to microwave discharge ion sources, where plasma is not confined, has required an improvement of the gun design, in order to "screen" the cathode from the plasma particles. Experimental tests carried out on a plasma reactor show a boost of the plasma density, ranging from 10% to 90% when the electron guns are used, as explained by plasma diffusion models.

  2. The X-ray machine for the examination of quantum mechanics

    NASA Astrophysics Data System (ADS)

    Curceanu, Catalina; Bartalucci, Sergio; Bassi, Angelo; Bazzi, Massimiliano; Bertolucci, Sergio; Berucci, Carolina; Bragadireanu, Alexandru Mario; Cargnelli, Michael; Clozza, Alberto; de Paolis, Luca; Di Matteo, Sergio; Donadi, Sandro; D’Uffizi, Alessandro; Egger, Jean-Pierre; Guaraldo, Carlo; Iliescu, Mihail; Laubenstein, Matthias; Marton, Johann; Milotti, Edoardo; Pichler, Andreas; Pietreanu, Dorel; Piscicchia, Kristian; Ponta, Titus; Scordo, Alessandro; Shi, Hexi; Sirghi, Diana; Sirghi, Florin; Sperandio, Laura; Doce, Oton Vazquez; Zmeskal, Johann

    2016-05-01

    By performing X-rays measurements in the underground laboratory of Gran Sasso, LNGS-INFN, we test a basic principle of quantum mechanics: the Pauli exclusion principle (PEP). In the future, we aim to use a similar experimental technique to search for X-rays as a signature of the spontaneous collapse of the wave function predicted by continuous spontaneous localization theories. We present the achieved results of the VIP experiment and the future plans to gain two orders of magnitude in testing PEP with the recently VIP2 setup installed at Gran Sasso.

  3. Injection of auxiliary electrons for increasing the plasma density in highly charged and high intensity ion sources.

    PubMed

    Odorici, F; Malferrari, L; Montanari, A; Rizzoli, R; Mascali, D; Castro, G; Celona, L; Gammino, S; Neri, L

    2016-02-01

    Different electron guns based on cold- or hot-cathode technologies have been developed since 2009 at INFN for operating within ECR plasma chambers as sources of auxiliary electrons, with the aim of boosting the source performances by means of a higher plasma lifetime and density. Their application to microwave discharge ion sources, where plasma is not confined, has required an improvement of the gun design, in order to "screen" the cathode from the plasma particles. Experimental tests carried out on a plasma reactor show a boost of the plasma density, ranging from 10% to 90% when the electron guns are used, as explained by plasma diffusion models.

  4. Design of a 10-bit segmented current-steering digital-to-analog converter in CMOS 65 nm technology for the bias of new generation readout chips in high radiation environment

    NASA Astrophysics Data System (ADS)

    De Robertis, G.; Loddo, F.; Mattiazzo, S.; Pacher, L.; Pantano, D.; Tamma, C.

    2016-01-01

    A new pixel front end chip for HL-LHC experiments in CMOS 65nm technology is under development by the CERN RD53 collaboration together with the Chipix65 INFN project. This work describes the design of a 10-bit segmented current-steering Digital-to-Analog Converter (DAC) to provide a programmable bias current to the analog blocks of the circuit. The main requirements are monotonicity, good linearity, limited area consumption and radiation hardness up to 10 MGy. The DAC was prototyped and electrically tested, while irradiation tests will be performed in Autumn 2015.

  5. RF and Magnetic Measurements on the SPARC Photoinjector and Solenoid at UCLA

    SciTech Connect

    Rosenzweig, J.B.; Cook, A.M.; Dunning, M.P.; Frigola, P.; Travish, G.; Sanelli, C.; Tazzioli, F.; Palmer, D.T.; /SLAC

    2006-01-30

    The rf photocathode gun and the solenoid for the SPARC project at INFN-LNF (Frascati) have been fabricated and undergone initial testing at UCLA. The advanced aspects of the design of these devices are detailed. Final diagnosis of the tuning of the RF gun performance, including operating mode frequency and field balance, is described. The emittance compensating solenoid magnet, which is designed to be tuned in longitudinal position by differential excitation of the coils, has been measured using Hall probe scans for field profiling, and pulsed wire methods to determine the field center. Comparisons between measurements and the predictions of design codes are made.

  6. RIB in-flight production and the facility EXOTIC at LNL

    SciTech Connect

    Mazzocco, Marco

    2014-05-09

    The production of Radioactive Ion Beams (RIBs) via the In-Flight technique is reviewed. This separation method typically employs four main production mechanisms: (i) Projectile Fragmentation; (ii) Projectile Fission; (iii) Nuclear Fusion and (iv) Direct Processes in Inverse Kinematics. We will concentrate particularly on the last mechanism, the one used by the facility EXOTIC at the INFN-Laboratori Nazionali di Legnaro (LNL) for the production of light RIBs. An extensive description of the facility and a brief overview of the most recent scientific achievements with {sup 7}Be and {sup 17}F are given.

  7. Uranium Groundwater Monitoring and Seismic Analysis: A Case Study of the Gran Sasso Hydrogeological Basin, Italy

    NASA Astrophysics Data System (ADS)

    Ciarletti, Marta; Plastino, Wolfango; Peresan, Antonella; Nisi, Stefano; Copia, Lorenzo; Panza, Giuliano F.; Povinec, Pavel P.

    2016-04-01

    Uranium groundwater anomalies, observed before the L'Aquila earthquake (April 6th, 2009) and before the seismic swarm, which occurred in the second half of 2010, represent a key geochemical signal of a progressive increase of deep fluids fluxes at middle-lower crustal levels associated with the geodynamics of the earthquake. In this paper, temporal variations of uranium groundwater are studied in association with the seismic pattern around Gran Sasso National Laboratory (LNGS-INFN). The normalized seismic energy release and the number of earthquakes are analyzed in detail by means of monthly sliding time windows. They are compared with uranium anomalies to highlight any possible correlation.

  8. The Ring Counter (RCo): A high resolution IC Si CsI(Tl) device for heavy ion reaction studies at 10 30 MeV/A

    NASA Astrophysics Data System (ADS)

    Moroni, A.; Bruno, M.; Bardelli, L.; Barlini, S.; Brambilla, S.; Casini, G.; Cavaletti, R.; Chiari, M.; Cortesi, A.; D'Agostino, M.; De Sanctis, J.; Geraci, E.; Giordano, G.; Giussani, A.; Gramegna, F.; Guiot, B.; Kravchuk, V.; Lanchais, A.; Margagliotti, G. V.; Nannini, A.; Ordine, A.; Piantelli, S.; Vannini, G.; Vannucci, L.

    2006-01-01

    An annular detector (Ring Counter, RCo) is presented, which has been designed and built to detect and identify in mass and charge light charged particles and fragments with very low energy thresholds and high energy resolution. It complements the GARFIELD apparatus, operating at INFN Laboratori Nazionali di Legnaro, to detect the forward emitted products of nuclear heavy ion reactions. It consists of eight sectors of a three-stage telescope, each one formed by an ionization chamber followed by eight strips of a silicon detector and by two CsI(Tl) scintillators. Construction features and performances are described and discussed in details.

  9. Test beam results with a sampling calorimeter of cerium fluoride scintillating crystals and tungsten absorber plates for calorimetry at the HL-LHC

    NASA Astrophysics Data System (ADS)

    Becker, R.; Dissertori, G.; Djambazov, L.; Donegà, M.; Dröge, M.; Haller, C.; Horisberger, U.; Lustermann, W.; Nessi-Tedaldi, F.; Quittnat, M.; Pandolfi, F.; Peruzzi, M.; Schönenberger, M.; Cavallari, F.; Dafinei, I.; Diemoz, M.; D`Imperio, G.; del Re, D.; Gelli, S.; Jorda Lope, C.; Meridiani, P.; Micheli, F.; Nuccetelli, M.; Organtini, G.; Paramatti, R.; Pellegrino, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Soffi, L.; Tabarelli de Fatis, T.; Martelli, A.; Monti, V.; Pastrone, N.; Trapani, P. P.; Candelise, V.; Della Ricca, G.

    2016-07-01

    A sampling calorimeter using cerium fluoride scintillating crystals as active material, interleaved with absorber plates made of tungsten, and read out by wavelength-shifting fibres has been tested with high-energy electron beams at the CERN SPS H4 beam line, as well as with lower-energy beams at the INFN Frascati Beam Test Facility in Italy. Energy resolution studies revealed a low stochastic term (< 10 % /√{ E }). This result, combined with high radiation hardness of the material used, marks this sampling calorimeter as a good candidate for the detectors' forward regions during the high luminosity phase of LHC.

  10. Commissioning of polarized-proton and antiproton beams at Fermilab

    SciTech Connect

    Yokosawa, A.

    1988-05-04

    The author described the polarized-proton and polarized-antiproton beams up to 200 GeV/c at Fermilab. The beam line, called MP, consists of the 400-m long primary and 350-m long secondary beam line followed by 60-m long experimental hall. We discuss the characteristics of the polarized beams. The Fermilab polarization projects are designated at E-581/704 initiated and carried out by an international collaboration, Argonne (US), Fermilab (US), Kyoto-Kyushu-Hiroshima-KEK (Japan), LAPP (France), Northwestern University (US), Los Alamos Laboratory (US), Rice (US), Saclay (France), Serpukhov (USSR), INFN Trieste (Italy), and University of Texas (US).

  11. Campaign of measurements to probe the good performance of the new array FARCOS for spectroscopy and correlations.

    NASA Astrophysics Data System (ADS)

    Acosta, L.; Andolina, R.; Auditore, L.; Boiano, C.; Cardella, G.; Castoldi, A.; D'Andrea, M.; De Filippo, E.; De Luca, S.; Dell'Aquila, D.; Francalanza, L.; Gnoffo, B.; Guazzoni, C.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Parsani, T.; Pirrone, S.; Politi, G.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Russotto, P.; Saccá, G.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.; Zambon, P.

    2016-07-01

    During the last four years, several measurements have been carried out where the capabilities of FARCOS array were tested. In some of this occasions, FARCOS was coupled to the 4π array CHIMERA, permanently placed at INFN-Laboratori Nazionali del Sud, Catania in order to be tested in real experimental measurements. At the present situation, the FARCOS demonstrator is formed by 4 telescopes out of the originally 20 that will constitute the final array. Here are presented some preliminary results obtained with the new array, probing its qualities and showing the effectiveness of FARCOS telescopes. The initial encouraging results support the construction of the complete array.

  12. Laser-capillary interaction for the EXIN project

    NASA Astrophysics Data System (ADS)

    Bisesto, F. G.; Anania, M. P.; Bacci, A. L.; Bellaveglia, M.; Chiadroni, E.; Cianchi, A.; Curcio, A.; Di Giovenale, D.; Di Pirro, G.; Ferrario, M.; Galletti, M.; Gallo, A.; Ghigo, A.; Marocchino, A.; Mostacci, A.; Petrarca, M.; Pompili, R.; Rossi, A. R.; Serafini, L.; Vaccarezza, C.

    2016-09-01

    The EXIN project is under development within the SPARC_LAB facility of the National Laboratory of Frascati (LNF-INFN). This project aims to accelerate pre-existing electron bunches with high brightness by exploiting the wakefield plasma acceleration technique, while preserving the initial brightness. The wakefield is excited inside a dielectric capillary by high intensity laser pulses produced by the FLAME laser interacting with a gas. In this work, we present numerical simulations in order to optimize energy coupling between our laser with super-Gaussian transverse profile and a dielectric capillary. Moreover, an overview of the experimental layout will be given.

  13. The FLUKA Code: An Overview

    NASA Technical Reports Server (NTRS)

    Ballarini, F.; Battistoni, G.; Campanella, M.; Carboni, M.; Cerutti, F.; Empl, A.; Fasso, A.; Ferrari, A.; Gadioli, E.; Garzelli, M. V.; Lantz, M.; Liotta, M.; Mairani, A.; Mostacci, A.; Muraro, S.; Ottolenghi, A.; Pelliccioni, M.; Pinsky, L.; Ranft, J.; Roesler, S.; Sala, P. R.; Scannicchio, D.; Trovati, S.; Villari, R.; Wilson, T.

    2006-01-01

    FLUKA is a multipurpose Monte Carlo code which can transport a variety of particles over a wide energy range in complex geometries. The code is a joint project of INFN and CERN: part of its development is also supported by the University of Houston and NASA. FLUKA is successfully applied in several fields, including but not only, particle physics, cosmic ray physics, dosimetry, radioprotection, hadron therapy, space radiation, accelerator design and neutronics. The code is the standard tool used at CERN for dosimetry, radioprotection and beam-machine interaction studies. Here we give a glimpse into the code physics models with a particular emphasis to the hadronic and nuclear sector.

  14. A case study for the handling of data in a skimming control system

    NASA Astrophysics Data System (ADS)

    Stevanato, Elisa; Stroili, Roberto

    2009-07-01

    This work focuses on the architectural, methodological and technological aspect of handling huge amounts of data. In this summary we particularly focus our attention on the description of a special system built to support large scale data access. The work comes from the need to develop a special purpose skimming control system; this system has been designed as a collaboration between the Stanford Linear Accelerator Center (SLAC, USA), and the Istituto Nazionale di Fisica Nucleare (INFN, National Istitute of Nuclear Physic, Padua, Italy). The goal was to provide the handle of more than 10 7 files, representing Physics data collected by the BaBar experiment.

  15. Diagnostic for the radiotherapy use of laser-accelerated proton beams

    NASA Astrophysics Data System (ADS)

    Cirrone, G. A. P.; Cuttone, G.; Maggiore, M.; Torrisi, L.; Tudisco, F.

    2010-10-01

    A research project, LILIA (Laser Induced Light Ion Acceleration), has been funded at INFN (Italian Institute for Nuclear Physics) with the aim of studying the mechanisms of charged particle acceleration by high power lasers. In Italy, at LNF-INFN of Frascati, a high power laser (intensity in the range 1020-1021 W/cm2, 10 Hz repetition rate and high contrast, of the order of 1010, between main pulse and pre-pulse) named FLAME will be operative within 2010. The activities related to this project, along with the FLAME peculiarities, will result in a significant synergy to improve research on plasma acceleration in Italy. In this frame our group is involved in the design and construction of a spectrometer, based on the Thomson configuration, in order to diagnose the ion ejection from the laser-generated plasma. This kind of analyzer allows retrieval of most of the information regarding the energy and species of beams produced from a single laser shot.The main goal is to realize a compact system which is both very practical and optimized with regards to the mass and energy resolution of particles obtained by laser-plasma interactions. The preliminary design has to be able to analyze and resolve beams of protons and ions up to a total energy of 10 MeV. However, the technical choices adopted in this prototype have to be applied in the final device, which concerns a challenging spectrograph able to analyze beams of 150 MeV of total energy. An intensive study by means of 3D electromagnetic FEM code and beam dynamics was accomplished, and the results will be shown. The first prototype of the spectrometer is being realized and tested at LNS-INFN of Catania (Italy). After magnetic and electric measurements, the device will be calibrated, and the detectors will be tested with proton and carbon beams delivered by the accelerators operating at LNS-INFN of Catania within the expected energy range (0.1-10 MeV) and for different charge-to-mass ratios (Q=+1 to+6). The results of

  16. DANTE: control system for DAΦNE based on Macintosh and LabVIEW

    NASA Astrophysics Data System (ADS)

    Di Pirro, G.; Milardi, C.; Stecchi, A.; Trasatti, L.

    1994-12-01

    DANTE (DAΦNE new tools environment) is the control system for the DAΦNE Φ-factory under construction at the Frascati National Laboratories of the Italian Institute for Nuclear Physics (INFN). The main design goal has been to keep the software simple and easy to debug. Commercial components have been used whenever possible, with a preference for widely diffused and well established products, as opposed to"standards". Macintosh computers are used throughout the system and LabVIEW has been chosen as development environment. We strongly oppose the "start from scratch" philosophy.

  17. Isospin Effects in Heavy-Ion Collisions: Some Results From CHIMERA Experiments At LNS And Perspectives With Radioactive Beams

    SciTech Connect

    Cardella, G.; De Filippo, E.; Pagano, A.; Papa, M.; Pirrone, S.; Verde, G.; Amorini, F.; Cavallaro, S.; Lombardo, I.; Porto, F.; Rizzo, F.; Russotto, P.; Anzalone, A.; Maiolino, C.; Arena, N.; Geraci, E.; Grassi, L.; Lo Nigro, S.; Politi, G.; Auditore, L.

    2009-05-04

    CHIMERA is a 4{pi} multidetector for charged particles available at Laboratori Nazionali del Sud (INFN-LNS). A new method to measure the time scale of the emission of nuclear fragments is described, together with some applications in the field of the isospin dynamics of heavy-ion collisions. Competition between fusion-like and binary reactions near the energy threshold for nuclear multifragmentation is discussed. Opportunities are pointed out to use the detector at low and intermediate energies using the kinematical-coincidence method.

  18. Response function of the magnetic spectrometer PRISMA for the multinucleon transfer reaction {sup 40}Ar+{sup 208}Pb

    SciTech Connect

    Mijatovic, T.; Szilner, S.; Corradi, L.; Courtin, S.; Farnea, E.; Fioretto, E.; Gadea, A.; Goasduff, A.; Haas, F.; Jelavic-Malenica, D.; Lunardi, S.; Mengoni, D.; Montagnoli, G.; Montanari, D.; Pollarolo, G.; Recchia, F.; Sahin, E.; Scarlassara, F.; Soic, N.; Stefanini, A. M.; and others

    2012-10-20

    Multinucleon transfer reaction {sup 40}Ar+{sup 208}Pb has been investigated with the PRISMA-CLARA experimental setup in LNL, INFN, Italy. The experimental differential cross sections have been obtained for different transfer channels by measuring more than {Delta}{theta}{sub lab} = 20 Degree-Sign covered by three angular settings of PRISMA. Results have been compared with the semiclassical calculation GRAZING. Since the understanding of the reaction mechanism depends strongly on the determination of absolute cross section, effect of transport of ions through PRISMA has been studied via a Monte Carlo simulation code.

  19. The Archimedes experiment

    NASA Astrophysics Data System (ADS)

    Calloni, E.; Caprara, S.; Laurentis, M. De; Esposito, G.; Grilli, M.; Majorana, E.; Pepe, G. P.; Petrarca, S.; Puppo, P.; Rapagnani, P.; Ricci, F.; Rosa, L.; Rovelli, C.; Ruggi, P.; Saini, N. L.; Stornaiolo, C.; Tafuri, F.

    2016-07-01

    Archimedes is an INFN-funded pathfinder experiment aimed at verifying the feasibility of measuring the interaction of vacuum fluctuations with gravity. The final experiment will measure the force exerted by the gravitational field on a Casimir cavity whose vacuum energy is modulated with a superconductive transition, by using a balance as a small force detector. Archimedes is two-year project devoted to test the most critical experimental aspects, in particular the balance resonance frequency and quality factor, the thermal modulation efficiency and the superconductive sample realization.

  20. Status report of ICARUS T600

    NASA Astrophysics Data System (ADS)

    Fava, A.

    2012-08-01

    ICARUS T600 at the INFN-LNGS Gran Sasso Laboratory is the first underground large mass Liquid Argon TPC: exposed to the CERN-CNGS neutrino beam, it has smoothly began taking data since October 2010. Its excellent resolution and 3D imaging allow an unprecedented event visualization quality combined with a good calorimetric reconstruction and the electronic event processing. In addition to the νμ → ντ oscillation and sterile neutrino search, atmospheric neutrino and matter stability will be studied.

  1. Mono-energetic ions emission by nanosecond laser solid target irradiation

    NASA Astrophysics Data System (ADS)

    Muoio, A.; Tudisco, S.; Altana, C.; Lanzalone, G.; Mascali, D.; Cirrone, G. A. P.; Schillaci, F.; Trifirò, A.

    2016-09-01

    An experimental campaign aiming to investigate the acceleration mechanisms through laser-matter interaction in nanosecond domain has been carried out at the LENS (Laser Energy for Nuclear Science) laboratory of INFN-LNS, Catania. Pure Al targets were irradiated by 6 ns laser pulses at different pumping energies, up to 2 J. Advanced diagnostics tools were used to characterize the plasma plume and ion production. We show the preliminary results of this experimental campaign, and especially the ones showing the production of multicharged ions having very narrow energy spreads.

  2. NUMEN Project @ LNS : Heavy ions double charge exchange reactions towards the 0νββ nuclear matrix element determination

    SciTech Connect

    Agodi, C. Calabretta, L.; Calanna, A.; Carbone, D.; Cavallaro, M.; Colonna, M.; Cuttone, G.; Finocchiaro, P.; Pandola, L.; Rifuggiato, D.; Tudisco, S.; Cappuzzello, F.; Greco, V.; Bonanno, D. L.; Bongiovanni, D. G.; Longhitano, F.; Branchina, V.; Foti, A.; Lo Presti, D.; Lanzalone, G.; and others

    2015-10-28

    In the NUMEN Project it is proposed an innovative technique to access the nuclear matrix elements entering in the expression of the life-time of the neutrinoless double beta decay, using relevant cross sections of double charge exchange reactions. A key aspect is the use of MAGNEX large acceptance magnetic spectrometer, for the detection of the ejectiles, and of the INFN Laboratori Nazionali del Sud (LNS) K800 Superconducting Cyclotron (CS), for the acceleration of the required high resolution and low emittance heavy-ion beams.

  3. A 16 channel frequency-domain-modulation readout system with custom superconducting LC filters for the SWIPE instrument of the balloon-borne LSPE experiment

    NASA Astrophysics Data System (ADS)

    Signorelli, G.; Baldini, A. M.; Bemporad, C.; Biasotti, M.; Cei, F.; Ceriale, V.; Corsini, D.; Fontanelli, F.; Galli, L.; Gallucci, G.; Gatti, F.; Incagli, M.; Grassi, M.; Nicolò, D.; Spinella, F.; Vaccaro, D.; Venturini, M.

    2016-07-01

    We present the design, implementation and first tests of the superconducting LC filters for the frequency domain readout of spiderweb TES bolometers of the SWIPE experiment on the balloon-borne LSPE mission which aims at measuring the linear polarization of the Cosmic Microwave Background at large angular scales to find the imprint of inflation on the B-mode CMB polarization. LC filters are designed, produced and tested at the INFN sections of Pisa and Genoa where thin film deposition and cryogenic test facilities are present, and where also the TES spiderweb bolometers are being produced.

  4. Particle Dark Matter and DAMA/LIBRA

    SciTech Connect

    Bernabei, R.; Nozzoli, F.; Belli, P.; Cappella, F.; D'Angelo, A.; Prosperi, D.; Cerulli, R.; Dai, C. J.; He, H. L.; Ma, X. H.; Sheng, X. D.; Wang, R. G.; Montecchia, F.; Ye, Z. P.

    2010-03-26

    The DAMA/LIBRA set-up (about 250 kg highly radiopure NaI(Tl) sensitive mass) is running at the Gran Sasso National Laboratory of the I.N.F.N.. The first DAMA/LIBRA results confirm the evidence for the presence of a Dark Matter particle component in the galactic halo, as pointed out by the former DAMA/NaI set-up; cumulatively the data support such evidence at 8.2 sigma C.L. and satisfy all the many peculiarities of the Dark Matter annual modulation signature. The main aspects and prospects of this model independent experimental approach will be outlined.

  5. SuperB: An opportunity to study baryons with beauty and bottom super-nuclei

    NASA Astrophysics Data System (ADS)

    Feliciello, A.

    2012-05-01

    SuperB is an INFN flagship project for a new high-luminosity heavy-flavor factory. Along with its companion detector, it is dedicated to the search for CP violation effects in the B meson sector with the aim of looking for direct and indirect signals of new physics, beyond the Standard Model. However it could offer as well the opportunity for a systematic, high-statistics study of b baryon properties and for a search for bottom super-nuclei, that is bound nuclear systems with an explicit content of beauty.

  6. Detectors based on silicon photomultiplier arrays for medical imaging applications

    SciTech Connect

    Llosa, G.; Barrio, J.; Cabello, J.; Lacasta, C.; Oliver, J. F.; Stankova, V.; Solaz, C.

    2011-07-01

    Silicon photomultipliers (SiPMs) have experienced a fast development and are now employed in different research fields. The availability of 2D arrays that provide information of the interaction position in the detector has had a high interest for medical imaging. Continuous crystals combined with segmented photodetectors can provide higher efficiency than pixellated crystals and very high spatial resolution. The IRIS group at IFIC is working on the development of detector heads based on continuous crystals coupled to SiPM arrays for different applications, including a small animal PET scanner in collaboration with the Univ. of Pisa and INFN Pisa, and a Compton telescope for dose monitoring in hadron therapy. (authors)

  7. The FLUKA Code: an Overview

    SciTech Connect

    Ballarini, F.; Battistoni, G.; Campanella, M.; Carboni, M.; Cerutti, F.; Empl, A.; Fasso, A.; Ferrari, A.; Gadioli, E.; Garzelli, M.V.; Lantz, M.; Liotta, M.; Mairani, A.; Mostacci, A.; Muraro, S.; Ottolenghi, A.; Pelliccioni, M.; Pinsky, L.; Ranft, J.; Roesler, S.; Sala, P.R.; /Milan U. /INFN, Milan /Pavia U. /INFN, Pavia /CERN /Siegen U. /Houston U. /SLAC /Frascati /NASA, Houston /ENEA, Frascati

    2005-11-09

    FLUKA is a multipurpose Monte Carlo code which can transport a variety of particles over a wide energy range in complex geometries. The code is a joint project of INFN and CERN: part of its development is also supported by the University of Houston and NASA. FLUKA is successfully applied in several fields, including but not only, particle physics, cosmic ray physics, dosimetry, radioprotection, hadron therapy, space radiation, accelerator design and neutronics. The code is the standard tool used at CERN for dosimetry, radioprotection and beam-machine interaction studies. Here we give a glimpse into the code physics models with a particular emphasis to the hadronic and nuclear sector.

  8. PREFACE: Scientific Organising Committee Information

    NASA Astrophysics Data System (ADS)

    2015-06-01

    Edited by: Oliver Roberts Lorraine Hanlon Sheila McBreen Local Organising Committee: Oliver Roberts (Chair) Antonio Martin-Carrillo Lorraine Hanlon Sheila McBreen Alexey Uliyanov David Murphy Sinéad Hales Scientific Organising Committee:: Sheila McBreen, (UCD, Ireland) (Chair) Franco Camera (INFN-Milano, Italy) Nerine Cherepy (LLNL, USA) Jarek Glodo (RMD, USA) Lorraine Hanlon (UCD, Ireland) Paul Lecoq (CERN, Switzerland) Julie McEnery (NASA, USA) Oliver Roberts (UCD, Ireland) Anant Setlur, (GE, USA) Brian Shortt, (ESA, the Netherlands) Kenneth Stanton (UCD, Ireland)

  9. The design of the optical modules of the KM3NeT-Italia project towers

    NASA Astrophysics Data System (ADS)

    Leonora, Emanuele; Aiello, Sebastiano; Giordano, Valentina

    2016-07-01

    The KM3NeT-Italia project aims to construct a large volume underwater neutrino telescope, to be installed in the depths of the Mediterranean Sea. The R&D and mass production phases of the detection elements of the telescope, the optical modules, were entirely performed in the INFN-LNS site in the harbour of Catania. In November 2014 a first tower of 14 storeys equipped with 84 optical modules was successfully deployed in the Mediterranean Sea site. The design of the optical modules and their main components are described in this paper.

  10. ({sup 18}O,{sup 18}Ne) double charge-exchange with MAGNEX

    SciTech Connect

    Bondí, M.; Cappuzzello, F.; Nicolosi, D.; Tropea, S.; Agodi, C.; Carbone, D.; Cavallaro, M.; Cunsolo, A.; De Napoli, M.; Foti, A.

    2014-05-09

    An experimental study concerning Double Gamow-Teller (DGT) modes in ({sup 18}O,{sup 18}Ne) Double Charge-Exchange reactions has been very recently performed at INFN-LNS laboratory in Catania. The experiment was performed using a {sup 40}Ca solid target and a {sup 18}O Cyclotron beam at 270 MeV incident energy. Charged ejectiles produced in the reaction were momentum analyzed and identified by MAGNEX spectrometer at very forward angles. Preliminary results are presented in the present paper.

  11. A SINGLE-EXPOSURE, MULTIDETECTOR NEUTRON SPECTROMETER FOR WORKPLACE MONITORING.

    PubMed

    Bedogni, R; Bortot, D; Buonomo, B; Esposito, A; Gómez-Ros, J M; Introini, M V; Mazzitelli, G; Moraleda, M; Pola, A; Romero, A M

    2016-09-01

    This communication describes a recently developed single-exposure neutron spectrometer, based on multiple active thermal neutron detectors located within a moderating sphere, which have been developed jointly by CIEMAT (Spain), INFN (Italy) and Politecnico di Milano (Italy) in the framework of Italian and Spanish collaboration projects. The fabricated prototypes permit to achieve spectrometric resolution with nearly isotropic response for neutron with energies from thermal to 100-200 MeV, thus being able to characterise the complete neutron spectrum in only one exposure by unfolding the measured responses of the detectors. This makes it especially advantageous for characterising neutron fields and workplace monitoring purposes in neutron-producing facilities.

  12. The new hybrid thermal neutron facility at TAPIRO reactor for BNCT radiobiological experiments.

    PubMed

    Esposito, J; Rosi, G; Agosteo, S

    2007-01-01

    A new thermal neutron irradiation facility, devoted to carry out both dosimetric and radiobiological studies on boron carriers, which are being developed in the framework of INFN BNCT project, has been installed at the ENEA Casaccia TAPIRO research fast reactor. The thermal column, based on an original, hybrid, neutron spectrum shifter configuration, has been recently become operative. In spite of its low power (5 kW), the new facility is able to provide a high thermal neutron flux level, uniformly distributed inside the irradiation cavity, with a quite low gamma background. The main features and preliminary benchmark measurements of the Beam-shaping assembly are here presented and discussed.

  13. The new hybrid thermal neutron facility at TAPIRO reactor for BNCT radiobiological experiments.

    PubMed

    Esposito, J; Rosi, G; Agosteo, S

    2007-01-01

    A new thermal neutron irradiation facility, devoted to carry out both dosimetric and radiobiological studies on boron carriers, which are being developed in the framework of INFN BNCT project, has been installed at the ENEA Casaccia TAPIRO research fast reactor. The thermal column, based on an original, hybrid, neutron spectrum shifter configuration, has been recently become operative. In spite of its low power (5 kW), the new facility is able to provide a high thermal neutron flux level, uniformly distributed inside the irradiation cavity, with a quite low gamma background. The main features and preliminary benchmark measurements of the Beam-shaping assembly are here presented and discussed. PMID:17504745

  14. PREFACE: Nanoscale science and technology

    NASA Astrophysics Data System (ADS)

    Bellucci, Stefano

    2008-11-01

    Over the last decade, rapid progress in the field of nanoscience has been increasingly driving the attention of the scientific community as well as society at large on the corresponding technological applications, which are the object of so-called nanotechnology. A strong interest in assessing the current state of the art of this fast growing field, as well as stimulating research networking, prompted the organization of the International School and Workshop 'Nanoscience & Nanotechnology (n&n2007)', under the patronage of the Italian Institute for Nuclear Physics (INFN), the University of Rome Tor Vergata, the Tor Vergata Polyclinic, and the Catholic University of Rome, with generous sponsorship from 3M, 2M Strumenti, MTS, Ape Research, Crisel Instruments, Veeco and Amira. The aims of this event were as follows: to foster the concrete planning of future devices based on innovative (nano)materials, involving both industrial entities and public research institutes; to allow sponsoring firms to present their instrumentation and success stories, based on current use by significant customers; to lend an opportunity for preparing and presenting joint projects, involving both industry and public research, see e.g. the EU 7th Framework Programs; to explore the possibility of integrating nanodevices from their concept into system projects. The conference http://www.lnf.infn.it/conference/nn2007/ gathered at Villa Mondragone in Monte Porzio Catone, Italy, with leading experts in research and innovative technologies in biology, medicine, aerospace, optoelectronics, materials and instrumentation, coming both from academic research and industrial areas, as well as national security and military defense experts in attendence. Several successful meetings in this field have taken place in the past, such as the Nanotubes & Nanostructures (N&N) School and Workshop Series [1, 2, 3, 4] including: N&N2000, S Margherita di Pula (Cagliari), Italy, 24 September-4 October 2000, http://www.lnf.infn

  15. Proton therapy detector studies under the experience gained at the CATANA facility

    NASA Astrophysics Data System (ADS)

    Cuttone, G.; Cirrone, G. A. P.; Di Rosa, F.; Lojacono, P. A.; Lo Nigro, S.; Marino, C.; Mongelli, V.; Patti, I. V.; Pittera, S.; Raffaele, L.; Russo, G.; Sabini, M. G.; Salamone, V.; Valastro, L. M.

    2007-10-01

    Proton therapy represents the most promising radiotherapy technique for external tumor treatments. At Laboratori Nazionali del Sud of the Istituto Nazionale di Fisica Nucleare (INFN-LNS), Catania (I), a proton therapy facility is active since March 2002 and 140 patients, mainly affected by choroidal and iris melanoma, have been successfully treated. Proton beams are characterized by higher dose gradients and linear energy transfer with respect to the conventional photon and electron beams, commonly used in medical centers for radiotherapy.In this paper, we report the experience gained in the characterization of different dosimetric systems, studied and/or developed during the last ten years in our proton therapy facility.

  16. A grassmannian formulation of the WZW and minimal models

    NASA Astrophysics Data System (ADS)

    Fucito, Francesco

    1989-05-01

    Grassmannians provide a geometrical interpretation of infinite dimensional Kac-Moody and Virasoro algebras. Here we show how to obtain, using this formulism, the values of the central charges and the conformal dimensions (weights) corresponding to the WZW and minimal models. This is achieved by suitably generalizing the procedure which gave the central charge and the conformal dimension of the b-c system. In analogy with this previous case we get a prescription to compute the correlation functions of such models on Riemann surfaces of arbitrary genus. On leave of absence from Dipartimento di Fisica, INFN- Sezione di Roma, Universitá di Roma II, ``Tor Vergata'', I-00173 Rome, Italy.

  17. Combined Use of Etomidate and Dexmedetomidine Produces an Additive Effect in Inhibiting the Secretion of Human Adrenocortical Hormones

    PubMed Central

    Gu, Hongbin; Zhang, Mazhong; Cai, Meihua; Liu, Jinfen

    2015-01-01

    Background The direct effects of etomidate were investigated on the secretion of cortisol and its precursors by dispersed cells from the adrenal cortex of human of animals. Dexmedetomidine (DEX) is an anesthetic agent that may interfere with cortisol secretion via an unknown mechanism, such as involving inhibition of 11β-hydroxylase and the cholesterol side-chain cleavage enzyme system. The aim of this study was to determine whether dexmedetomidine (DEX) has a similar inhibitory effect on adrenocortical function, and whether combined use of etomidate (ETO) and DEX could produce a synergistic action in inhibiting the secretion of human adrenocortical hormones. Material/Methods Human adrenocortical cells were exposed to different concentrations of ETO and DEX. The dose-effect model between the ETO concentration and the mean secretion of cortisone (CORT) and aldosterone (ALDO) per hour was estimated. Results Hill’s equation well-described the dose-effect correlation between the ETO concentration and the amount of ALDO and CORT secretion. When the DEX concentration was introduced into the model by using E0 (basal secretion) as the covariate, the goodness of fit of the ETO-CORT dose-effect model was improved significantly and the objective function value was reduced by 4.55 points (P<0.05). The parameters of the final ETO-ALDO pharmacodynamics model were EC50=9.74, Emax=1.20, E0=1.33, and γ=18.5; the parameters of the final ETO-CORT pharmacodynamics model were EC50=9.49, Emax=8.16, E0=8.57, and γ=37.0. In the presence of DEX, E0 was 8.57–0.0247×(CDEX–4.6), and the other parameters remained unchanged. All parameters but γ were natural logarithm conversion values. Conclusions Combined use of DEX and ETO reduced ETO’s inhibitory E0 (basal secretion) of CORT from human adrenocortical cells in a dose-dependent manner, suggesting that combined use of ETO and DEX produced an additive effect in inhibiting the secretion of human adrenocortical hormones. PMID

  18. Fundamental roles of reactive oxygen species and protective mechanisms in the female reproductive system

    PubMed Central

    Fujii, Junichi; Iuchi, Yoshihito; Okada, Futoshi

    2005-01-01

    Controlled oxidation, such as disulfide bond formation in sperm nuclei and during ovulation, plays a fundamental role in mammalian reproduction. Excess oxidation, however, causes oxidative stress, resulting in the dysfunction of the reproductive process. Antioxidation reactions that reduce the levels of reactive oxygen species are of prime importance in reproductive systems in maintaining the quality of gametes and support reproduction. While anti-oxidative enzymes, such as superoxide dismutase and peroxidase, play a central role in eliminating oxidative stress, reduction-oxidation (redox) systems, comprised of mainly glutathione and thioredoxin, function to reduce the levels of oxidized molecules. Aldo-keto reductase, using NADPH as an electron donor, detoxifies carbonyl compounds resulting from the oxidation of lipids and proteins. Thus, many antioxidative and redox enzyme genes are expressed and aggressively protect gametes and embryos in reproductive systems. PMID:16137335

  19. Crystallization and preliminary X-ray diffraction analysis of mouse prostaglandin F2α synthase, AKR1B3

    PubMed Central

    Takashima, Yasuhide; Hatanaka, Seika; Mizohata, Eiichi; Nagata, Nanae; Fukunishi, Yoshifumi; Matsumura, Hiroyoshi; Urade, Yoshihiro; Inoue, Tsuyoshi

    2011-01-01

    Aldo-keto reductase 1B3 (AKR1B3) catalyzes the NADPH-dependent reduction of prostaglandin H2 (PGH2), which is a common intermediate of various prostanoids, to form PGF2α. AKR1B3 also reduces PGH2 to PGD2 in the absence of NADPH. AKR1B3 produced in Escherichia coli was crystallized in complex with NADPH by the sitting-drop vapour-diffusion method. The crystal was tetragonal, belonging to space group P41212 or P43212, with unit-cell parameters a = b = 107.62, c = 120.76 Å. X-ray diffraction data were collected to 2.4 Å resolution at 100 K using a synchrotron-radiation source. PMID:22139184

  20. Luna B. Leopold--pioneer setting the stage for modern hydrology

    USGS Publications Warehouse

    Hunt, Randall J.; Meine, Curt

    2012-01-01

    In 1986, during the first year of graduate school, the lead author was sampling the water from a pitcher pump in front of “The Shack,” the setting of the opening essays in Aldo Leopold's renowned book A Sand County Almanac. The sampling was part of my Master's work that included quarterly monitoring of water quality on the Leopold Memorial Reserve (LMR) near Baraboo, Wisconsin. The Shack was already a well-known landmark, and it was common to come upon visitors and hikers there. As such, I took no special note of the man who approached me as I was filling sample bottles and asked, as was typical, “What are you doing?”

  1. Design and synthesis of polyhydroxy steroids as selective inhibitors against AKR1B10 and molecular docking.

    PubMed

    Chen, Wenli; Chen, Xinying; Zhou, Shujia; Zhang, Hong; Wang, Ling; Xu, Jun; Hu, Xiaopeng; Yin, Wei; Yan, Guangmei; Zhang, Jingxia

    2016-06-01

    AKR1B10 is a member of the human aldo-keto reductase superfamily which is highly expressed in several types of cancers, and has been regarded as a promising cancer therapeutic target. In this paper, a series of polyhydroxy steroids were designed and synthesized to selectively inhibit AKR1B10 activity. The most selective compound, novel compound 6, has an IC50 of 0.83±0.07μM and a selectivity of more than 120-fold for AKR1B10/AKR1B1. Structure-activity relation analyses indicate that hydroxyl at C-19 can significantly improve the selective inhibition of AKR1B10. The binding mode of AKR1B10 and its inhibitors were studied.

  2. Selective AKR1C3 Inhibitors Potentiate Chemotherapeutic Activity in Multiple Acute Myeloid Leukemia (AML) Cell Lines.

    PubMed

    Verma, Kshitij; Zang, Tianzhu; Gupta, Nehal; Penning, Trevor M; Trippier, Paul C

    2016-08-11

    We report the design, synthesis, and evaluation of potent and selective inhibitors of aldo-keto reductase 1C3 (AKR1C3), an important enzyme in the regulatory pathway controlling proliferation, differentiation, and apoptosis in myeloid cells. Combination treatment with the nontoxic AKR1C3 inhibitors and etoposide or daunorubicin in acute myeloid leukemia cell lines, elicits a potent adjuvant effect, potentiating the cytotoxicity of etoposide by up to 6.25-fold and the cytotoxicity of daunorubicin by >10-fold. The results validate AKR1C3 inhibition as a common adjuvant target across multiple AML subtypes. These compounds in coadministration with chemotherapeutics in clinical use enhance therapeutic index and may avail chemotherapy as a treatment option to the pediatric and geriatric population currently unable to tolerate the side effects of cancer drug regimens. PMID:27563402

  3. Crystallization and preliminary X-ray diffraction analysis of maize aldose reductase

    SciTech Connect

    Kiyota, Eduardo; Sousa, Sylvia Morais de; Santos, Marcelo Leite dos; Costa Lima, Aline da; Menossi, Marcelo; Yunes, José Andrés; Aparicio, Ricardo

    2007-11-01

    Preliminary X-ray diffraction studies of apo maize aldose reductase at 2.0 Å resolution are reported. Maize aldose reductase (AR) is a member of the aldo-keto reductase superfamily. In contrast to human AR, maize AR seems to prefer the conversion of sorbitol into glucose. The apoenzyme was crystallized in space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 47.2, b = 54.5, c = 100.6 Å and one molecule in the asymmetric unit. Synchrotron X-ray diffraction data were collected and a final resolution limit of 2.0 Å was obtained after data reduction. Phasing was carried out by an automated molecular-replacement procedure and structural refinement is currently in progress. The refined structure is expected to shed light on the functional/enzymatic mechanism and the unusual activities of maize AR.

  4. Plant science. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein.

    PubMed

    Winzer, Thilo; Kern, Marcelo; King, Andrew J; Larson, Tony R; Teodor, Roxana I; Donninger, Samantha L; Li, Yi; Dowle, Adam A; Cartwright, Jared; Bates, Rachel; Ashford, David; Thomas, Jerry; Walker, Carol; Bowser, Tim A; Graham, Ian A

    2015-07-17

    Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.

  5. Effect of amiloride and spironolactone on renal tubular function, ambulatory blood pressure, and pulse wave velocity in healthy participants in a double-blinded, randomized, placebo-controlled, crossover trial.

    PubMed

    Matthesen, Solveig Klok; Larsen, Thomas; Lauridsen, Thomas Guldager; Vase, Henrik; Gjørup, Pia Holland; Nykjær, Karen Marie; Nielsen, Søren; Pedersen, Erling Bjerregaard

    2012-01-01

    We wanted to test the hypothesis that treatment with amiloride or spironolactone reduced ambulatory (ABP) and central blood pressure (CBP) and that tubular transport via ENaCγ and AQP2 was increased after furosemide treatment. During baseline conditions, there were no differences in ABP, CBP, renal tubular function, or plasma concentrations of vasoactive hormones. After furosemide treatment, an increase in CBP, CH(2)o, FE(Na), FE(K), u-AQP2/min, u-ENaCγ/min, PRC, p-Ang II, and p-Aldo was observed. The increases in water and sodium absorption via AQP2 and ENaC after furosemide treatment most likely are compensatory phenomena to antagonize water and sodium depletion. PMID:22591021

  6. Kinetics and mechanism of oxidation of erythro-series pentoses and hexoses by N-chloro-p-toluenesulfonamide.

    PubMed

    Rangappa, K S; Raghavendra, M P; Mahadevappa, D S; Gowda, D C

    1998-01-01

    The kinetics and mechanism of oxidation of D-glucose, D-mannose, D-fructose, D-arabinose, and D-ribose with chloramine-T in alkaline medium were studied. The rate law, rate = k [Chloramine-T] [Sugar] [HO-]2, was observed. The rate of the reaction was influenced by a change in ionic strength of the medium, and the dielectric effect was found to be negative. The latter enabled the computation of dAB, the size of the activated complex. The reaction rate was almost doubled in deuterium oxide. Activation energies were calculated from the Arrhenius plots. HPLC and GLC-MS analyses of the products indicated that the sugars were oxidized to a mixture of aldonic acids, consisting of arabinonic, ribonic, erythronic, and glyceric acids. Based on these data, a plausible mechanism involving the aldo-enolic anions of pentoses and keto-enolic anions of hexoses is suggested.

  7. Cold acclimation induced genes of trifoliate orange (Poncirus trifoliata).

    PubMed

    Zhang, Can-kui; Lang, Ping; Dane, Fenny; Ebel, Robert C; Singh, Narendra K; Locy, Robert D; Dozier, William A

    2005-03-01

    Commercial citrus varieties are sensitive to low temperature. Poncirus trifoliata is a close relative of Citrus species and has been widely used as a cold-hardy rootstock for citrus production in low-temperature environments. mRNA differential display-reverse transcription (DDRT)-PCR and quantitative relative-RT-PCR were used to study gene expression of P. trifoliata under a gradual cold-acclimation temperature regime. Eight up-regulated cDNA fragments were isolated and sequenced. These fragments showed high similarities at the amino acid level to the following genes with known functions: betaine/proline transporter, water channel protein, aldo-keto reductase, early light-induced protein, nitrate transporter, tetratricopeptide-repeat protein, F-box protein, and ribosomal protein L15. These cold-acclimation up-regulated genes in P. trifoliata are also regulated by osmotic and photo-oxidative signals in other plants.

  8. Plant science. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein.

    PubMed

    Winzer, Thilo; Kern, Marcelo; King, Andrew J; Larson, Tony R; Teodor, Roxana I; Donninger, Samantha L; Li, Yi; Dowle, Adam A; Cartwright, Jared; Bates, Rachel; Ashford, David; Thomas, Jerry; Walker, Carol; Bowser, Tim A; Graham, Ian A

    2015-07-17

    Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production. PMID:26113639

  9. A comparative proteomic analysis of Bacillus coagulans in response to lactate stress during the production of L-lactic acid.

    PubMed

    Wang, Xiuwen; Qin, Jiayang; Wang, Landong; Xu, Ping

    2014-12-01

    The growth rate and maximum biomass of Bacillus coagulans 2-6 were inhibited by lactate; inhibition by sodium lactate was stronger than by calcium lactate. The differences of protein expressions by B. coagulans 2-6 under the lactate stress were determined using two-dimensional electrophoresis coupled with mass spectrometric identification. Under the non-stress condition, calcium lactate stress and sodium lactate stress, the number of detected protein spots was 1,571 ± 117, 1,281 ± 231 and 904 ± 127, respectively. Four proteins with high expression under lactate stress were identified: lactate dehydrogenase, cysteine synthase A, aldo/keto reductase and ribosomal protein L7/L12. These proteins are thus potential targets for the reconstruction of B. coagulans to promote its resistance to lactate stress.

  10. Hook effect: a pitfall leading to misdiagnosis of hypoaldosteronism in an infant with pseudohypoaldosteronism.

    PubMed

    Akin, Leyla; Kurtoglu, Selim; Kendirci, Mustafa; Akin, Mustafa Ali; Hartmann, Michaela F; Wudy, Stefan A

    2010-01-01

    We report herein the case of a premature infant who presented with failure to thrive, hyponatremia, hyperkalemia and metabolic acidosis. Initial serum hormone profiling suggested isolated hypoaldosteronism (aldosterone: 0.01 pg/ml, normal range: 50-900 pg/ml). A gas chromatography-mass spectrometry spot urinary steroid profile showed grossly elevated levels of 18-hydroxy-tetrahydro-11-dehydrocorticosterone (18-hydroxy-THA: 5,893 microg/l; normal upper limit 36 microg/l) and tetrahydroaldosterone (TH-Aldo: 5,749 microg/l; normal upper limit 36 microg/l) which are aldosterone precursor metabolite and aldosterone metabolite, respectively. Thus, aldosterone synthase deficiency was excluded and pseudohypoaldosteronism (PHA) was suggested. A repeated test after dilution of the serum revealed a very high level of aldosterone (6,490 pg/ml), confirming the diagnosis of PHA in this case.

  11. The C-terminal loop of aldehyde reductase determines the substrate and inhibitor specificity.

    PubMed

    Barski, O A; Gabbay, K H; Bohren, K M

    1996-11-12

    Human aldehyde reductase has a preference for carboxyl group-containing negatively charged substrates. It belongs to the NADPH-dependent aldo-keto reductase superfamily whose members are in part distinguished by unique C-terminal loops. To probe the role of the C-terminal loops in determining substrate specificities in these enzymes, two arginine residues, Arg308 and Arg311, located in the C-terminal loop of aldehyde reductase, and not found in any other C-terminal loop, were replaced with alanine residues. The catalytic efficiency of the R311A mutant for aldehydes containing a carboxyl group is reduced 150-250-fold in comparison to that of the wild-type enzyme, while substrates not containing a negative charge are unaffected. The R311A mutant is also significantly less sensitive to inhibition by dicarboxylic acids, indicating that Arg311 interacts with one of the carboxyl groups. The inhibition pattern indicates that the other carboxyl group binds to the anion binding site formed by Tyr49, His112, and the nicotinamide moiety of NADP+. The correlation between inhibitor potency and the length of the dicarboxylic acid molecules suggests a distance of approximately 10 A between the amino group of Arg311 and the anion binding site in the aldehyde reductase molecule. The sensitivity of inhibition of the R311A mutant by several commercially available aldose reductase inhibitors (ARIs) was variable, with tolrestat and zopolrestat becoming more potent inhibitors (30- and 5-fold, respectively), while others remained the same or became less potent. The catalytic properties, substrate specificity, and susceptibility to inhibition of the R308A mutant remained similar to that of the wild-type enzyme. The data provide direct evidence for C-terminal loop participation in determining substrate and inhibitor specificity of aldo-keto reductases and specifically identifies Arg311 as the basis for the carboxyl-containing substrate preference of aldehyde reductase. PMID:8916913

  12. Temporal dissociation between sodium depletion and sodium appetite appearance: Involvement of inhibitory and stimulatory signals.

    PubMed

    Margatho, L O; Porcari, C Y; Macchione, A F; da Silva Souza, G D; Caeiro, X E; Antunes-Rodrigues, J; Vivas, L; Godino, A

    2015-06-25

    Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2h vs. 24h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2h vs. 24h after PD. Additionally, we combined the analysis of brain Fos immunoreactivity (Fos-ir) with the detection of double immunoreactivity in 5HT and oxytocinergic (OT) cells 2h after PD. Bilateral LPBN injections of methysergide (4μg/200nl at each site) increased NaCl intake when tested 2h after PD compared to controls. We found a significant increase in PRA and ALDO concentration after PD but no differences between 2 and 24h after PD. We also found for the first time a significant increase 2h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal. PMID:25841323

  13. Plant tropane alkaloid biosynthesis evolved independently in the Solanaceae and Erythroxylaceae.

    PubMed

    Jirschitzka, Jan; Schmidt, Gregor W; Reichelt, Michael; Schneider, Bernd; Gershenzon, Jonathan; D'Auria, John Charles

    2012-06-26

    The pharmacologically important tropane alkaloids have a scattered distribution among angiosperm families, like many other groups of secondary metabolites. To determine whether tropane alkaloids have evolved repeatedly in different lineages or arise from an ancestral pathway that has been lost in most lines, we investigated the tropinone-reduction step of their biosynthesis. In species of the Solanaceae, which produce compounds such as atropine and scopolamine, this reaction is known to be catalyzed by enzymes of the short-chain dehydrogenase/reductase family. However, in Erythroxylum coca (Erythroxylaceae), which accumulates cocaine and other tropane alkaloids, no proteins of the short-chain dehydrogenase/reductase family were found that could catalyze this reaction. Instead, purification of E. coca tropinone-reduction activity and cloning of the corresponding gene revealed that a protein of the aldo-keto reductase family carries out this reaction in E. coca. This protein, designated methylecgonone reductase, converts methylecgonone to methylecgonine, the penultimate step in cocaine biosynthesis. The protein has highest sequence similarity to other aldo-keto reductases, such as chalcone reductase, an enzyme of flavonoid biosynthesis, and codeinone reductase, an enzyme of morphine alkaloid biosynthesis. Methylecgonone reductase reduces methylecgonone (2-carbomethoxy-3-tropinone) stereospecifically to 2-carbomethoxy-3β-tropine (methylecgonine), and has its highest activity, protein level, and gene transcript level in young, expanding leaves of E. coca. This enzyme is not found at all in root tissues, which are the site of tropane alkaloid biosynthesis in the Solanaceae. This evidence supports the theory that the ability to produce tropane alkaloids has arisen more than once during the evolution of the angiosperms.

  14. Interdisciplinary Adventures in Perceptual Ecology

    NASA Astrophysics Data System (ADS)

    Bocast, Christopher S.

    A portfolio dissertation that began as acoustic ecology and matured into perceptual ecology, centered on ecomusicology, bioacoustics, and translational audio-based media works with environmental perspectives. The place of music in Western eco-cosmology through time provides a basis for structuring an environmental history of human sound perception. That history suggests that music may stabilize human mental activity, and that an increased musical practice may be essential for the human project. An overview of recent antecedents preceding the emergence of acoustic ecology reveals structural foundations from 20th century culture that underpin modern sound studies. The contextual role that Aldo Leopold, Jacob von Uexkull, John Cage, Marshall McLuhan, and others played in anticipating the development of acoustic ecology as an interdiscipline is detailed. This interdisciplinary aspect of acoustic ecology is defined and defended, while new developments like soundscape ecology are addressed, though ultimately sound studies will need to embrace a broader concept of full-spectrum "sensory" or "perceptual" ecology. The bioacoustic fieldwork done on spawning sturgeon emphasized this necessity. That study yielded scientific recordings and spectrographic analyses of spawning sounds produced by lake sturgeon, Acipenser fulvescens, during reproduction in natural habitats in the Lake Winnebago watershed in Wisconsin. Recordings were made on the Wolf and Embarrass River during the 2011-2013 spawning seasons. Several specimens were dissected to investigate possible sound production mechanisms; no sonic musculature was found. Drumming sounds, ranging from 5 to 7 Hz fundamental frequency, verified the infrasonic nature of previously undocumented "sturgeon thunder". Other characteristic noises of sturgeon spawning including low-frequency rumbles and hydrodynamic sounds were identified. Intriguingly, high-frequency signals resembling electric organ discharges were discovered. These

  15. New inhibitors of the Kvβ2 subunit from mammalian Kv1 potassium channels.

    PubMed

    Alka, Kumari; Dolly, J Oliver; Ryan, Barry J; Henehan, Gary T M

    2014-10-01

    The role of the redox state of Kvβ subunits in the modulation of Kv1 potassium channels has been well documented over the past few years. It has been suggested that a molecule that binds to or inhibits the aldo-keto reductase activity of Kvβ might affect the modulation of channel properties. Previous studies of possible modulators of channel activity have shown that cortisone and some related compounds are able to physically dissociate the channel components by binding to a site at the interface between α and β subunits. Herein, we describe some new inhibitors of rat brain Kvβ2, identified using an assay based on multiple substrate turnover. This approach allows one to focus on molecules that specifically block NADPH oxidation. These studies showed that, at 0.5mM, 3,4-dihydroxphenylacetic acid (DOPAC) was an inhibitor of Kvβ2 turnover yielding a ∼ 40-50% reduction in the aldehyde reductase activity of this subunit. Other significant inhibitors include the bioflavinoid, rutin and the polyphenol resveratrol; some of the known cardioprotective effects of these molecules may be attributable to Kv1 channel modulation. Cortisone or catechol caused moderate inhibition of Kvβ2 turnover, and the aldo-keto reductases inhibitor valproate had an even smaller effect. Despite the importance of the Kv1 channels in a number of disease states, there have been few Kvβ2 inhibitors reported. While the ones identified in this study are only effective at high concentrations, they could serve as tools to decipher the role of Kvβ2 in vivo and, eventually, inform the development of novel therapeutics.

  16. Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

    PubMed Central

    Gehrand, Ashley; Bruder, Eric D.; Hoffman, Matthew J.; Engeland, William C.; Moreno, Carol

    2014-01-01

    The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo (Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland. PMID:25394830

  17. Transforming growth factor-beta-dependent and -independent pathways of induction of tubulointerstitial fibrosis in beta6(-/-) mice.

    PubMed

    Ma, Li-Jun; Yang, Haichun; Gaspert, Ariana; Carlesso, Gianluca; Barty, Melissa M; Davidson, Jeffrey M; Sheppard, Dean; Fogo, Agnes B

    2003-10-01

    Transforming growth factor-beta1 (TGF-beta1) and the renin-angiotensin-aldosterone system are key mediators in kidney fibrosis. Integrin alphavbeta6, a heterodimeric matrix receptor expressed in epithelia, binds and activates latent TGF-beta1. We used beta6 integrin-null mice (beta6(-/-)) to determine the role of local TGF-beta1 activation in renal fibrosis in the unilateral ureteral obstruction (UUO) model. Obstructed kidneys from beta6(-/-) mice showed less injury than obstructed kidneys from wild-type (WT) mice, associated with lower collagen I, collagen III, plasminogen activator inhibitor (PAI-1), and TGF-beta1 mRNA levels and lower collagen content. Infusion with either angiotensin II (Ang II) or aldosterone (Aldo) or combination in beta6(-/-) UUO mice significantly increased collagen contents to levels comparable to those in identically treated WT. Active TGF-beta protein expression in beta6(-/-) mice was less in UUO kidneys with or without Ang II infusion compared to matched WT mice. Activated Smad 2 levels in beta6(-/-) obstructed kidneys were lower than in WT UUO mice, and did not increase when fibrosis was induced in beta6(-/-) UUO mice by Ang II infusion. Anti-TGF-beta antibody only partially decreased this Ang II-stimulated fibrosis in beta6(-/-) UUO kidneys. In situ hybridization and immunostaining showed low expression of PAI-1 mRNA and protein in tubular epithelium in beta6(-/-) UUO kidneys, with increased PAI-1 expression in response to Ang II, Aldo, or both. Our results indicate that interruption of alphavbeta6-mediated activation of TGF-beta1 can protect against tubulointerstitial fibrosis. Further, the robust induction of tubulointerstitial fibrosis without increase in activated Smad 2 levels in obstructed beta6(-/-) mice by Ang II suggests the existence of a TGF-beta1-independent pathway of induction of fibrosis through angiotensin.

  18. Spes: Exotic Beams for Nuclear Physics Studies

    NASA Astrophysics Data System (ADS)

    Andrighetto, Alberto; Manzolaro, Mattia; Corradetti, Stefano; Scarpa, Daniele; Vasquez, Jesu; Rossignoli, Massimo; Monetti, Alberto; Calderolla, Michele; Prete, Gianfranco

    2014-02-01

    The SPES project at Laboratori di Legnaro of INFN (Italy) is concentrating on the production of neutron-rich radioactive nuclei for nuclear physics experiments using uranium fission at a rate of 1013 fission/s. The emphasis on neutron-rich isotopes is justified by the fact that this vast territory has been little explored. The Radioactive Ion Beam (RIB) will be produced by the ISOL technique using proton induced fission on a direct target of UCx. The most critical element of the SPES project is the Multi-Foil Direct Target. Up to the present time, the proposed target represents an innovation in terms of its capability to sustain the primary beam power. This talk will present the status of the project financed by INFN, which is actually in the construction phase at Legnaro. In particular, developments related to the target and the ion-source activities using the surface ion source, plasma ion source, and laser ion source techniques will be reported.

  19. Design of the ELIMAIA ion collection system

    NASA Astrophysics Data System (ADS)

    Schillaci, F.; Cirrone, G. A. P.; Cuttone, G.; Maggiore, M.; Andó, L.; Amato, A.; Costa, M.; Gallo, G.; Korn, G.; Larosa, G.; Leanza, R.; Manna, R.; Margarone, D.; Milluzzo, G.; Pulvirenti, S.; Romano, F.; Salamone, S.; Sedita, M.; Scuderi, V.; Tramontana, A.

    2015-12-01

    A system of permanent magnet quadrupoles (PMQs) is going to be realized by INFN-LNS to be used as a collection system for the injection of laser driven ion beams up to 60 MeV/u in an energy selector based on four resistive dipoles. This system is the first element of the ELIMED (ELI-Beamlines MEDical and Multidisciplinary applications) beam transport, dosimetry and irradiation line that will be developed by INFN-LNS (It) and installed at the ELI-Beamlines facility in Prague (Cz). ELIMED will be the first user's open transport beam-line where a controlled laser-driven ion beam will be used for multidisciplinary researches. The definition of well specified characteristics, both in terms of performances and field quality, of the magnetic lenses is crucial for the system realization, for the accurate study of the beam dynamics and for the proper matching with the magnetic selection system which will be designed in the next months. Here, we report the design of the collection system and the adopted solutions in order to realize a robust system form the magnetic point of view. Moreover, the first preliminary transport simulations are also described.

  20. Editorial

    NASA Astrophysics Data System (ADS)

    Bruzzi, Mara; Pace, Emanuele; Talamonti, Cinzia

    2013-12-01

    The 9th edition of the International Conference on Radiation Effects on Semiconductor Materials, Detectors and Devices (RESMDD), held in Florence, at Dipartimento di Fisica ed Astronomia on October 9-12, 2012, was aimed at discussing frontier research activities in several application fields as in nuclear and particle physics, astrophysics, medical and solid-state physics. Main topics discussed in this conference are tracking performance of heavily irradiated silicon detectors, developments required for the luminosity upgrade of the Large Hadron Collider (HL-LHC), radiation effects on semiconductor materials for medical (radiotherapy dosimeters, imaging devices), astrophysics (UV, X- and γ-ray detectors) and environmental applications, microscopic defect analysis of irradiated semiconductor materials and related radiation hardening technologies. On the first day the conference hosted a short course intended to introduce fundamentals in the development of semiconductor detectors for medical applications to graduate and PhD students, post-docs and young researchers, both engineers and physicists. Directors of the School were Prof. Marta Bucciolini of the University of Florence and INFN, Italy and Dr. Carlo Civinini, INFN Firenze, Italy. Emphasis was placed on the underlying physical principles, instrument design, factors affecting performance, and applications in both the clinical and preclinical applications. The School was attended by nearly 40 students/ young researchers. We warmly thank the Directors for organizing this interesting event and the professors and researchers who gave lessons, for sharing their experience and knowledge with the students.

  1. The C-Band accelerating structures for SPARC photoinjector energy upgrade

    NASA Astrophysics Data System (ADS)

    Alesini, D.; Boni, R.; Di Pirro, G.; Di Raddo, R.; Ferrario, M.; Gallo, A.; Lollo, V.; Marcellini, F.; Palumbo, L.; Spizzo, V.; Mostacci, A.; Campogiani, G.; Persichelli, S.; Enomoto, A.; Higo, T.; Kakihara, K.; Kamitani, T.; Matsumoto, S.; Sugimura, T.; Yokoyama, K.; Verdú-Andrés, S.

    2013-05-01

    The use of C-Band structures for electron acceleration and production of high quality beams has been proposed and adopted in several linac projects all over the world. The two main projects that adopted such type of structures are the Japanese Free Electron Laser (FEL) project in Spring-8 and the SwissFEL project at Paul Scherrer Institute (PSI). Also the energy upgrade of the SPARC photo-injector at LNF-INFN (Italy) from 150 to more than 240 MeV will be done by replacing a low gradient S-Band accelerating structure with two C-band structures. The structures are Traveling Wave (TW) and Constant Impedance (CI), have symmetric axial input couplers and have been optimized to work with a SLED RF input pulse. The paper presents the design criteria of the structures, the realization procedure and the low and high power RF test results on a prototype. The high power tests have been carried out by the Frascati INFN Laboratories in close collaboration with the Japanese Laboratory KEK. Experimental results confirmed the feasibility of the operation of the prototype at 50 MV/m with about 10-6 breakdowns per pulse per meter. Such high gradients have not been reached before in C-Band systems and demonstrated the possibility to use C-band accelerators, if needed, at such high field level. The results of the internal inspection of the structure after the high power test are also presented.

  2. Integrated thermal-optical simulations of a GNSS Retroreflector Array

    NASA Astrophysics Data System (ADS)

    Boni, A.; Cantone, C.; Dell'Agnello, S.; Ciocci, E.; Contessa, S.; Delle Monache, G. O.; Lops, C.; Maiello, M.; Martini, M.; Mondaini, C.; Patrizi, G.; Porcelli, L.; Salvatori, L.; Tibuzzi, M.; Tuscano, P.; Vittori, R.; Bianco, G.

    2015-07-01

    Satellite Laser Ranging (SLR) is one of the most precise and cost effective satellite positioning techniques, used for many years on geodetic, Earth observation and scientific satellites. In the last decades it has been applied on radio-navigation satellites as well, however still in a limited way. The benefits that such technique could bring to these satellites are many, but, in order to support at best their tracking, some improvements need to be done; one is the enhancement of optical response of SLR payloads throughout the orbit. INFN-LNF with the ASI-INFN project ETRUSCO-2 studied hardware and software solution to optimize the optical response of such payloads, with the design and fabrication of a GNSS Retroreflector Array (GRA). We simulated the performance of a model of the GRA in a specific orbit of Galileo, showing contained variation of optical intensity, approximately 5%, throughout the orbit. A comparison between two polarization states, linear and circular, proves how a circularly polarized beam could reduce, up to 3 times, intensity fluctuations at a fixed velocity aberration.

  3. Design, construction and tests of a 3 GHz proton linac booster (LIBO) for cancer therapy

    NASA Astrophysics Data System (ADS)

    Berra, Paolo

    2007-12-01

    In the last ten years the use of proton beams in radiation therapy has become a clinical tool for treatment of deep-seated tumours. LIBO is a RF compact and low cost proton linear accelerator (SCL type) for hadrontherapy. It is conceived by TERA Foundation as a 3 GHz Linac Booster, to be mounted downstream of an existing cyclotron in order to boost the energy of the proton beam up to 200 MeV, needed for deep treatment (~25 cm) in the human body. With this solution it is possible to transform a low energy commercial cyclotron, normally used for eye melanoma therapy, isotope production and nuclear physics research, into an accelerator for deep-seated tumours. A prototype module of LIBO has been built and successfully tested with full RF power at CERN and with proton beam at INFN Laboratori Nazionali del Sud (LNS) in Catania, within an international collaboration between TERA Foundation, CERN, the Universities and INFN groups of Milan and Naples. The mid-term aim of the project is the technology transfer of the accumulated know-how to a consortium of companies and to bring this novel medical tool to hospitals. The design, construction and tests of the LIBO prototype are described in detail.

  4. Radiation quality and ion-beam therapy: understanding the users' needs.

    PubMed

    Magrin, G; Mayer, R; Verona, C; Grevillot, Loïc

    2015-09-01

    Ion-beam therapy faces a growing demand of tools able to map radiation quality within the irradiated volume. Although analytical computations and simulations provide useful estimations of dose and radiation quality, the direct measure of those parameters would improve ion-beam therapy in particular when deep-seated tumours are irradiated, tissue composition and density are variable or organs at risk are near the tumour. Several ion-beam therapy facilities are studying detectors and procedures for measuring the radiation quality on a microdosimetric as well as a nanodosimetric scale. Simplicity and miniaturisation of the devices are essential for measurements first in phantoms and thereafter during therapy, particularly for intra-cavity detectors. MedAustron is studying solid-state detectors based on a single crystal chemical vapour deposition diamond. In collaboration with Italian National Institute for Nuclear Physics (INFN), Tor Vergata and Legnaro; INFN-microdosimetry and track structure project; Austrian Institute of Technology, Vienna; and Italian National agency for new technologies, energy and sustainable economic development, Rome, prototypes have been developed to characterise radiation quality in sizes equivalent to one micrometre of biological tissue. PMID:26180078

  5. PREFACE: International Symposium: Quasifission Process in Heavy Ion Reactions, Messina (Italy), November 8-9, 2010

    NASA Astrophysics Data System (ADS)

    2011-03-01

    Conference photograph Editors:Giorgio Giardina (University of Messina) Avazbek K Nasirov (Joint Institute for Nuclear Research) Sara Pirrone (Istituto Nazionale di Fisica Nucleare Sezione di Catania) Organizing Committee:Chairman: G Giardina (Messina - Italy)Co-Chairman: A K Nasirov (Dubna - Russia)Co-Chairman: S Pirrone (Catania - Italy)Scientific Secretary: G Mandaglio (Messina - Italy) and A Di Pietro (Catania - Italy) Organizing Institutions:University of Messina    Fondazione Bonino-Pulejo (Messina) University of Messina logo      PBP logo Topics: Capture and Deep Inelastic Collision Quasifission Complete Fusion Fast Fission Fusion-Fission Ternary Fission Synthesis of Heavy and Superheavy Elements Pre-equilibrium emission Local Organizing Committee:G Fazio (Messina), G Giardina (Messina), G Mandaglio (Messina), M Manganaro (Messina), M Romaniuk (Messina), C Saccà (Messina), A Di Pietro (Catania), S Pirrone (Catania), A Nasirov (Dubna) Sponsored by:University of Messina, Fondazione Bonino-Pulejo (Messina), INFN Sezione di Catania, INFN Laboratori Nazionali del Sud Catania. Website: http:/nucleo.unime.it/symp2010/

  6. New markers to identify the provenance of lapis lazuli: trace elements in pyrite by means of micro-PIXE

    NASA Astrophysics Data System (ADS)

    Re, A.; Angelici, D.; Lo Giudice, A.; Maupas, E.; Giuntini, L.; Calusi, S.; Gelli, N.; Massi, M.; Borghi, A.; Gallo, L. M.; Pratesi, G.; Mandò, P. A.

    2013-04-01

    Lapis lazuli has been used for glyptics and carving since the fifth millennium BC to produce jewels, amulets, seals, inlays, etc; the identification of the origin of the stone used for carving artworks may be valuable for reconstructing old trade routes. Since ancient lapis lazuli art objects are precious, only non-destructive techniques can be used to identify their provenance, and ion beam analysis (IBA) techniques allow us to characterise this stone in a fully non-invasive way. In addition, by using an ion microprobe, we have been able to focus the analysis on single crystals, as their typical dimensions may range from a few microns to hundreds of microns. Provenance markers, identified in previous IBA studies and already presented elsewhere, were based on the presence/absence of mineral phases, on the presence/quantity of trace elements inside a phase and on characteristic features of the luminescence spectra. In this work, a systematic study on pyrite crystals, a common accessory mineral in lapis lazuli, was carried out, following a multi-technique approach: optical microscopy and SEM-EDX to select crystals for successive trace element micro-PIXE measurements at two Italian facilities, the INFN Laboratori Nazionali di Legnaro and the INFN LABEC laboratory in Firenze. The results of this work allowed us to obtain new markers for lapis lazuli provenance identification.

  7. A new monitoring microsystem for radiation measurement based on VSLI technique

    NASA Astrophysics Data System (ADS)

    Cai, G.; Cerullo, N.; Martini, E.; Rancoita, P. G.; Riscossa, P.

    1997-02-01

    During the researches performed at CERN in high energy physics a new semiconductor gamma detector, based on VSLI electronics was developed at INFN. This device is little, cheap reliable and presents high performances. In the frame of a collaboration work, performed between DITEC, Ansaldo Ricerche, and INFN, was proposed, as possible, a new use of this detector, different from high energy experiments ,namely, the ``AVERAGE AXIAL POWER DISTRIBUTION MEASUREMENT IN A NUCLEAR FISSION REACTOR, USING MANY EX-CORE DETECTORS''. At present, the current PWR Ex-Core Nuclear Instrumentation System (NIS), is based on a detection facility, composed of four/six axial ionization chambas, each one of which monitors the ex-core neutron flux at one specific elevation. The new proposed Ex-core NIS concepts, is based on the presence of a large number of puntiform silicon detectors axially and radially arranged out of the Reactor Vessel and the concrete primary shield. The presence of a large number of detectors and the use of a fast charge preamplifier, connected to the silicon detectors (both of low cost), allows the use of a computer for on line direct control and protection system enhancing safety and economic characteristics of the nuclear reactor. In this paper, after description of the semiconductor detector, of the preamplifier, and of their performances, the above indicated application are described, stressing the safety and economics advantages to be reached through its use.

  8. A new monitoring microsystem for radiation measurement based on VSLI technique

    NASA Astrophysics Data System (ADS)

    Cai, G.; Cerullo, N.; Martini, E.; Rancoita, P. G.; Riscossa, P.

    1998-02-01

    During the researches performed at CERN in high energy physics a new semiconductor gamma detector, based on VSLI electronics was developed at INFN. This device is little, cheap reliable and presents high performances. In the frame of a collaboration work, performed between DITEC, Ansaldo Ricerche, and INFN, was proposed, as possible, a new use of this detector, different from high energy experiments, namely, the "AVERAGE AXIAL POWER DISTRIBUTION MEASUREMENT IN A NUCLEAR FISSION REACTOR, USING MANY EXCORE DETECTORS". At present, the current PWR Ex-Core Nuclear Instrumentation System (NIS), is based on a detection facility, composed of four/six axial ionization chambers, each one of which monitors the ex-core neutron flux at one specific elevation. The new proposed Ex-core NIS concepts, is based on the presence of a large number of puntiform silicon detectors axially and radially arranged out of the Reactor Vessel and the concrete primary shield. The presence of a large number of detectors and the use of a fast charge preamplifier, connected to the silicon detectors (both of low cost), allows the use of a computer for on line direct control and protection system enhancing safety and economic characteristics of the nuclear reactor. In this paper, after description of the semiconductor detector, of the preamplifier, and of their performances, the above indicated application are described, stressing the safety and economics advantages to be reached through its use.

  9. Recent results: Collider detector at Fermilab

    NASA Astrophysics Data System (ADS)

    1989-07-01

    The status and prospects of the 1988-1989 CDF data taking run with p¯p collisions at 1.8 TeV, are briefly reviewed. Results are presented on minimum-bias inelastic events from 1987 data at 1.8 and 0.63 TeV center of mass energy, and are compared with data at lower energy and with data from the CO experiment Transverse momentum spectra harden as the center of mass energy √s increases. Charged particle density in rapidity, and mean transverse momentum, increase faster than In(s). Charged particles frequently form jet-like clusters with transverse energy of a few GeV. The present CDF data do not permit conclusions for or against the possible formation of a quark gluon plasma. ANL-Brandeis-University of Chicago- Fermilab-INFN, Frascati-Harvard-University of Illinois-KEK-LBL-University of Pennsylvania-INFN, University and Scuole Nonnale, Pisa-Purdue- Rockefeller-Rutgers-Texas A&M-Tsukuba-University of Wisconsin

  10. Sperm whale assessment in the Western Ionian Sea using acoustic data from deep sea observatories

    NASA Astrophysics Data System (ADS)

    Caruso, Francesco; Bellia, Giorgio; Beranzoli, Laura; De Domenico, Emilio; Larosa, Giuseppina; Marinaro, Giuditta; Papale, Elena; Pavan, Gianni; Pellegrino, Carmelo; Pulvirenti, Sara; Riccobene, Giorgio; Scandura, Danila; Sciacca, Virginia; Viola, Salvatore

    2015-04-01

    The Italian National Institute of Nuclear Physics (INFN) operates two deep sea infrastructures: Capo Passero, Western Ionian Sea 3,600 meters of depth, and Catania Wester Ionian Sea 2,100 m depth. At the two sites, several research observatories have been run: OnDE, NEMO-SN1, SMO, KM3NeT-Italia most of them jointly operated between INFN and INGV. In all these observatories, passive acoustic sensors (hydrophones) have been installed. Passive Acoustics Monitoring (PAM) is nowadays the main tool of the bioacoustics to study marine mammals. In particular, receiving the sounds emitted by cetaceans from a multi-hydrophones array installed in a cabled seafloor observatory, a research about the ecological dynamics of the species may be performed. Data acquired with the hydrophones installed aboard the OnDE, SMO and KM3NeT-Italia observatories will be reported. Thanks to acquired data, the acoustic presence of the sperm whales was assessed and studied for several years (2005:2013). An "ad hoc" algorithm was also developed to allow the automatic identification of the "clicks" emitted by the sperm whales and measure the size of detected animals. According to the results obtained, the sperm whale population in the area is well-distributed in size, sex and sexual maturity. Although specimens more than 14 meters of length (old males) seem to be absent.

  11. Measurement of neutron yield by 62 MeV proton beam on a thick beryllium target

    NASA Astrophysics Data System (ADS)

    Osipenko, M.; Ripani, M.; Alba, R.; Ricco, G.; Schillaci, M.; Barbagallo, M.; Boccaccio, P.; Celentano, A.; Colonna, N.; Cosentino, L.; Del Zoppo, A.; Di Pietro, A.; Esposito, J.; Figuera, P.; Finocchiaro, P.; Kostyukov, A.; Maiolino, C.; Santonocito, D.; Scuderi, V.; Viberti, C. M.

    2013-09-01

    The design of a low-power prototype of neutron amplifier recently proposed within the INFN-E project indicated the need for more accurate data on the neutron yield produced by a proton beam with energy of about 70 MeV impinging on a thick beryllium target. Such measurement was performed at the LNS superconducting cyclotron, covering a wide angular range from 0° to 150° and a complete neutron energy interval from thermal to beam energy. Neutrons with energy above 0.5 MeV were measured by liquid scintillators exploiting their time of flight to determine the kinetic energy. For lower energy neutrons, down to thermal energy, a 3He detector was used. The obtained data are in good agreement with previous measurements at 0° using 66 MeV proton beam, covering neutron energies >10 MeV, as well as with measurements at few selected angles using protons of 46, 55 and 113 MeV energy. The present results extend the neutron yield data in the 60-70 MeV beam energy range. A comparison of measured yields to MCNP, FLUKA and Geant4 Monte Carlo simulations was performed.

  12. Ther FERMI FEL project at TRIESTE

    SciTech Connect

    Walker, R.P.; Bulfone, D.; Cargnello, F.

    1995-12-31

    The goal of the FERMI project - Free Electron Radiation and Matching Instrumentation - is to construct a new user facility for FEL radiation beams covering a broad spectral range (2-250 {mu}m) to complement the high brightness VUV/Soft-Xray radiation available from the ELETTRA synchrotron radiation facility at Trieste. A unique feature of the project will be the possibility of carrying out {open_quote}pump-probe{close_quote} experiments using synchronized radiation beams from FERMI and ELETTRA on the same sample. The project was launched at a meeting with Italian FEL experts held in Trieste on the 18th November 1994, chaired by C. Rubbia, as a collaboration between Sincrotrone Trieste, ENEA (Frascati), INFN (Frascati) and the University of Naples (Department of Electronic Engineering). The facility will make use of an existing linac, that forms part of the ELETTRA injection system, and a hall into which the beam can be extracted. In addition, for the first phase of the project equipment will be used from the suspended INFN/ENEA {open_quote}SURF{close_quote} FEL experiment, including the undulator, beam transport magnets and optical cavity. In this first International FEL Conference report on the project, we summarize the main features of the project, concentrating in particular on the most recent activities, including: results of measurements of the linac beam in the FEL mode of operation, further studies of the electron beam transport system including possibilities for bunch length manipulations, and further numerical calculations of the FEL performance.

  13. FOREWORD: TAUP 2005: Proceedings of the Ninth International Conference on Topics in Astroparticle and Underground Physics

    NASA Astrophysics Data System (ADS)

    Bottino, Alessandro; Coccia, Eugenio; Morales, Julio; Puimedónv, Jorge

    2006-04-01

    The ninth meeting of the TAUP Workshop Series, TAUP 2005, was organized by the University of Zaragoza and Laboratorio Subterráneo de Canfranc, jointly with the Laboratori Nazionali del Gran Sasso of the Italian Institute of Nuclear Physics (INFN). It was dedicated to the memory of professor Angel Morales, co-founder of the TAUP Series and a central figure in the scientific shaping and organization of the TAUP conferences since their inception in 1989. He and his group of collaborators laid, twenty years ago, the foundations of underground physics in Spain. To have TAUP 2005 hosted by the University of Zaragoza was a tangible way of honouring his memory. The Conference was concluded by a visit to the new installations of the Canfranc Laboratory, where a memorial ceremony was held in honour of Angel Morales, the driving force for the creation of that Laboratory. In TAUP 2005 all the various aspects of Astroparticle Physics have been covered, from Cosmology and Dark Constituents, to Gravitational Waves, to Neutrino Physics and Astrophysics, to High Energy Astrophysics, to Cosmic Rays and Gamma-Rays Astronomy. New and important scientific results were presented and debated in the plenary review talks and in a very large number of contributions in topical parallel sessions. As editors of these proceedings, we hope that this volume, which contains most of the talks and contributions presented at TAUP 2005, will provide a detailed state-of-the-art account of the various facets of Astroparticle Physics. We thank all the invited speakers and contributors who made this possible. Full coverage of the transparencies presented at the conference can be found on the website http://www.unizar.es/taup2005. At TAUP 2005 a memorial lecture was delivered by Art McDonald to commemorate John Bahcall, who passed away prematurely in August 2005. In this talk, his figure, as a pioneer and leader in the fields of Neutrino Physics, Astronomy and Astrophysics and as a man of great personal

  14. Measurement of neutron spectra generated by a 62 AMeV carbon-ion beam on a PMMA phantom using extended range Bonner sphere spectrometers

    NASA Astrophysics Data System (ADS)

    Bedogni, R.; Amgarou, K.; Domingo, C.; Russo, S.; Cirrone, G. A. P.; Pelliccioni, M.; Esposito, A.; Pola, A.; Introini, M. V.; Gentile, A.

    2012-07-01

    Neutrons constitute an important component of the radiation environment in hadron therapy accelerators. Their energy distribution may span from thermal up to hundred of MeV. The characterization of these fields in terms of dosimetric or spectrometric quantities is crucial for either the patient protection or the facility design aspects. To date, the Extended Range Bonner Sphere Spectrometer (ERBSS) is the only instrument able to simultaneously determine all spectral components in such workplaces. With the aim of providing useful data to the scientific community involved in neutron measurements at hadron therapy facilities, a measurement campaign was carried out at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA) of INFN-LNS (Laboratori Nazionali del Sud), where a 62 AMeV carbon ion is available. The beam was directed towards a PMMA phantom, simulating the patient, and two neutron measurement points were established at 0° and 90° with respect to the beam-line. The ERBSSs of UAB (Universidad Autónoma de Barcelona-Grup de Física de les Radiacions) and INFN (Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali di Frascati) were used to measure the resulting neutron fields. The two ERBSSs use different detectors and sphere diameters, and have been independently calibrated. The FRUIT code was used to unfold the results.

  15. Workplace testing of the new single sphere neutron spectrometer based on Dysprosium activation foils (Dy-SSS)

    NASA Astrophysics Data System (ADS)

    Bedogni, R.; Gómez-Ros, J. M.; Esposito, A.; Gentile, A.; Chiti, M.; Palacios-Pérez, L.; Angelone, M.; Tana, L.

    2012-08-01

    A photon insensitive passive neutron spectrometer consisting of a single moderating polyethylene sphere with Dysprosium activation foils arranged along three perpendicular axes was designed by CIEMAT and INFN. The device is called Dy-SSS (Dy foil-based Single Sphere Spectrometer). It shows nearly isotropic response in terms of neutron fluence up to 20 MeV. The first prototype, previously calibrated with 14 MeV neutrons, has been recently tested in workplaces having different energy and directional distributions. These are a 2.5 MeV nearly mono-chromatic and mono-directional beam available at the ENEA Frascati Neutron Generator (FNG) and the photo-neutron field produced in a 15 MV Varian CLINAC DHX medical accelerator, located in the Ospedale S. Chiara (Pisa). Both neutron spectra are known through measurements with a Bonner Sphere Spectrometer. In both cases the experimental response of the Dy-SSS agrees with the reference data. Moreover, it is demonstrated that the spectrometric capability of the new device are independent from the directional distribution of the neutron field. This opens the way to a new generation of moderation-based neutron instruments, presenting all advantages of the Bonner sphere spectrometer without the disadvantage of the repeated exposures. This concept is being developed within the NESCOFI@BTF project of INFN (Commissione Scientifica Nazionale 5).

  16. The computing and data infrastructure to interconnect EEE stations

    NASA Astrophysics Data System (ADS)

    Noferini, F.

    2016-07-01

    The Extreme Energy Event (EEE) experiment is devoted to the search of high energy cosmic rays through a network of telescopes installed in about 50 high schools distributed throughout the Italian territory. This project requires a peculiar data management infrastructure to collect data registered in stations very far from each other and to allow a coordinated analysis. Such an infrastructure is realized at INFN-CNAF, which operates a Cloud facility based on the OpenStack opensource Cloud framework and provides Infrastructure as a Service (IaaS) for its users. In 2014 EEE started to use it for collecting, monitoring and reconstructing the data acquired in all the EEE stations. For the synchronization between the stations and the INFN-CNAF infrastructure we used BitTorrent Sync, a free peer-to-peer software designed to optimize data syncronization between distributed nodes. All data folders are syncronized with the central repository in real time to allow an immediate reconstruction of the data and their publication in a monitoring webpage. We present the architecture and the functionalities of this data management system that provides a flexible environment for the specific needs of the EEE project.

  17. Performance of upstream interaction region detectors for the FIRST experiment at GSI

    NASA Astrophysics Data System (ADS)

    Abou-Haidar, Z.; Agodi, C.; Alvarez, M. A. G.; Anelli, M.; Aumann, T.; Battistoni, G.; Bocci, A.; Böhlen, T. T.; Boudard, A.; Brunetti, A.; Carpinelli, M.; Cirrone, G. A. P.; Cortes-Giraldo, M. A.; Cuttone, G.; De Napoli, M.; Durante, M.; Fernández-García, J. P.; Finck, C.; Gallardo, M. I.; Golosio, B.; Iarocci, E.; Iazzi, F.; Ickert, G.; Introzzi, R.; Juliani, D.; Krimmer, J.; Kurz, N.; Labalme, M.; Leifels, Y.; Le F{èvre, A.; Leray, S.; Marchetto, F.; Monaco, V.; Morone, M. C.; Oliva, P.; Paoloni, A.; Patera, V.; Piersanti, L.; Pleskac, R.; Quesada, J. M.; Randazzo, N.; Romano, F.; Rossi, D.; Rosso, V.; Rousseau, M.; Sacchi, R.; Sala, P.; Sarti, A.; Schuy, C.; Sciubba, A.; Sfienti, C.; Simon, H.; Sipala, V.; Spiriti, E.; Stuttge, L.; Tropea, S.; Younis, H.

    2012-02-01

    The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI has been designed to study carbon fragmentation, measuring 12C double differential cross sections (∂2σ/∂θ∂E) for different beam energies between 100 and 1000 MeV/u. The experimental setup integrates newly designed detectors in the, so called, Interaction Region around the graphite target. The Interaction Region upstream detectors are a 250 μm thick scintillator and a drift chamber optimized for a precise measurement of the ions interaction time and position on the target. In this article we review the design of the upstream detectors along with the preliminary results of the data taking performed on August 2011 with 400 MeV/u fully stripped carbon ion beam at GSI. Detectors performances will be reviewed and compared to those obtained during preliminary tests, performed with 500 MeV electrons (at the BTF facility in the INFN Frascati Laboratories) and 80 MeV/u protons and carbon ions (at the INFN LNS Laboratories in Catania).

  18. The Experimental Discovery of Double-Charm Baryons

    NASA Astrophysics Data System (ADS)

    Engelfried, Jürgen; Selex Collaboration

    2005-04-01

    In 2002, the SELEX [The SELEX (Fermilab E781) Collaboration: Ball State University, Bogazici University, Carnegie-Mellon University, Centro Brasileiro de Pesquisas Fisicas, Fermilab, Institute For High Energy Physics (Protvino), Institute of High Energy Physics (Beijing), Institute of Theoretical and Experimental Physics (Moscow), Max-Planck-Institute for Nuclear Physics, Moscow State University, Petersburg Nuclear Physics Institute, Tel Aviv University, Universidad Autónoma de San Luis Potosí, Universidade Federal da Paraíba, H. H. Wills Physics Laboratory, University of Bristol, University of Iowa, University of Michigan-Flint, University of Rochester, University of Rome La Sapienza and INFN, University of São Paulo, University of Trieste and INFN. http://www-selex.fnal.gov] Experiment (Fermilab E781) reported the first observation of a member of the family of doubly charmed baryons [SELEX Collaboration, M. Mattson et al.: First observation of the doubly charmed baryonΞcc+. Phys. Rev. Letters 89 (2002) 112001, [ arXiv:hep-ex/0208014

  19. PREFACE: International Conference on Topics in Astroparticle and Underground Physics (TAUP 2011)

    NASA Astrophysics Data System (ADS)

    Oberauer, Lothar; Raffelt, Georg; Wagner, Robert

    2012-07-01

    The 12th edition of the International Conference on Topics in Astroparticle and Underground Physics (TAUP 2011) was held 5-9 September 2011 in Munich (and for the first time in Germany). It was organized by the Max Planck Institute for Physics (MPP), the Technical University Munich (TUM) and the Cluster of Excellence 'Origin and Structure of the Universe'. The conference was held in the 'Künstlerhaus', a traditional downtown location for artistic festivities. The meeting attracted 317 participants (61 of which were women) from 29 countries, see figure below. The topics covered by the meeting were Cosmology and particle physics, Dark matter and its detection, Neutrino physics and astrophysics, Gravitational waves and High-energy astrophysics and cosmic rays, and the various interfaces between these areas. The scientific sessions consisted of five mornings of plenary talks, four afternoons of parallel sessions, and an evening poster session. The co-founder of the conference series, Alessandro Bottino, has decided to retire from the position of chairman of the TAUP Steering Committee after the completion of TAUP 2011. On behalf of all followers of this series, we thank him for having started these inspiring events and his many years of dedicated service. We thank all speakers, conveners and participants as well as the members of the organizing, steering and international advisory committee for making this a successful and memorable meeting. Lothar Oberauer, Georg Raffelt, Robert Wagner Proceedings editors Figure Committees International Advisory Committee G AntonUniversity of Erlangen E AprileColumbia University M Baldo-CeolinUniversity of Padova R BattistonUniversity of Perugia & INFN L BergströmUniversity Stockholm R BernabeiUniversity of Rome 'Tor Vergata' A BettiniLSC Canfranc P BinetruyAPC Paris J BlümerKarlsruhe Institute of Technology B CabreraStanford University A CaldwellMax Planck Institute for Physics M ChenQueens University E CocciaUniversity of Rome

  20. MoonLIGHT: A USA-Italy lunar laser ranging retroreflector array for the 21st century

    NASA Astrophysics Data System (ADS)

    Martini, M.; Dell'Agnello, S.; Currie, D.; Delle Monache, G.; Vittori, R.; Chandler, J. F.; Cantone, C.; Boni, A.; Berardi, S.; Patrizi, G.; Maiello, M.; Garattini, M.; Lops, C.; March, R.; Bellettini, G.; Tauraso, R.; Intaglietta, N.; Tibuzzi, M.; Murphy, T. W.; Bianco, G.; Ciocci, E.

    2012-12-01

    Since the 1970s Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflector (CCR) arrays (developed by the University of Maryland, UMD) have supplied significant tests of General Relativity: possible changes in the gravitational constant, gravitational self-energy, weak equivalence principle, geodetic precession, inverse-square force-law. LLR has also provided significant information on the composition and origin of the Moon. This is the only Apollo experiment still in operation. In the 1970s Apollo LLR arrays contributed a negligible fraction of the ranging error budget. Since the ranging capabilities of ground stations improved by more than two orders of magnitude, now, because of the lunar librations, Apollo CCR arrays dominate the error budget. With the project MoonLIGHT (Moon Laser Instrumentation for General relativity High-accuracy Tests), in 2006 INFN-LNF joined UMD in the development and test of a new-generation LLR payload made by a single, large CCR (100 mm diameter) unaffected by librations. In particular, INFN-LNF built and is operating a new experimental apparatus (Satellite/lunar laser ranging Characterization Facility, SCF) and created a new industry-standard test procedure (SCF-Test) to characterize and model the detailed thermal behavior and the optical performance of CCRs in laboratory-simulated space conditions, for industrial and scientific applications. Our key experimental innovation is the concurrent measurement and modeling of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of retroreflector payloads under thermal conditions produced with a solar simulator. The apparatus includes infrared cameras for non-invasive thermometry, thermal control and real-time payload movement to simulate satellite orientation on orbit with respect to solar illumination and laser interrogation beams. These capabilities provide: unique pre-launch performance validation of the space segment of LLR/SLR (Satellite Laser

  1. Extreme QCD 2012 (xQCD)

    NASA Astrophysics Data System (ADS)

    2013-04-01

    Acknowledgements This conference would not have been possible without the generous support from Brookhaven National Laboratory and the George Washington University INS and IMPACT institutes, Columbian College of Arts and Sciences, the Office of Vice-President for Research, and the Department of Physics. We thank them wholeheartedly. We are also very grateful for the support of our colleagues on the local organizing committee, Walter Freeman and Frank Lee, and on the International Advisory Committee: Simon Hands, Tetsuo Hatsuda, Frithjof Karsch, Maria Paola Lombardo, Tereza Mendes, Atsushi Nakamura, Owe Philipsen, Claudia Ratti, Paul Romatschke, Misha Stephanov, and Nu Xu. List of participants Alexandru, Andrei George Washington University Bazavov, Alexei Brookhaven National Laboratory Bloch, Jacques University of Regensburg Braun-Munzinger, Peter EMMI, GSI Breto Rangel, Guillermo CMS/UC Davis D'Elia, Massimo University of Pisa, INFN Dexheimer, Veronica UFSC - Federal University of Santa Catarina Ding, Heng-Tong Brookhaven National Laboratory Dion, Alan Stony Brook University Dumitru, Adrian RBRC and Baruch College, CUNY Freeman, Walter George Washington University Gavai, Rajiv Tata Institute (TIFR), Mumbai Hanada, Masanori KEK Theory Center Hands, Simon Swansea University Hegde, Prasad Brookhaven National Laboratory Heinke, Craig University of Alberta Horvath, Ivan University of Kentucky Karsch, Frithjof Brookhaven National Laboratory Krieg, Stefan Wuppertal University Lattimer, James Stony Brook University Lee, Frank George Washington University Li, Anyi Institute for Nuclear Theory Liu, Keh-Fei University of Kentucky Lombardo, Maria Paola INFN - LNF Lottini, Stefano Goethe University, Frankfurt am Main Maezawa, Yu Brookhaven National Laboratory Miura, Kohtaroh Laboratori Nazionali di Frascati - INFN Monnai, Akihiko The University of Tokyo Mukherjee, Swagato Brookhaven National Laboratory Myers, Joyce University of Groningen Nakamura, Atsushi RIISE, Hiroshima

  2. RELAP5-3D thermal hydraulic analysis of the target cooling system in the SPES experimental facility

    NASA Astrophysics Data System (ADS)

    Giardina, M.; Castiglia, F.; Buffa, P.; Palermo, G.; Prete, G.

    2014-11-01

    The SPES (Selective Production of Exotic Species) experimental facility, under construction at the Italian National Institute of Nuclear Physics (INFN) Laboratories of Legnaro, Italy, is a second generation Isotope Separation On Line (ISOL) plant for advanced nuclear physic studies. The UCx target-ion source system works at temperature of about 2273 K, producing a high level of radiation (105 Sv/h), for this reason a careful risk analysis for the target chamber is among the major safety issues. In this paper, the obtained results of thermofluid-dynamics simulations of accidental transients in the SPES target cooling system are reported. The analysis, performed by using the RELAP5-3D 2.4.2 qualified thermal-hydraulic system code, proves good safety performance of this system during different accidental conditions.

  3. The SPES Project at LNL

    SciTech Connect

    Andrighetto, A.; Carturan, S.; Gramegna, F.; Prete, G.; Biasetto, L.; Manzolaro, M.; Benetti, P.; Colombo, P.; Meneghetti, G.; Monelli, B.; Zanonato, P.

    2009-03-10

    The main goal of the SPES project at Laboratori Nazionali di Legnaro of INFN (Italy) is to provide an accelerator system to perform forefront research in nuclear physics by studying nuclei far from stability. The SPES project is based on the production of neutron-rich radioactive nuclei in the mass range 80 to 160, by the fission of uranium at the rate of 10{sup 13} fission/s. The Radioactive Ion Beam (RIB) will be produced by the Isotope Separator On Line (ISOL) technique using the proton-induced fission in a uranium carbide target. The energy of the radioactive beams on target will range from a few MeV/u up to 10 MeV/u for A = 130 using the existing ALPI linac as the post-accelerator.

  4. Research and development on materials for the SPES target

    NASA Astrophysics Data System (ADS)

    Corradetti, Stefano; Andrighetto, Alberto; Manzolaro, Mattia; Scarpa, Daniele; Vasquez, Jesus; Rossignoli, Massimo; Monetti, Alberto; Calderolla, Michele; Prete, Gianfranco

    2014-03-01

    The SPES project at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro) is focused on the production of radioactive ion beams. The core of the SPES facility is constituted by the target, which will be irradiated with a 40 MeV, 200 µA proton beam in order to produce radioactive species. In order to efficiently produce and release isotopes, the material constituting the target should be able to work under extreme conditions (high vacuum and temperatures up to 2000 °C). Both neutron-rich and proton-rich isotopes will be produced; in the first case, carbon dispersed uranium carbide (UCx) will be used as a target, whereas to produce p-rich isotopes, several types of targets will have to be irradiated. The synthesis and characterization of different types of material will be reported. Moreover, the results of irradiation and isotopes release tests on different uranium carbide target prototypes will be discussed.

  5. PREFACE: Young Researcher Meeting, Trieste 2013

    NASA Astrophysics Data System (ADS)

    Agostini, F.; Antolini, C.; Aversa, R.; Cattani, G.; Martinelli, M.; Mazzaferro, L.; Migliaccio, M.; Paci, F.; Pietrobon, D.; Ricci Pacifici, D.; Stellato, F.; Veneziani, M.

    2013-12-01

    YRM logo The Young Researcher Meeting (www.yrmr.it) has been a rapidly growing event for the last few years. Together with other initiatives which have emerged in several research areas, the young researcher meeting marks the awareness and the desire of PhD students, postdoctoral fellows and young researchers to play a major role in scientific progress. Devoted to the discussion and the interchange of new developments and ideas in physics, the meeting is primarily aimed at graduate students and postdoctoral researchers, who are encouraged to present their work in an informal atmosphere. One of the main purposes of the conference is to create an international network of young researchers, both experimentalists and theorists, and fruitful collaborations across the different branches of physics. Born in Rome in 2009, after three editions that strengthened it, the Young Researcher Meeting 2013 was held in Trieste. Propelled by the past success, the fourth meeting was a two-day conference on 3-4June. It was sponsored by the International School for Advanced Studies - SISSA - and the University of Padova, thus acquiring an even further international drive. In this volume, we collect some of the contributions that were presented at the conference. They cover topics in astrophysics and cosmology, particle and theoretical physics, soft and condensed matter, biophysics and medical physics. YRM Organising and Editorial Committee Fabio Agostini (fabio.agostini@roma2.infn.it) Dipartimento di Fisica, Università di Roma 'Tor Vergata' Via della Ricerca Scientifica 1, 00133 Roma, Italy Claudia Antolini (claudia.antolini@sissa.it) SISSA - Scuola Internazionale Superiore di Studi Avanzati Via Bonomea 265, 34136 Trieste, Italy Rossella Aversa (raversa@sissa.it) SISSA - Scuola Internazionale Superiore di Studi Avanzati Via Bonomea 265, 34136 Trieste, Italy Giordano Cattani (giordano.cattani@gmail.com) Matteo Martinelli (mmartin@sissa.it) SISSA - Scuola Internazionale Superiore di

  6. Ionization efficiency estimations for the SPES surface ion source

    NASA Astrophysics Data System (ADS)

    Manzolaro, M.; Andrighetto, A.; Meneghetti, G.; Rossignoli, M.; Corradetti, S.; Biasetto, L.; Scarpa, D.; Monetti, A.; Carturan, S.; Maggioni, G.

    2013-12-01

    Ion sources play a crucial role in ISOL (Isotope Separation On Line) facilities determining, with the target production system, the ion beam types available for experiments. In the framework of the SPES (Selective Production of Exotic Species) INFN (Istituto Nazionale di Fisica Nucleare) project, a preliminary study of the alkali metal isotopes ionization process was performed, by means of a surface ion source prototype. In particular, taking into consideration the specific SPES in-target isotope production, Cs and Rb ion beams were produced, using a dedicated test bench at LNL (Laboratori Nazionali di Legnaro). In this work the ionization efficiency test results for the SPES Ta surface ion source prototype are presented and discussed.

  7. A new H2+ source: Conceptual study and experimental test of an upgraded version of the VIS—Versatile ion source

    NASA Astrophysics Data System (ADS)

    Castro, G.; Torrisi, G.; Celona, L.; Mascali, D.; Neri, L.; Sorbello, G.; Leonardi, O.; Patti, G.; Castorina, G.; Gammino, S.

    2016-08-01

    The versatile ion source is an off-resonance microwave discharge ion source which produces a slightly overdense plasma at 2.45 GHz of pumping wave frequency extracting more than 60 mA proton beams and 50 mA He+ beams. DAEδALUS and IsoDAR experiments require high intensities for H2+ beams to be accelerated by high power cyclotrons for neutrinos generation. In order to fulfill the new requirements, a new plasma chamber and injection system has been designed and manufactured for increasing the H2+ beam intensity. In this paper the studies for the increasing of the H2+/p ratio and for the design of the new plasma chamber and injection system will be shown and discussed together with the experimental tests carried out at Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) and at Best Cyclotron Systems test-bench in Vancouver, Canada.

  8. Noise reduction in muon tomography for detecting high density objects

    NASA Astrophysics Data System (ADS)

    Benettoni, M.; Bettella, G.; Bonomi, G.; Calvagno, G.; Calvini, P.; Checchia, P.; Cortelazzo, G.; Cossutta, L.; Donzella, A.; Furlan, M.; Gonella, F.; Pegoraro, M.; Rigoni Garola, A.; Ronchese, P.; Squarcia, S.; Subieta, M.; Vanini, S.; Viesti, G.; Zanuttigh, P.; Zenoni, A.; Zumerle, G.

    2013-12-01

    The muon tomography technique, based on multiple Coulomb scattering of cosmic ray muons, has been proposed as a tool to detect the presence of high density objects inside closed volumes. In this paper a new and innovative method is presented to handle the density fluctuations (noise) of reconstructed images, a well known problem of this technique. The effectiveness of our method is evaluated using experimental data obtained with a muon tomography prototype located at the Legnaro National Laboratories (LNL) of the Istituto Nazionale di Fisica Nucleare (INFN). The results reported in this paper, obtained with real cosmic ray data, show that with appropriate image filtering and muon momentum classification, the muon tomography technique can detect high density materials, such as lead, albeit surrounded by light or medium density material, in short times. A comparison with algorithms published in literature is also presented.

  9. Development of a scintillation-fiber detector for real-time particle tracking

    NASA Astrophysics Data System (ADS)

    Lo Presti, D.; Bonanno, D. L.; Longhitano, F.; Pugliatti, C.; Russo, G. V.; Aiello, S.; Cirrone, G. A. P.; Giordano, V.; Leonora, E.; Randazzo, N.; Romano, F.; Russo, M.; Sipala, V.; Stancampiano, C.; Reito, S.

    2013-04-01

    The prototype of the OFFSET (Optical Fiber Folded Scintillating Extended Tracker) tracker is presented. It exploits a novel system for particle tracking, designed to achieve real-time imaging, large detection areas, and a high spatial resolution especially suitable for use in medical diagnostics. The main results regarding the system architecture have been used as a demonstration of the technique which has been patented by the Istituto Nazionale di Fisica Nucleare (INFN). The prototype of this tracker, presented in this paper, has a 20 × 20 cm2 sensitive area, consisting of two crossed ribbons of 500 micron square scintillating fibers. The track position information is extracted in real time in an innovative way, using a reduced number of read-out channels to obtain very large detection area with moderate enough costs and complexity. The performance of the tracker was investigated using beta sources, cosmic rays, and a 62 MeV proton beam.

  10. Microwave frequency sweep interferometer for plasma density measurements in ECR ion sources: Design and preliminary results

    NASA Astrophysics Data System (ADS)

    Torrisi, Giuseppe; Mascali, David; Neri, Lorenzo; Leonardi, Ornella; Sorbello, Gino; Celona, Luigi; Castro, Giuseppe; Agnello, Riccardo; Caruso, Antonio; Passarello, Santi; Longhitano, Alberto; Isernia, Tommaso; Gammino, Santo

    2016-02-01

    The Electron Cyclotron Resonance Ion Sources (ECRISs) development is strictly related to the availability of new diagnostic tools, as the existing ones are not adequate to such compact machines and to their plasma characteristics. Microwave interferometry is a non-invasive method for plasma diagnostics and represents the best candidate for plasma density measurement in hostile environment. Interferometry in ECRISs is a challenging task mainly due to their compact size. The typical density of ECR plasmas is in the range 1011-1013 cm-3 and it needs a probing beam wavelength of the order of few centimetres, comparable to the chamber radius. The paper describes the design of a microwave interferometer developed at the LNS-INFN laboratories based on the so-called "frequency sweep" method to filter out the multipath contribution in the detected signals. The measurement technique and the preliminary results (calibration) obtained during the experimental tests will be presented.

  11. Microwave frequency sweep interferometer for plasma density measurements in ECR ion sources: Design and preliminary results.

    PubMed

    Torrisi, Giuseppe; Mascali, David; Neri, Lorenzo; Leonardi, Ornella; Sorbello, Gino; Celona, Luigi; Castro, Giuseppe; Agnello, Riccardo; Caruso, Antonio; Passarello, Santi; Longhitano, Alberto; Isernia, Tommaso; Gammino, Santo

    2016-02-01

    The Electron Cyclotron Resonance Ion Sources (ECRISs) development is strictly related to the availability of new diagnostic tools, as the existing ones are not adequate to such compact machines and to their plasma characteristics. Microwave interferometry is a non-invasive method for plasma diagnostics and represents the best candidate for plasma density measurement in hostile environment. Interferometry in ECRISs is a challenging task mainly due to their compact size. The typical density of ECR plasmas is in the range 10(11)-10(13) cm(-3) and it needs a probing beam wavelength of the order of few centimetres, comparable to the chamber radius. The paper describes the design of a microwave interferometer developed at the LNS-INFN laboratories based on the so-called "frequency sweep" method to filter out the multipath contribution in the detected signals. The measurement technique and the preliminary results (calibration) obtained during the experimental tests will be presented.

  12. Femtosecond timing-jitter between photo-cathode laser and ultra-short electron bunches by means of hybrid compression

    NASA Astrophysics Data System (ADS)

    Pompili, R.; Anania, M. P.; Bellaveglia, M.; Biagioni, A.; Castorina, G.; Chiadroni, E.; Cianchi, A.; Croia, M.; Di Giovenale, D.; Ferrario, M.; Filippi, F.; Gallo, A.; Gatti, G.; Giorgianni, F.; Giribono, A.; Li, W.; Lupi, S.; Mostacci, A.; Petrarca, M.; Piersanti, L.; Di Pirro, G.; Romeo, S.; Scifo, J.; Shpakov, V.; Vaccarezza, C.; Villa, F.

    2016-08-01

    The generation of ultra-short electron bunches with ultra-low timing-jitter relative to the photo-cathode (PC) laser has been experimentally proved for the first time at the SPARC_LAB test-facility (INFN-LNF, Frascati) exploiting a two-stage hybrid compression scheme. The first stage employs RF-based compression (velocity-bunching), which shortens the bunch and imprints an energy chirp on it. The second stage is performed in a non-isochronous dogleg line, where the compression is completed resulting in a final bunch duration below 90 fs (rms). At the same time, the beam arrival timing-jitter with respect to the PC laser has been measured to be lower than 20 fs (rms). The reported results have been validated with numerical simulations.

  13. The EUAsiaGrid Project

    NASA Astrophysics Data System (ADS)

    Paganoni, Marco

    The EUAsiaGrid proposal contributes to the aims of the Research Infrastructures part of the EU Seventh Framework Programme (FP7) by promoting interoperation between the European and the Asian-Pacific Grids. The project, with a total number of 15 partners coordinated by INFN, started on April 1st 2008. It will disseminate the knowledge about the EGEE Grid infrastructure, organize specific training events and support applications both within the scientific communities with an already long experience in the Computing Grids (High Energy Physics, Computational Chemistry, Bioinformatics and Biomedics) and in the most recent ones (Social Sciences, Disaster Mitigation, Cultural Heritage). Ultimately the EUAsiaGrid project will pave the way towards a common e-Infrastructure with the European and the Asian Grids.

  14. Note: Enhanced production of He+ from the Versatile Ion Source (VIS) in off-resonance configuration

    NASA Astrophysics Data System (ADS)

    Castro, G.; Mascali, D.; Celona, L.; Gammino, S.; Caliri, C.; Bartolo, F. Di; Lanaia, D.; Mazzaglia, M.; Miracoli, R.; Neri, L.; Torrisi, G.; Altana, C.; Ciavola, G.

    2014-09-01

    The Versatile Ion Source (VIS) is a microwave discharge ion source installed at INFN-LNS and here used as test-bench for the production of high intensity low emittance proton beams and for studies on plasma physics. A series of measurements have been carried out with VIS in order to test the source with light ions. In particular a He+ beam has been characterized in terms of plasma discharge parameters. The experiment has been triggered by the observation of X-radiation emission from the plasma for some configuration of the magnetic field profile. The plasma electron energy distribution function is in fact modified when in some regions of the plasma chamber under-resonance discharge takes place, fulfilling the condition that allows the electromagnetic wave to electrostatic wave conversion. These tests allowed obtaining more than 50 mA of He+ beams.

  15. Background modeling for the GERDA experiment

    SciTech Connect

    Becerici-Schmidt, N.; Collaboration: GERDA Collaboration

    2013-08-08

    The neutrinoless double beta (0νββ) decay experiment GERDA at the LNGS of INFN has started physics data taking in November 2011. This paper presents an analysis aimed at understanding and modeling the observed background energy spectrum, which plays an essential role in searches for a rare signal like 0νββ decay. A very promising preliminary model has been obtained, with the systematic uncertainties still under study. Important information can be deduced from the model such as the expected background and its decomposition in the signal region. According to the model the main background contributions around Q{sub ββ} come from {sup 214}Bi, {sup 228}Th, {sup 42}K, {sup 60}Co and α emitting isotopes in the {sup 226}Ra decay chain, with a fraction depending on the assumed source positions.

  16. EEE - Extreme Energy Events: an astroparticle physics experiment in Italian High Schools

    NASA Astrophysics Data System (ADS)

    Abbrescia, M.; Avanzini, C.; Baldini, L.; Baldini Ferroli, R.; Batignani, G.; Bencivenni, G.; Bossini, E.; Bressan, E.; Chiavassa, A.; Cicalò, C.; Cifarelli, L.; Coccia, E.; Corvaglia, A.; De Gruttola, D.; De Pasquale, S.; Di Giovanni, A.; D'Incecco, M.; Dreucci, M.; Fabbri, F. L.; Fattibene, E.; Ferrarov, A.; Forster, R.; Frolov, V.; Galeotti, P.; Garbini, M.; Gemme, G.; Gnesi, I.; Grazzi, S.; Gustavino, C.; Hatzifotiadou, D.; La Rocca, P.; Maggiora, A.; Maron, G.; Mazziotta, M. N.; Miozzi, S.; Noferini, F.; Nozzoli, F.; Panareo, M.; Panetta, M. P.; Paoletti, R.; Perasso, L.; Pilo, F.; Piragino, G.; Riggi, F.; Righini, G. C.; Rodriguez Rodriguez, A.; Sartorelli, G.; Scapparone, E.; Schioppa, M.; Scribano, A.; Selvi, M.; Serci, S.; Siddi, E.; Squarcia, S.; Taiuti, M.; Terreni, G.; Vistoli, M. C.; Votano, L.; Williams, M. C. S.; Zani, S.; Zichichi, A.; Zuyeuski, R.

    2016-05-01

    The Extreme Energy Events project (EEE) is aimed to study Extensive Air Showers (EAS) from primary cosmic rays of more than 1018 eV energy detecting the ground secondary muon component using an array of telescopes with high spatial and time resolution. The second goal of the EEE project is to involve High School teachers and students in this advanced research work and to initiate them in scientific culture: to reach both purposes the telescopes are located inside High School buildings and the detector construction, assembling and monitoring - together with data taking and analysis - are done by researchers from scientific institutions in close collaboration with them. At present there are 42 telescopes in just as many High Schools scattered all over Italy, islands included, plus two at CERN and three in INFN units. We report here some preliminary physics results from the first two common data taking periods together with the outreach impact of the project.

  17. Single-crystal Diamond Detector for DT and DD plasmas diagnostic

    NASA Astrophysics Data System (ADS)

    Rebai, M.; Cazzaniga, C.; Tardocchi, M.; Grosso, G.; Croci, G.; Perelli Cippo, E.; Calvani, P.; Girolami, M.; Trucchi, D. M.; Gorini, G.

    2016-11-01

    Single-crystal Diamond Detectors (SDD) are good candidates as high-energy neutron detectors in the extreme conditions of the next generation thermonuclear fusion facilities like the ITER experiment, due to their high radiation hardness, fast response time and small size. Neutron detection in SDDs is based on the collection of electron-hole pairs produced by charged particles generated by neutron interaction on 12 C . In this work the SDD response to neutrons with energies between 2.8 and 3.8MeV was determined at the Legnaro CN accelerator at the INFN Laboratories in Legnaro (PD, Italy). This work is relevant for the characterization of SDDs response functions, which are key points for Deuterium-Deuterium and Deuterium-Tritium plasma diagnostic.

  18. Study of cluster structures in 10Be and 16C neutron-rich nuclei via break-up reactions

    NASA Astrophysics Data System (ADS)

    Dell'Aquila, D.; Acosta, L.; Amorini, F.; Andolina, R.; Auditore, L.; Berceanu, I.; Cardella, G.; Chatterjiee, M. B.; De Filippo, E.; Francalanza, L.; Gnoffo, B.; Grzeszczuk, A.; Lanzalone, G.; Lombardo, I.; Martorana, N.; Minniti, T.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Pop, A.; Porto, F.; Quattrocchi, L.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Vigilante, M.

    2016-05-01

    Projectile break-up reactions induced on polyethylene (CH2) target are used in order to study the spectroscopy of 10Be and 16C nuclei. For the present experiment we used 10Be and 16C beams delivered by the FRIBs facility at INFN-LNS, and the CHIMERA 4π multi-detector. 10Be and 16C structures are studied via a relative energy analysis of break-up fragments. The 4He+6He break-up channel allowed us to study the spectroscopy of 10Be; in particular we find evidence of a new state in 10Be at 13.5 MeV excitation energy. The 16C nucleus is studied via 6He-10Be correlation; we find the fingerprint of a possible state at about 20.6 MeV

  19. BaBar superconducting coil: design, construction and test

    SciTech Connect

    Bell, R A; Berndt, M; Burgess, W; Craddock, W; Dormicchi, O; Fabbricatore, P; Farinon, S; Keller, L; Moreschi, P; Musenich, R; O'Connor, T G; Penco, R; Priano, C; Shen, S; Valente, P

    2001-01-26

    The BABAR Detector, located in the PEP-II B-Factory at the Stanford Linear Accelerator Center, includes a large 1.5 Tesla superconducting solenoid, 2.8 m bore and length 3.7 m. The two layer solenoid is wound with an aluminum stabilized conductor which is graded axially to produce a {+-} 3% field uniformity in the tracking region. This paper summarizes the 3 year design, fabrication and testing program of the superconducting solenoid. The work was carried out by an international collaboration between INFN, LLNL and SLAC. The coil was constructed by Ansaldo Energia. Critical current measurements of the superconducting strand, cable and conductor, cool-down, operation with the thermo-siphon cooling, fast and slow discharges, and magnetic forces are discussed in detail.

  20. Clustering microcalcifications techniques in digital mammograms

    NASA Astrophysics Data System (ADS)

    Díaz, Claudia. C.; Bosco, Paolo; Cerello, Piergiorgio

    2008-11-01

    Breast cancer has become a serious public health problem around the world. However, this pathology can be treated if it is detected in early stages. This task is achieved by a radiologist, who should read a large amount of mammograms per day, either for a screening or diagnostic purpose in mammography. However human factors could affect the diagnosis. Computer Aided Detection is an automatic system, which can help to specialists in the detection of possible signs of malignancy in mammograms. Microcalcifications play an important role in early detection, so we focused on their study. The two mammographic features that indicate the microcalcifications could be probably malignant are small size and clustered distribution. We worked with density techniques for automatic clustering, and we applied them on a mammography CAD prototype developed at INFN-Turin, Italy. An improvement of performance is achieved analyzing images from a Perugia-Assisi Hospital, in Italy.

  1. SPECIAL SEMINAR - The NOTTE experiment, or how to become a Total Solar Eclipse chaser

    ScienceCinema

    None

    2016-07-12

    The NOTTE experiment (Neutrino Oscillations with Telescope during Total Eclipse) aims at searching for visible photons emitted through a possible radiative decay of solar neutrinos. The experiment and the expeditions organized by a group of physicists and astrophysicists from INFN and INAF Bologna hunting for Total Solar Eclipses from 1998 to 2006 wil be described. The results of observations performed during total solar eclipse expeditions in 2001 (Zambia) and 2006 (Sahara desert, Libya) are presented and a beautiful photo gallery will be shown. Other peculiar observations that can be made during a solar eclipse are also illustrated. The seminar will be followed by a brief presentation of future camps for solar eclipse chasers and scientists organized in 2008 in Russia, Kazakhstan, China and Mongolia, in 2009 in Shanghai and on the Easter Island in 2010.

  2. A new H2 (+) source: Conceptual study and experimental test of an upgraded version of the VIS-Versatile ion source.

    PubMed

    Castro, G; Torrisi, G; Celona, L; Mascali, D; Neri, L; Sorbello, G; Leonardi, O; Patti, G; Castorina, G; Gammino, S

    2016-08-01

    The versatile ion source is an off-resonance microwave discharge ion source which produces a slightly overdense plasma at 2.45 GHz of pumping wave frequency extracting more than 60 mA proton beams and 50 mA He(+) beams. DAEδALUS and IsoDAR experiments require high intensities for H2 (+) beams to be accelerated by high power cyclotrons for neutrinos generation. In order to fulfill the new requirements, a new plasma chamber and injection system has been designed and manufactured for increasing the H2 (+) beam intensity. In this paper the studies for the increasing of the H2 (+)/p ratio and for the design of the new plasma chamber and injection system will be shown and discussed together with the experimental tests carried out at Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) and at Best Cyclotron Systems test-bench in Vancouver, Canada. PMID:27587109

  3. Design and testing of the 1.5 T superconducting solenoid for the BABAR detector at PEP-II in SLAC

    SciTech Connect

    O'Connor, T G; Shen, S; Fabbricatore, P; Farinon, S; Musenich, R; Priano, C; Bell, R A; Brendt, M; Burgess, W; Craddock, W; Keller, L; Dormicchi, O; Moreschi, P; Penco, R; Valente, P; Valle, N

    2001-01-26

    The 1.5 Tesla superconducting solenoid is part of the BABAR Detector located in the PEP-II B-Factory machine at the Stanford Linear Accelerator Center. The solenoid has a 2.8 m bore and is 3.7 m long. The two layer solenoid is wound with an aluminum stabilized conductor which is graded axially to produce a {+-} 3% field uniformity in the tracking region. The 24 month fabrication, 3 month installation and 1 month commissioning of the solenoid were completed on time and budget. This paper summarizes the culmination of a 3 year design, fabrication and testing program of the BABAR superconducting solenoid. The work was completed by an international collaboration between Ansaldo, INFN, LLNL, and SLAC. Critical current measurements of the superconducting strand, cable and conductor, cool-down, operation with the thermo-siphon cooling, fast and slow discharges, and magnetic forces are discussed in detail.

  4. Photon Identification with Segmented Germanium Detectors in Low Radiation Environments

    SciTech Connect

    Abt, I.; Caldwell, A.; Kroeninger, K.; Liu, J.; Liu, X.; Majorovits, B.; Stelzer, F.

    2007-03-28

    Effective identification of photon-induced events is essential for a new generation of double beta-decay experiments. One such experiment is the GERmanium Detector Array, GERDA, located at the INFN Gran Sasso National Laboratory (LNGS) in Italy. It uses germanium, enriched in 76Ge, as source and detector, and aims at a background level of less than 10-3 counts/(kg {center_dot} keV {center_dot} y) in the region of the Q{beta}{beta}-value. Highly segmented detectors are being developed for this experiment. A detailed GEANT4 Monte Carlo study about the possibilities to identify photon--induced background was published previously. An 18-fold segmented prototype detector was tested and its performance compared with Monte Carlo predictions. The detector performed well and the agreement with the Monte Carlo is excellent.

  5. The 12C* Hoyle state in the inelastic 12C + 12C reaction and in 24Mg* decay

    NASA Astrophysics Data System (ADS)

    Morelli, L.; Bruno, M.; D'Agostino, M.; Baiocco, G.; Gulminelli, F.; Abbondanno, U.; Barlini, S.; Bini, M.; Casini, G.; Cinausero, M.; Degerlier, M.; Fabris, D.; Gramegna, F.; Mabiala, J.; Marchi, T.; Olmi, A.; Pasquali, G.; Piantelli, S.; Valdré, S.

    2016-08-01

    The reaction 12C + 12C at 95 MeV has been studied at the Legnaro Laboratories of INFN with the GARFIELD + RCo apparatus. Data have been analyzed in order to investigate the decay of the Hoyle state of 12C*. Two different data selections have been made. The first one corresponds to peripheral binary collisions where the quasi-projectile is excited to the Hoyle state and the target has been left in the ground state. The second selection allows for studying central events with the formation of a 24Mg* and the Hoyle state is obtained as a step of the decay chain. The characteristics of the Hoyle state decay are very similar in the two samples and point to a mainly sequential decay through the population of an intermediate 8Begs, with a small contribution (˜1.1%) from simultaneous three α-particle processes.

  6. Neutron-rich isotope production using a uranium carbide - carbon nanotubes SPES target prototype

    NASA Astrophysics Data System (ADS)

    Corradetti, S.; Biasetto, L.; Manzolaro, M.; Scarpa, D.; Carturan, S.; Andrighetto, A.; Prete, G.; Vasquez, J.; Zanonato, P.; Colombo, P.; Jost, C. U.; Stracener, D. W.

    2013-05-01

    The SPES (Selective Production of Exotic Species) project, under development at the Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro (INFN-LNL), is a new-generation Isotope Separation On-Line (ISOL) facility for the production of radioactive ion beams by means of the proton-induced fission of uranium. In the framework of the research on the SPES target, seven uranium carbide discs, obtained by reacting uranium oxide with graphite and carbon nanotubes, were irradiated with protons at the Holifield Radioactive Ion Beam Facility (HRIBF) of Oak Ridge National Laboratory (ORNL). In the following, the yields of several fission products obtained during the experiment are presented and discussed. The experimental results are then compared to those obtained using a standard uranium carbide target. The reported data highlights the capability of the new type of SPES target to produce and release isotopes of interest for the nuclear physics community.

  7. Optimisation of the usage of LHC and local computing resources in a multidisciplinary physics department hosting a WLCG Tier-2 centre

    NASA Astrophysics Data System (ADS)

    Barberis, Stefano; Carminati, Leonardo; Leveraro, Franco; Mazza, Simone Michele; Perini, Laura; Perlz, Francesco; Rebatto, David; Tura, Ruggero; Vaccarossa, Luca; Villaplana, Miguel

    2015-12-01

    We present the approach of the University of Milan Physics Department and the local unit of INFN to allow and encourage the sharing among different research areas of computing, storage and networking resources (the largest ones being those composing the Milan WLCG Tier-2 centre and tailored to the needs of the ATLAS experiment). Computing resources are organised as independent HTCondor pools, with a global master in charge of monitoring them and optimising their usage. The configuration has to provide satisfactory throughput for both serial and parallel (multicore, MPI) jobs. A combination of local, remote and cloud storage options are available. The experience of users from different research areas operating on this shared infrastructure is discussed. The promising direction of improving scientific computing throughput by federating access to distributed computing and storage also seems to fit very well with the objectives listed in the European Horizon 2020 framework for research and development.

  8. Accelerator-based analytical technique in the evaluation of some Nigeria’s natural minerals: Fluorite, tourmaline and topaz

    NASA Astrophysics Data System (ADS)

    Olabanji, S. O.; Ige, O. A.; Mazzoli, C.; Ceccato, D.; Akintunde, J. A.; De Poli, M.; Moschini, G.

    2005-10-01

    For the first time, the complementary accelerator-based analytical technique of PIXE and electron microprobe analysis (EMPA) were employed for the characterization of some Nigeria's natural minerals namely fluorite, tourmaline and topaz. These minerals occur in different areas in Nigeria. The minerals are mainly used as gemstones and for other scientific and technological applications and therefore are very important. There is need to characterize them to know the quality of these gemstones and update the geochemical data on them geared towards useful applications. PIXE analysis was carried out using the 1.8 MeV collimated proton beam from the 2.5 MV AN 2000 Van de Graaff accelerator at INFN, LNL, Legnaro, Padova, Italy. The novel results which show many elements at different concentrations in these minerals are presented and discussed.

  9. Characterization of the 80-mm diameter Hamamatsu PMTs for the KM3NeT project

    SciTech Connect

    Aiello, S.; Giordano, V.; Leonora, E.; Classen, L.; Reubelt, J.; Peek, H.; Visser, E.; Samtleben, D.; Kalekin, Oleg Collaboration: KM3NeT Collaboration

    2014-11-18

    The optical module designed for the KM3NeT project consists of 31 photomultipliers of 3-inch diameter housed into a 17-inch diameter glass sphere. A proposed photomultiplier was the R12199-02 Hamamatsu 80-mm diameter. 203 of such PMTs have been delivered from Hamamatsu and tested by the KM3NeT groups of NIKHEF-Amsterdam, ECAP-Erlangen and INFN-Catania. Tests have been performed to measure the main parameters, such as gain, transit time spread, dark pulses rate, fraction of spurious pulses, quantum efficiency and effective photocathode size. The main results matched with the requirements of the project. Methods and results are presented in this report.

  10. PIXE microbeam analysis of the metallic debris release around endosseous implants

    NASA Astrophysics Data System (ADS)

    Buso, G. P.; Galassini, S.; Moschini, G.; Passi, P.; Zadro, A.; Uzunov, N. M.; Doyle, B. L.; Rossi, P.; Provencio, P.

    2005-10-01

    The mechanical friction that occurs during the surgical insertion of endosseous implants, both in dentistry and orthopaedics, may cause the detachment of metal debris which are dislodged into the peri-implant tissues and can lead to adverse clinical effects. This phenomenon more likely happens with coated or roughened implants that are the most widely employed. In the present study were studied dental implants screws made of commercially pure titanium and coated using titanium plasma-spray (TPS) technique. The implants were inserted in the tibia of rabbits, and removed "en bloc" with the surrounding bone after one month. After proper processing and mounting on plastic holders, samples from bones were analysed by EDXRF setup at of National Laboratories of Legnaro, INFN, Italy, and consequently at 3 MeV proton microbeam setup at Sandia National Laboratories. Elemental maps were drawn, showing some occasional presence of metal particles in the peri-implant bone.

  11. On-line test using multi-foil SiC target at iThemba LABS

    NASA Astrophysics Data System (ADS)

    Monetti, A.; Bark, R. A.; Andrighetto, A.; Beukes, P.; Conradie, J. L.; Corradetti, S.; Fourie, D.; Lussi, C.; Manzolaro, M.; Meneghetti, G.; Prete, G.; Rossignoli, M.; Scarpa, D.; Van Schalkwyk, P.; Stoddart, N.; Vasquez, J.

    2016-06-01

    In a collaboration between the INFN-SPES project and iThemba LABS, an on-line test of the power dissipation of a multi-slice target concept for radioactive-ion beam production has been performed. Using the 66MeV proton beam from the iThemba LABS Separated Sector Cyclotron, a total power of 4kW was deposited in the target complex, consisting of 13 Silicon Carbide (SiC) discs of about 1 millimetre thickness housed in a graphite cylinder. The results of the measurements fully validate thermal FEM simulations and confirm that the multi-foil target system is a reliable and affordable device for second-generation ISOL-RIB facilities like SPES.

  12. Comparison between off-resonance and electron Bernstein waves heating regime in a microwave discharge ion source.

    PubMed

    Castro, G; Mascali, D; Romano, F P; Celona, L; Gammino, S; Lanaia, D; Di Giugno, R; Miracoli, R; Serafino, T; Di Bartolo, F; Gambino, N; Ciavola, G

    2012-02-01

    A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del Sud of INFN, Catania has been used to compare the traditional electron cyclotron resonance (ECR) heating with an innovative mechanisms of plasma ignition based on the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma electromagnetic-to-electrostatic wave conversion and they are absorbed by the plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at particular frequencies enabled us to reach densities much larger than the cutoff ones. Evidences of EBW generation and absorption together with X-ray emissions due to high energy electrons will be shown. A characterization of the discharge heating process in MDISs as a generalization of the ECR heating mechanism by means of ray tracing will be shown in order to highlight the fundamental physical differences between ECR and EBW heating. PMID:22380300

  13. Salerno Exultet: its characterization by Raman and PIXE-α analyses

    NASA Astrophysics Data System (ADS)

    Bicchieri, Marina; Nardone, Michele; Pappalardo, Giuseppe; Pappalardo, Lighea; Romano, Francesco P.; Russo, Pio A.; Sodo, Armida

    2001-10-01

    Two non-destructive techniques, Raman spectroscopy and particle induced x-ray emission spectrometry, were used for a compete connotation of the Salerno Exultet, an illuminated parchment dated back to 13th century. The Salerno Exultet exhibits several areas which have underdone restoration treatments during the years. The complete connotation of this masterpiece was necessary in order to identify and to distinguish the original and the added pigments. Owing to its dimensions, it has been impossible to analyze the Salerno Exultet directly under the microscope of our Micro- Raman spectrometer. We have therefore used optical fibers connected to a three axis micro-positioned measurement head mounted on a large metal frame. PIXE analysis was performed using the portable instrumentation set up by the INFN-LANDIS Laboratory, Catania, Italy. The combination of these two complementary techniques allowed us to reveal a palette formed by lapis-lazuli, cinnabar, verdigris, earths organic lakes and chalk.

  14. Recent developments of ion beam induced luminescence at the external scanning microbeam facility of the LABEC laboratory in Florence

    NASA Astrophysics Data System (ADS)

    Colombo, E.; Calusi, S.; Cossio, R.; Giuntini, L.; Giudice, A. Lo; Mandò, P. A.; Manfredotti, C.; Massi, M.; Mirto, F. A.; Vittone, E.

    2008-04-01

    A new ionoluminescence (IL) apparatus has been successfully installed at the external scanning microbeam facility of the 3 MV Tandetron accelerator of the INFN LABEC in Firenze; the apparatus for photon detection has been fully integrated in the existing ion beam analysis (IBA) set-up, for the simultaneous acquisition of IL and PIXE/PIGE/BS spectra and maps. The potential of the new set-up is illustrated in this paper by some results extracted by the analysis of art objects and advanced semiconductor materials. In particular, the adequacy of the new IBA set-up in the field of cultural heritage is pointed out by the coupled PIXE/IL micro-analysis of a lapis lazuli stone; concerning applications in material science, IL spectra from a N doped diamond sample were acquired and compared with CL analyses to evaluate the relevant sensitivities and the effect of ion damage.

  15. Women Physicists in the European Union : how Brussels is moving toward gender equality

    NASA Astrophysics Data System (ADS)

    Pancheri, Giulia

    2008-04-01

    The policies of the European Union towards gender equality in science occupation will be discussed along three aspects: 1. Current statistics recently published by the EU will be illustrated with some comparison with similar US statistics. The latest recommendations of the Helsinki group will be presented, together with the conclusions of the Women in Science meetings organized by the EU. 2. The implementation of these recommendations will be illustrated by this speaker's experience both as independent expert for Physics Research Programs for the European Commission for the last 10 years, as well as from the point of view of having been European Coordinator of three Research Networks in Theoretical Physics from 1992 until 2006: the impact of this on young women students will be described. 3. National policies enforced through the Equal Opportunity Committees will be illustrated, with the specific case of the Affirmative Actions of Italian INFN Equal Opportunity Committe and their impact on hiring and promotion of women physicists.

  16. Neutron-Rich Isotope Production Using a Uranium Carbide Carbon Nanotubes SPES Target Prototype

    SciTech Connect

    Corradetti, Stefano; Biasetto, Lisa; Manzolaro, Mattia; Scarpa, Daniele; Carturan, S.; Andrighetto, Alberto; Prete, Gianfranco; Vasquez, Jose L; Zanonato, P.; Colombo, P.; Jost, Carola; Stracener, Daniel W

    2013-01-01

    The SPES (Selective Production of Exotic Species) project, under development at the Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro (INFN-LNL), is a new-generation Isotope Separation On-Line (ISOL) facility for the production of radioactive ion beams by means of the proton-induced fission of uranium. In the framework of the research on the SPES target, seven uranium carbide discs, obtained by reacting uranium oxide with graphite and carbon nanotubes, were irradiated with protons at the Holifield Radioactive Ion Beam Facility (HRIBF) of Oak Ridge National Laboratory (ORNL). In the following, the yields of several fission products obtained during the experiment are presented and discussed. The experimental results are then compared to those obtained using a standard uranium carbide target. The reported data highlights the capability of the new type of SPES target to produce and release isotopes of interest for the nuclear physics community.

  17. Multiloop string vertices from the path integral

    NASA Astrophysics Data System (ADS)

    Bochicchio, M.; Lerda, A.

    1989-02-01

    We derive the multiloop vertices for the bosonic string using path integral methods and establish a precise equivalence between the functional approach to string perturbation theory and the operator formalism on Riemann surfaces recently developed by various authors. One of us (A.L.) would like to thank P. Di Vecchia and S. Sciuto for helpful discussions and INFN, Sezione di Torino, for the kind hospitality extended to him during the completion of this work. The work of M.B. was partially supported by the National Science Foundation under Grant NSF-PHY85-07627. The work of A.L. was partially supported by the US Department of Energy under grant DE-AC02-76ER03069.

  18. Recent developments on techniques for differential phase imaging at the medical beamline of ELETTRA

    NASA Astrophysics Data System (ADS)

    Arfelli, F.; Pelliccia, D.; Cedola, A.; Astolfo, A.; Bukreeva, I.; Cardarelli, P.; Dreossi, D.; Lagomarsino, S.; Longo, R.; Rigon, L.; Sodini, N.; Menk, R. H.

    2013-06-01

    Over the last decade different phase contrast approaches have been exploited at the medical beamline SYRMEP of the synchrotron radiation facility Elettra in Trieste, Italy. In particular special focus has been drawn to analyzer based imaging and the associated imaging theory and processing. Analyzer based Imaging (ABI) and Diffraction Enhanced Imaging (DEI) techniques have been successfully applied in several biomedical applications. Recently it has been suggested to translate the acquired knowledge in this field towards a Thomson Backscattering Source (TBS), which is presently under development at the Frascati National Laboratories of INFN (Istituto Nazionale di Fisica Nucleare) in Rome, Italy. Such source is capable of producing intense and quasi-monochromatic hard X-ray beams. For the technical implementation of biomedical phase imaging at the TBS a grating interferometer for differential phase contrast imaging has been designed and successfully tested at SYRMEP beamline.

  19. Proof of concept of an imaging system demonstrator for PET applications with SiPM

    NASA Astrophysics Data System (ADS)

    Morrocchi, Matteo; Marcatili, Sara; Belcari, Nicola; Giuseppina Bisogni, Maria; Collazuol, Gianmaria; Ambrosi, Giovanni; Santoni, Cristiano; Corsi, Francesco; Foresta, Maurizio; Marzocca, Cristoforo; Matarrese, Gianvito; Sportelli, Giancarlo; Guerra, Pedro; Santos, Andres; Del Guerra, Alberto

    2013-08-01

    A PET imaging system demonstrator based on LYSO crystal arrays coupled to SiPM matrices is under construction at the University and INFN of Pisa. Two SiPM matrices, composed of 8×8 SiPM pixels, and 1,5 mm pitch, have been coupled one to one to a LYSO crystals array and read out by a custom electronics system. front-end ASICs were used to read 8 channels of each matrix. Data from each front-end were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port for the storage and off-line data processing. In this paper we show the first preliminary tomographic image of a point-like radioactive source acquired with part of the two detection heads in time coincidence.

  20. DAMA/LIBRA-phase1 results and perspectives of the phase2

    NASA Astrophysics Data System (ADS)

    Bernabei, R.; Belli, P.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; He, H. L.; Incicchitti, A.; Kuang, H. H.; Ma, X. H.; Montecchia, F.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

    2016-07-01

    The DAMA/LIBRA experiment (˜ 250 kg of highly radio-pure NaI(Tl)) is running deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N. Here we briefly recall the results obtained in its first phase of measurements (DAMA/LIBRA-phase1; total exposure: 1.04 ton × yr). DAMA/LIBRA-phase1 and the former DAMA/NaI (cumulative exposure: 1.33 ton × yr) give evidence at 9.3 σ C.L. for the presence of DM particles in the galactic halo by exploiting the model-independent DM annual modulation signature. No systematic or side reaction able to mimic the exploited DM signature has been found or suggested by anyone over more than a decade. At present DAMA/LIBRA-phase2 is running with increased sensitivity.

  1. Comparison between off-resonance and electron Bernstein waves heating regime in a microwave discharge ion source

    SciTech Connect

    Castro, G.; Di Giugno, R.; Miracoli, R.; Mascali, D.; Romano, F. P.; Celona, L.; Gammino, S.; Lanaia, D.; Ciavola, G.; Serafino, T.; Di Bartolo, F.; Gambino, N.

    2012-02-15

    A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del Sud of INFN, Catania has been used to compare the traditional electron cyclotron resonance (ECR) heating with an innovative mechanisms of plasma ignition based on the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma electromagnetic-to-electrostatic wave conversion and they are absorbed by the plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at particular frequencies enabled us to reach densities much larger than the cutoff ones. Evidences of EBW generation and absorption together with X-ray emissions due to high energy electrons will be shown. A characterization of the discharge heating process in MDISs as a generalization of the ECR heating mechanism by means of ray tracing will be shown in order to highlight the fundamental physical differences between ECR and EBW heating.

  2. Online monitoring for the CDF Run II experiment and the remote operation facilities

    SciTech Connect

    Arisawa, T.; Fabiani, D.; Hirschbuehl, D.; Ikado, K.; Kubo, T.; Kusakabe, Y.; Maeshima, K.; Naganoma, J.; Nakamura, K.; Plager, C.; Schmidt, E.; /Fermilab /INFN, Pisa /Karlsruhe U.

    2007-01-01

    The foundation of the CDF Run II online event monitoring framework, placed well before the physics runs start, allowed to develop coherent monitoring software across all the different subsystems which consequently made maintenance and operation simple and efficient. Only one shift person is needed to monitor the entire CDF detector, including the trigger system. High data quality check is assured in real time and well defined monitoring results are propagated coherently to offline datasets used for physics analyzes. We describe the CDF Run II online event monitoring system and operation, with emphasis on the remote monitoring shift operation started since November 2006 with Pisa-INFN as pilot Institution and exploiting the WEB based access to the data.

  3. Plasma density characterization at SPARC_LAB through Stark broadening of Hydrogen spectral lines

    NASA Astrophysics Data System (ADS)

    Filippi, F.; Anania, M. P.; Bellaveglia, M.; Biagioni, A.; Chiadroni, E.; Cianchi, A.; Di Giovenale, D.; Di Pirro, G.; Ferrario, M.; Mostacci, A.; Palumbo, L.; Pompili, R.; Shpakov, V.; Vaccarezza, C.; Villa, F.; Zigler, A.

    2016-09-01

    Plasma-based acceleration techniques are of great interest for future, compact accelerators due to their high accelerating gradient. Both particle-driven and laser-driven Plasma Wakefield Acceleration experiments are foreseen at the SPARC_LAB Test Facility (INFN National Laboratories of Frascati, Italy), with the aim to accelerate high-brightness electron beams. In order to optimize the efficiency of the acceleration in the plasma and preserve the quality of the accelerated beam, the knowledge of the plasma electron density is mandatory. The Stark broadening of the Hydrogen spectral lines is one of the candidates used to characterize plasma density. The implementation of this diagnostic for plasma-based experiments at SPARC_LAB is presented.

  4. Reaction dynamics induced by the radioactive ion beam {sup 7}Be on medium-mass and heavy targets

    SciTech Connect

    Mazzocco, M. Stefanini, C.; Strano, E.; Torresi, D.; Lay, J. A.; Molini, P.; Soramel, F.; Boiano, A.; Parascandolo, C.; Pierroutsakou, D.; Di Meo, P.; Boiano, C.; La Commara, M.; Sandoli, M.; Silvestri, R.; Manea, C.; Nicoletto, M.; Acosta, L.; Fernandez-Garcia, J. P.; Glodariu, T.; and others

    2015-10-15

    We studied the reaction dynamics induced at Coulomb barrier energies by the weakly-bound Radioactive Ion Beam {sup 7}Be (S{sub α} = 1.586 MeV) on medium-mass ({sup 58}Ni) and heavy ({sup 208}Pb) targets. The experiments were performed at INFN-LNL (Italy), where a 2-3×10{sup 5} pps {sup 7}Be secondary beam was produced with the RIB in-flight facility EXOTIC. Charged reaction products were detected by means of high-granularity silicon detectors in rather wide angular ranges. The contribution presents an up-to-date status of the data analysis and theoretical interpretation for both systems.

  5. Jefferson Laboratory Hall A SuperBigBite spectrometer GEM readout scheme

    NASA Astrophysics Data System (ADS)

    Camsonne, Alexandre; Hall A SuperBigBite Collaboration

    2015-10-01

    The SuperBigBite spectrometer at Jefferson Laboratory in Hall A will rely on Gas Electron Multiplier trackers to achieve the required luminosity for large momentum transfer experiments. The readout electronics is based on the APV25 ASIC and the INFN VME board Multi Purpose Digitizer (MPD) Board. By using the optical readout of readout of the boards, all boards can be readout in parallel effectively increasing the data bandwidth for one crate by more than a factor of 10. With such scheme the readout of several samples become possible and background rejection can be applied to reduce the large quantity of data due to the high occupancy of detector before it is recorded. This special readout scheme based on the JLab electronics will be presented along with the online data reduction strategy for the GEM data.

  6. Site Studies for the SuperB Collider and Synchrotron Radiation Facility Project

    SciTech Connect

    Tomassini, S.; Biagini, M.E.; Raimondi, P.; Sanelli, C.; Bolzon, B.; Deleglise, G.; Jeremie, A.; Seeman, J.; /SLAC

    2012-04-26

    The SuperB complex project aims at the construction of a very high luminosity (10{sup 36} cm{sup -2}s{sup -1}) asymmetric e{sup +}e{sup -} B-factory and a few X-ray synchrotron beam lines (SR). The project has been recently approved by the Italian Government as part of the National Research Plan. The Tor Vergata University location has been chosen and a Consortium among INFN, University of Rome II Tor Vergata and the Research Ministry is being signed, allowing for the constitution of the 'Cabibbo Laboratory', where the SuperB project will be hosted. This paper presents and describes the status of the preliminary design of the site layout, related issues for the chosen site and the preliminary ground motion (GM) measurement results.

  7. Particle Dark Matter in the galactic halo: results from DAMA/LIBRA

    SciTech Connect

    Bernabei, R.; Belli, P.; Nozzoli, F.; Montecchia, F.; Cappella, F.; D'Angelo, A.; Incicchitti, A.; Presperi, D.; Cerulli, R.; Dai, C. J.; He, H. L.; Kuang, H. H.; Ma, X. H.; Sheng, X. D.

    2010-02-10

    The DAMA/LIBRA experiment at the Gran Sasso National Laboratory of the I.N.F.N. has confirmed with higher sensitivity the model independent evidence for Dark Matter (DM) particles in the galactic halo obtained by the former DAMA/NaI experiment by investigating the DM annual modulation signature. Considering the data collected by DAMA/LIBRA together with the data collected by the former DAMA/NaI (cumulative exposure of 0.82 tonxyr) a confidence level of 8.2 sigma has been achieved. The experiment is in data taking; a first upgrading of the set-up has been carried out in Spetember 2008 and a second one--aiming to decrease the experimental energy threshold--is foreseen in September 2010.

  8. Extreme Energy Events Project: Construction of the detectors and installation in Italian High Schools

    NASA Astrophysics Data System (ADS)

    Abbrescia, M.; An, S.; Antolini, R.; Badalà, A.; Baldini Ferroli, R.; Bencivenni, G.; Blanco, F.; Bressan, E.; Chiavassa, A.; Chiri, C.; Cifarelli, L.; Cindolo, F.; Coccia, E.; de Pasquale, S.; di Giovanni, A.; D'Incecco, M.; Fabbri, F. L.; Frolov, V.; Garbini, M.; Gustavino, C.; Hatzifotiadou, D.; Imponente, G.; Kim, J.; La Rocca, P.; Librizzi, F.; Maggiora, A.; Menghetti, H.; Miozzi, S.; Moro, R.; Panareo, M.; Pappalardo, G. S.; Piragino, G.; Riggi, F.; Romano, F.; Sartorelli, G.; Sbarra, C.; Selvi, M.; Serci, S.; Williams, C.; Zichichi, A.; Zuyeuski, R.

    2008-04-01

    The EEE Project, conceived by its leader Antonino Zichichi, aims to detect Extreme Energy Events of cosmic rays with an array of muon telescopes distributed over the Italian territory. The Project involves Italian High Schools in order to introduce young people to Physics, also countervailing the recent crisis of university scientific classes inscriptions. The detectors for the EEE telescopes are Multigap Resistive Plate Chambers (MRPC) and have been constructed by teams of High School students who went in shift at the CERN laboratories. The mechanics and the electronics were developed by groups of researchers from CERN, the Italian Centro Fermi and INFN. The first group of schools of the EEE Project has inaugurated their telescopes recently. A status report of the Project and the preliminary results are presented.

  9. Far-infrared synchrotron radiation spectroscopy of solids in normal and extreme conditions

    NASA Astrophysics Data System (ADS)

    Piccinini, M.; Cestelli Guidi, M.; Marcelli, A.; Calvani, P.; Burattini, E.; Nucara, A.; Postorino, P.; Sacchetti, A.; Arcangeletti, E.; Sheregii, E.; Polit, J.; Kisiel, A.

    2005-01-01

    New opportunities in solid-state physics are offered by SINBAD (Synchrotron INfrared Beamline At DAFNE), the infrared beamline operational at DANE, the storage ring of the Laboratori Nazionali di Frascati of the INFN. During 2003 several experiments, including those supported by the European TARI program, have been successfully performed at SINBAD. In this work we present the preliminary results of high resolution far infrared reflectivity data collected in different ZnxCdyHg(1-x-y)Te quaternary alloys as a function of temperature. The first far-IR investigation of Colossal Magnetoresistance manganites at high pressures, using a diamond anvil cell is also presented. Indeed, FT-IR spectroscopy is a powerful tool for the investigation of insulating-to-metal transitions and charge ordering phenomena that may occur in transition metal oxides.

  10. SPECIAL SEMINAR - The NOTTE experiment, or how to become a Total Solar Eclipse chaser

    SciTech Connect

    2011-02-08

    The NOTTE experiment (Neutrino Oscillations with Telescope during Total Eclipse) aims at searching for visible photons emitted through a possible radiative decay of solar neutrinos. The experiment and the expeditions organized by a group of physicists and astrophysicists from INFN and INAF Bologna hunting for Total Solar Eclipses from 1998 to 2006 wil be described. The results of observations performed during total solar eclipse expeditions in 2001 (Zambia) and 2006 (Sahara desert, Libya) are presented and a beautiful photo gallery will be shown. Other peculiar observations that can be made during a solar eclipse are also illustrated. The seminar will be followed by a brief presentation of future camps for solar eclipse chasers and scientists organized in 2008 in Russia, Kazakhstan, China and Mongolia, in 2009 in Shanghai and on the Easter Island in 2010.

  11. Accurate on line measurements of low fluences of charged particles

    NASA Astrophysics Data System (ADS)

    Palla, L.; Czelusniak, C.; Taccetti, F.; Carraresi, L.; Castelli, L.; Fedi, M. E.; Giuntini, L.; Maurenzig, P. R.; Sottili, L.; Taccetti, N.

    2015-03-01

    Ion beams supplied by the 3MV Tandem accelerator of LABEC laboratory (INFN-Firenze), have been used to study the feasibility of irradiating materials with ion fluences reproducible to about 1%. Test measurements have been made with 7.5 MeV 7Li2+ beams of different intensities. The fluence control is based on counting ions contained in short bursts generated by chopping the continuous beam with an electrostatic deflector followed by a couple of adjustable slits. Ions are counted by means of a micro-channel plate (MCP) detecting the electrons emitted from a thin layer of Al inserted along the beam path in between the pulse defining slits and the target. Calibration of the MCP electron detector is obtained by comparison with the response of a Si detector.

  12. Heat Deposit Calculation in Spallation Unit

    NASA Astrophysics Data System (ADS)

    Karmanov, F. I.; Travleev, A. A.; Latysheva, L. N.; Vecchi, M.

    2001-11-01

    The present study concerns the calculation of the heat deposition in one of the EAP-80 basic units - the spallation module including the beam window, lead-bismuth spallation target and primary liquid metal cooling system. It is assumed that the model of sub-critical reactor under investigation is based on ANSALDO-INFN-ENEA-CRS4 reference configuration1. The calculation have been done by means of a couple computer codes: INCC 2 and GEANT3.21 3. These codes have been preliminary tested on the experimental data obtained in 4 for the case of interaction of proton beam and lead-bismuth targets at the energy Ep= 800MeV which is close to energy range relevant for ADS configuration.

  13. Background modeling for the GERDA experiment

    NASA Astrophysics Data System (ADS)

    Becerici-Schmidt, N.; Gerda Collaboration

    2013-08-01

    The neutrinoless double beta (0νββ) decay experiment GERDA at the LNGS of INFN has started physics data taking in November 2011. This paper presents an analysis aimed at understanding and modeling the observed background energy spectrum, which plays an essential role in searches for a rare signal like 0νββ decay. A very promising preliminary model has been obtained, with the systematic uncertainties still under study. Important information can be deduced from the model such as the expected background and its decomposition in the signal region. According to the model the main background contributions around Qββ come from 214Bi, 228Th, 42K, 60Co and α emitting isotopes in the 226Ra decay chain, with a fraction depending on the assumed source positions.

  14. A steady-state high-temperature method for measuring thermal conductivity of refractory materials

    NASA Astrophysics Data System (ADS)

    Manzolaro, M.; Corradetti, S.; Andrighetto, A.; Ferrari, L.

    2013-05-01

    A new methodology and an instrumental setup for the thermal conductivity estimation of isotropic bulk graphite and different carbides at high temperatures are presented. The method proposed in this work is based on the direct measurement of temperature and emissivity on the top surface of a sample disc of known dimensions. Temperatures measured under steady-state thermal equilibrium are then used to estimate the thermal conductivity of the sample by making use of the inverse parameter estimation technique. Thermal conductivity values obtained in this way are then compared to the material data sheets and values found in literature. The reported work has been developed within the Research and Development framework of the SPES (Selective Production of Exotic Species) project at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro).

  15. Status of the Trasco Intense Proton Source and emittance measurements

    NASA Astrophysics Data System (ADS)

    Celona, L.; Ciavola, G.; Gammino, S.; Chines, F.; Presti, M.; Andò, L.; Guo, X. H.; Gobin, R.; Ferdinand, R.

    2004-05-01

    The Trasco Intense Proton Source (TRIPS) was installed at INFN-LNS in May 2000 and has been fully operational since the Fall of 2000; now the source fulfills all the requirements of the TRASCO (Trasmutazione Scorie) project. The proton beam intensity easily exceeds 40 mA at the operating voltage of 80 kV. A set of emittance measurements was carried out for different source conditions and confirmed the simulations performed with the AXCEL code: in all the cases the rms normalized emittance is well lower than the value required for the injection into the RFQ (0.2 π mm mrad); the results will be shown and discussed. Finally a beam reliability of 99.8% has been found during a long run test lasting over 142 h.

  16. A high precision calorimeter for the SOX experiment

    NASA Astrophysics Data System (ADS)

    Papp, L.; Agostini, M.; Altenmüller, K.; Appel, S.; Caminata, A.; Cereseto, R.; Di Noto, L.; Farinon, S.; Musenich, R.; Neumair, B.; Oberauer, L.; Pallavicini, M.; Schönert, S.; Testera, G.; Zavatarelli, S.

    2016-07-01

    The SOX (Short distance neutrino Oscillations with BoreXino) experiment is being built to discover or reject eV-scale sterile neutrinos by observing short baseline oscillations of active-to-sterile neutrinos [1]. For this purpose, a 100 kCi 144Ce-144Pr antineutrino generator (CeSOX) will be placed under the BOREXINO detector at the Laboratori Nazionali del Gran Sasso. Thanks to its large size and very low background, BOREXINO is an ideal detector to discover or reject eV-scale sterile neutrinos. To reach the maximal sensitivity, we aim at determining the neutrino flux emitted by the antineutrino generator with a < 1 % accuracy. With this goal, TU München and INFN Genova are developing a vacuum calorimeter, which is designed to measure the source-generated heat with high accuracy.

  17. Ultra-weak delayed luminescence in cancer research: a review of the results by the ARETUSA equipment.

    PubMed

    Scordino, Agata; Baran, Irina; Gulino, Marisa; Ganea, Constanta; Grasso, Rosaria; Niggli, J Hugo; Musumeci, Francesco

    2014-10-01

    The study of the photoinduced ultraweak photon emission in the optical wavelength range, namely the Delayed Luminescence, from human cells and tissues has an increasingly growing interest in view of its possible application in optical biopsy. Due to the low level, dedicated experimental set-up are necessary to reveal such photoluminescence signal. The paper reviews the results obtained in the field of cancer research, by using the experimental equipment for fast ultraweak luminescence analysis ARETUSA developed at the National Southern Laboratories of the National Nuclear Physics Institute (LNS-INFN), in Catania, Italy. Delayed Luminescence signals from normal and cancer cells are compared and the relationship between Delayed Luminescence and apoptosis is investigated.

  18. Neutron dosimetry at a high-energy electron-positron collider

    NASA Astrophysics Data System (ADS)

    Bedogni, Roberto

    Electron-positron colliders with energy of hundreds of MeV per beam have been employed for studies in the domain of nuclear and sub-nuclear physics. The typical structure of such a collider includes an LINAC, able to produce both types of particles, an accumulator ring and a main ring, whose diameter ranges from several tens to hundred meters and allows circulating particle currents of several amperes per beam. As a consequence of the interaction of the primary particles with targets, shutters, structures and barriers, a complex radiation environment is produced. This paper addresses the neutron dosimetry issues associated with the operation of such accelerators, referring in particular to the DAΦ NE complex, operative since 1997 at INFN-Frascati National Laboratory (Italy). Special attention is given to the active and passive techniques used for the spectrometric and dosimetric characterization of the workplace neutron fields, for radiation protection dosimetry purposes.

  19. Discovering forgeries of modern art by the 14C Bomb Peak

    NASA Astrophysics Data System (ADS)

    Caforio, L.; Fedi, M. E.; Mandò, P. A.; Minarelli, F.; Peccenini, E.; Pellicori, V.; Petrucci, F. C.; Schwartzbaum, P.; Taccetti, F.

    2014-01-01

    Exploiting the anomalous behaviour of the atmospheric radiocarbon concentration in the years after 1955 (so-called "Bomb Peak"), an alleged painting by Fernard Léger was unambiguously proven to be a fake just by dating the canvas support. Some art historians had questioned the authenticity of the painting, and their suspicions were fuelled by some scientific examinations of the paint materials (X-ray radiography, SEM-EDS), compared to those of another work unquestionably attributed to Léger. The decisive argument to prove that it was a fake was provided by the radiocarbon date obtained from a sample of canvas of the painting, using Accelerator Mass Spectrometry at the INFN-Labec laboratory in Florence. Beyond any doubt, the cotton plant from which the canvas was produced was cut no earlier than 1959, i.e. four years after Léger's death, thus definitely confirming the concerns of a fake.

  20. 3D monolithically stacked CMOS Active Pixel Sensors for particle position and direction measurements

    NASA Astrophysics Data System (ADS)

    Servoli, L.; Passeri, D.; Morozzi, A.; Magalotti, D.; Piperku, L.

    2015-01-01

    In this work we propose a 3D monolithically stacked, multi-layer detectors based on CMOS Active Pixel Sensors (APS) layers which allows at the same time accurate estimation of the impact point and of the incidence angle an ionizing particle. The whole system features two fully-functional CMOS APS matrix detectors, including both sensing area and control/signal elaboration circuitry, stacked in a monolithic device by means of Through Silicon Via (TSV) connections thanks to the capabilities of the CMOS vertical scale integration (3D-IC) 130 nm Chartered/Tezzaron technology. In order to evaluate the suitability of the two layer monolithic active pixel sensor system to reconstruct particle tracks, tests with proton beams have been carried out at the INFN LABEC laboratories in Florence (Italy) with 3 MeV proton beam.

  1. Mu2e transport solenoid prototype tests results

    DOE PAGES

    Lopes, Mauricio L.; G. Ambrosio; DiMarco, J.; Evbota, D.; Feher, S.; Friedsam, H.; Galt, A.; Hays, S.; Hocker, J.; Kim, M. J.; et al

    2016-02-08

    The Fermilab Mu2e experiment has been developed to search for evidence of charged lepton flavor violation through the direct conversion of muons into electrons. The transport solenoid is an s-shaped magnet which guides the muons from the source to the stopping target. It consists of fifty-two superconducting coils arranged in twenty-seven coil modules. A full-size prototype coil module, with all the features of a typical module of the full assembly, was successfully manufactured by a collaboration between INFN-Genoa and Fermilab. The prototype contains two coils that can be powered independently. In order to validate the design, the magnet went throughmore » an extensive test campaign. Warm tests included magnetic measurements with a vibrating stretched wire, electrical and dimensional checks. As a result, the cold performance was evaluated by a series of power tests as well as temperature dependence and minimum quench energy studies.« less

  2. Note: Enhanced production of He{sup +} from the Versatile Ion Source (VIS) in off-resonance configuration

    SciTech Connect

    Castro, G.; Mascali, D.; Celona, L.; Gammino, S.; Mazzaglia, M.; Neri, L.; Altana, C.; Ciavola, G.; Caliri, C.; Bartolo, F. Di; Lanaia, D.; Miracoli, R.; Torrisi, G.

    2014-09-15

    The Versatile Ion Source (VIS) is a microwave discharge ion source installed at INFN-LNS and here used as test-bench for the production of high intensity low emittance proton beams and for studies on plasma physics. A series of measurements have been carried out with VIS in order to test the source with light ions. In particular a He{sup +} beam has been characterized in terms of plasma discharge parameters. The experiment has been triggered by the observation of X-radiation emission from the plasma for some configuration of the magnetic field profile. The plasma electron energy distribution function is in fact modified when in some regions of the plasma chamber under-resonance discharge takes place, fulfilling the condition that allows the electromagnetic wave to electrostatic wave conversion. These tests allowed obtaining more than 50 mA of He{sup +} beams.

  3. Study of two- and multi-particle correlations in 12C+24Mg and 12C+208Pb reactions at E=35 AMeV

    NASA Astrophysics Data System (ADS)

    Quattrocchi, L.; Acosta, L.; Amorini, F.; Anzalone, A.; Auditore, L.; Berceanu, I.; Cardella, G.; Chbihi, A.; De Filippo, E.; Dell'Aquila, D.; Francalanza, L.; Gnoffo, B.; Grzeszczuk, A.; Lanzalone, G.; Lombardo, I.; Martel, I.; Minniti, T.; Norella, S.; Pagano, A.; Pagano, E. V.; Papa, M.; Pirrone, S.; Politi, G.; Porto, F.; Rizzo, F.; Rosato, E.; Russotto, P.; Trifirò, A.; Trimarchi, M.; Verde, G.; Veselsky, M.; Vigilante, M.

    2016-05-01

    Two and multi particle correlations from the decay of sources produced in 12C+24Mg and 12C+208Pb collisions at E=35 AMeV have been studied by using the forward part (1° < θlab < 30°) of the CHIMERA multi-detector. Correlations and invariant mass spectroscopy are used to explore simultaneous and sequential decays of resonances in light isotopes with Z˜3-6, produced in peripheral collisions via the break-up of excited quasi-projectiles. Among them we mention 5Li, 6Li, 6Be, 8Be and the astrophysically important state in 12C decaying into three alpha particles. Results and future perspectives at the INFN-LNS will be presented.

  4. Development of single-exposure, multidetector neutron spectrometers: the NESCOFI@BTF project.

    PubMed

    Bedogni, R; Gómez-Ros, J M; Bortot, D; Pola, A; Introini, M V; Esposito, A; Gentile, A; Mazzitelli, G; Buonomo, B

    2014-10-01

    NESCOFI@BTF is a 3-y project (2011-13) supported by the Scientific Commission 5 of INFN (Italy). The target is the development of neutron spectrometers similar to the Bonner spheres, in terms of response energy interval and accuracy, but able to determine the neutron spectrum in only one exposure. These devices embed multiple (10 to 30) thermal neutron detectors (TNDs) within a single moderator. Two prototypes, called SPherical SPectrometer (SP(2)) and cylindrical spectrometer (CYSP), have been set up. Whilst SP(2) has spherical geometry and nearly isotropic response, the CYSP has cylindrical geometry and is intended to be used as a directional spectrometer. Suitable active TNDs will be embedded in the final version of the devices. The resulting instruments could be used as real-time neutron spectrometers in neutron-producing facilities. This communication describes the design criteria, numerical analysis, experimental issues, state-of-the-art and future developments connected with the development of these instruments.

  5. Comparison between off-resonance and electron Bernstein waves heating regime in a microwave discharge ion source.

    PubMed

    Castro, G; Mascali, D; Romano, F P; Celona, L; Gammino, S; Lanaia, D; Di Giugno, R; Miracoli, R; Serafino, T; Di Bartolo, F; Gambino, N; Ciavola, G

    2012-02-01

    A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del Sud of INFN, Catania has been used to compare the traditional electron cyclotron resonance (ECR) heating with an innovative mechanisms of plasma ignition based on the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma electromagnetic-to-electrostatic wave conversion and they are absorbed by the plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at particular frequencies enabled us to reach densities much larger than the cutoff ones. Evidences of EBW generation and absorption together with X-ray emissions due to high energy electrons will be shown. A characterization of the discharge heating process in MDISs as a generalization of the ECR heating mechanism by means of ray tracing will be shown in order to highlight the fundamental physical differences between ECR and EBW heating.

  6. Comparison between off-resonance and electron Bernstein waves heating regime in a microwave discharge ion sourcea)

    NASA Astrophysics Data System (ADS)

    Castro, G.; Mascali, D.; Romano, F. P.; Celona, L.; Gammino, S.; Lanaia, D.; Di Giugno, R.; Miracoli, R.; Serafino, T.; Di Bartolo, F.; Gambino, N.; Ciavola, G.

    2012-02-01

    A microwave discharge ion source (MDIS) operating at the Laboratori Nazionali del Sud of INFN, Catania has been used to compare the traditional electron cyclotron resonance (ECR) heating with an innovative mechanisms of plasma ignition based on the electrostatic Bernstein waves (EBW). EBW are obtained via the inner plasma electromagnetic-to-electrostatic wave conversion and they are absorbed by the plasma at cyclotron resonance harmonics. The heating of plasma by means of EBW at particular frequencies enabled us to reach densities much larger than the cutoff ones. Evidences of EBW generation and absorption together with X-ray emissions due to high energy electrons will be shown. A characterization of the discharge heating process in MDISs as a generalization of the ECR heating mechanism by means of ray tracing will be shown in order to highlight the fundamental physical differences between ECR and EBW heating.

  7. Test of a LYSO calorimeter prototype readout by large-area Silicon PhotoMultipliers

    NASA Astrophysics Data System (ADS)

    Guffanti, D.; Berra, A.; Lietti, D.; Prest, M.; Bonvicini, V.; Vallazza, E.; Cecchi, C.; Germani, S.; Lubrano, P.; Manoni, E.; Rossi, A.

    2014-06-01

    Large area Silicon PhotoMultipliers (SiPMs) are the new frontier of the development of readout systems for scintillating detectors. A SiPM consists of a matrix of parallel-connected silicon micropixels operating in limited Geiger-Muller avalanche mode, and thus working as independent photon counters with a very high gain (˜ 106). This contribution presents the performance in terms of linearity and energy resolution of an electromagnetic homogeneous calorimeter composed of 9 ˜ 18X0 LYSO crystals. The crystals were readout by 36 4 × 4 mm2 SiPMs (4 for each crystal) produced by FBK-irst. This calorimeter has been tested at the Beam Test Facility at the INFN laboratories in Frascati with a single- and multi-particle electron beam in the 100-500 MeV energy range.

  8. Underground nuclear astrophysics: Why and how

    NASA Astrophysics Data System (ADS)

    Best, A.; Caciolli, A.; Fülöp, Zs.; Gyürky, Gy.; Laubenstein, M.; Napolitani, E.; Rigato, V.; Roca, V.; Szücs, T.

    2016-04-01

    The goal of nuclear astrophysics is to measure cross-sections of nuclear physics reactions of interest in astrophysics. At stars temperatures, these cross-sections are very low due to the suppression of the Coulomb barrier. Cosmic-ray-induced background can seriously limit the determination of reaction cross-sections at energies relevant to astrophysical processes and experimental setups should be arranged in order to improve the signal-to-noise ratio. Placing experiments in underground sites, however, reduces this background opening the way towards ultra low cross-section determination. LUNA (Laboratory for Underground Nuclear Astrophysics) was pioneer in this sense. Two accelerators were mounted at the INFN National Laboratories of Gran Sasso (LNGS) allowing to study nuclear reactions close to stellar energies. A summary of the relevant technology used, including accelerators, target production and characterisation, and background treatment is given.

  9. The MAGNEX spectrometer: Results and perspectives

    NASA Astrophysics Data System (ADS)

    Cappuzzello, F.; Agodi, C.; Carbone, D.; Cavallaro, M.

    2016-06-01

    This review discusses the main achievements and future perspectives of the MAGNEX spectrometer at the INFN-LNS laboratory in Catania (Italy). MAGNEX is a large-acceptance magnetic spectrometer for the detection of the ions emitted in nuclear collisions below Fermi energy. In the first part of the paper an overview of the MAGNEX features is presented. The successful application to the precise reconstruction of the momentum vector, to the identification of the ion masses and to the determination of the transport efficiency is demonstrated by in-beam tests. In the second part, an overview of the most relevant scientific achievements is given. Results from nuclear elastic and inelastic scattering as well as from transfer and charge-exchange reactions in a wide range of masses of the colliding systems and incident energies are shown. The role of MAGNEX in solving old and new puzzles in nuclear structure and direct reaction mechanisms is emphasized. One example is the recently observed signature of the long searched Giant Pairing Vibration. Finally, the new challenging opportunities to use MAGNEX for future experiments are briefly reported. In particular, the use of double charge-exchange reactions toward the determination of the nuclear matrix elements entering in the expression of the half-life of neutrinoless double beta decay is discussed. The new NUMEN project of INFN, aiming at these investigations, is introduced. The challenges connected to the major technical upgrade required by the project in order to investigate rare processes under high fluxes of detected heavy ions are outlined.

  10. High density plasmas and new diagnostics: An overview (invited).

    PubMed

    Celona, L; Gammino, S; Mascali, D

    2016-02-01

    One of the limiting factors for the full understanding of Electron Cyclotron Resonance Ion Sources (ECRISs) fundamental mechanisms consists of few types of diagnostic tools so far available for such compact machines. Microwave-to-plasma coupling optimisation, new methods of density overboost provided by plasma wave generation, and magnetostatic field tailoring for generating a proper electron energy distribution function, suitable for optimal ion beams formation, require diagnostic tools spanning across the entire electromagnetic spectrum from microwave interferometry to X-ray spectroscopy; these methods are going to be implemented including high resolution and spatially resolved X-ray spectroscopy made by quasi-optical methods (pin-hole cameras). The ion confinement optimisation also requires a complete control of cold electrons displacement, which can be performed by optical emission spectroscopy. Several diagnostic tools have been recently developed at INFN-LNS, including "volume-integrated" X-ray spectroscopy in low energy domain (2-30 keV, by using silicon drift detectors) or high energy regime (>30 keV, by using high purity germanium detectors). For the direct detection of the spatially resolved spectral distribution of X-rays produced by the electronic motion, a "pin-hole camera" has been developed also taking profit from previous experiences in the ECRIS field. The paper will give an overview of INFN-LNS strategy in terms of new microwave-to-plasma coupling schemes and advanced diagnostics supporting the design of new ion sources and for optimizing the performances of the existing ones, with the goal of a microwave-absorption oriented design of future machines.

  11. The EEE Project

    NASA Astrophysics Data System (ADS)

    Abbrescia, M.; An, S.; Antolini, R.; Badala, A.; Baldini Ferroli, R.; Bencivenni, G.; Blanco, F.; Bressan, E.; Chiavassa, A.; Chiri, C.; Cifarelli, L.; Cindolo, F.; Coccia, E.; de Pasquale, S.; di Giovanni, A.; d'Incecco, M.; Fabbri, F.L.; Frolov, V.; Garbini, M.; Gustavino, C.; Hatzifotiadou, D.; Imponente, G.; Kim, J.; La Rocca, P.; Librizzi, F.; Maggiora, A.; Menghetti, H.; Miozzi, S.; Moro, R.; Panareo, M.; Pappalardo, G.S.; Piragino, G.; Riggi, F.; Romano, F.; Sartorelli, G.; Sbarra, C.; Selvi, M.; Serci, S.; WIlliams, C.; Zichichi, A.; Zuyenski, R.

    The EEE (/Extreme Energy Event/) Project is an experiment for the study of very high-energy extensive air showers, actually starting in Italy. It is based on the detection of the shower muon component by means of a network of tracking detectors, installed in Italian High Schools. The Project, supported by the Ministero dell’Università e della Ricerca (MIUR), Istituto Nazionale di Fisica Nucleare (INFN), European Organization for Nuclear Research (CERN) and Museo Storico della Fisica e Centro Studi e Ricerche “E. Fermi” has been conceived by its leader Professor Antonino Zichichi. In its first phase the detector telescopes will be installed in 21 High Schools in 7 piloting cities all over Italy. The network will soon be heavily upgraded by increasing the number of High Schools and cities. The single tracking telescope is composed by 3 large (~ 2 m2 ) Multi-gap Resistive Plate Chambers (MRPC), realized with float glass electrodes. The use of particle detectors based on such MRPCs will allow to determine with a very high accuracy the direction of the axis of cosmic ray showers initiated by primaries of ultra-high energy, together with a high temporal resolution. The first MRPC telescope, installed in the Liceo Scientifico “B.Touschek” in Grottaferrata near the LNF-INFN site (nearby Rome), is successfully running. By the end of year 2007, the installation of the other telescopes will open the way for the first search of high-energy cosmic rays distant coincidences. In the future, serving many High Schools scattered all over the Italian territory, the EEE Project will also allow to investigate coincidences between multiple primaries producing distant showers. Here we present the experimental apparatus and its tasks.

  12. ILC Vertex Tracker R&D

    SciTech Connect

    Battaglia, Marco; Bussat, Jean-Marie; Contarato, Devis; Denes,Peter; Glesener, Lindsay; Greiner, Leo; Hooberman, Benjamin; Shuman,Derek; Tompkins, Lauren; Vu, Chinh; Bisello, Dario; Giubilato, Piero; Pantano, Devis; Costa, Marco; La Rosa, Alessandro; Bolla, Gino; Bortoletto, Daniela; Children, Isaac

    2007-10-01

    This document summarizes past achievements, current activities and future goals of the R&D program aimed at the design, prototyping and characterization of a full detector module, equipped with monolithic pixel sensors, matching the requirements for the Vertex Tracker at the ILC. We provide a plan of activities to obtain a demonstrator multi-layered vertex tracker equipped with sensors matching the ILC requirements and realistic lightweight ladders in FY11, under the assumption that ILC detector proto-collaborations will be choosing technologies and designs for the Vertex Tracker by that time. The R&D program discussed here started at LBNL in 2004, supported by a Laboratory Directed R&D (LDRD) grant and by funding allocated from the core budget of the LBNL Physics Division and from the Department of Physics at UC Berkeley. Subsequently additional funding has been awarded under the NSF-DOE LCRD program and also personnel have become available through collaborative research with other groups. The aim of the R&D program carried out by our collaboration is to provide a well-integrated, inclusive research effort starting from physics requirements for the ILC Vertex Tracker and addressing Si sensor design and characterization, engineered ladder design, module system issues, tracking and vertex performances and beam test validation. The broad scope of this program is made possible by important synergies with existing know-how and concurrent programs both at LBNL and at the other collaborating institutions. In particular, significant overlaps with LHC detector design, SLHC R&D as well as prototyping for the STAR upgrade have been exploited to optimize the cost per deliverable of our program. This activity is carried out as a collaborative effort together with Accelerator and Fusion Research, the Engineering and the Nuclear Science Divisions at LBNL, INFN and the Department of Physics in Padova, Italy, INFN and the Department of Physics in Torino, Italy and the Department

  13. Design of a large acceptance, high efficiency energy selection system for the ELIMAIA beam-line

    NASA Astrophysics Data System (ADS)

    Schillaci, F.; Maggiore, M.; Andó, L.; Cirrone, G. A. P.; Cuttone, G.; Romano, F.; Scuderi, V.; Allegra, L.; Amato, A.; Gallo, G.; Korn, G.; Leanza, R.; Margarone, D.; Milluzzo, G.; Petringa, G.

    2016-08-01

    A magnetic chicane based on four electromagnetic dipoles is going to be realized by INFN-LNS to be used as an Energy Selection System (ESS) for laser driven proton beams up to 300 MeV and C6+ up to 70 MeV/u. The system will provide, as output, ion beams with a contrallable energy spread varying from 5% up to 20% according to the aperture slit size. Moreover, it has a very wide acceptance in order to ensure a very high transmission efficiency and, in principle, it has been designed to be used also as an active energy modulator. This system is the core element of the ELIMED (ELI-Beamlines MEDical and Multidisciplinary applications) beam transport, dosimetry and irradiation line that will be developed by INFN-LNS (It) and installed at the ELI-Beamlines facility in Prague (Cz). ELIMED will be the first user's open transport beam-line where a controlled laser-driven ion beam will be used for multidisciplinary research. The definition of well specified characteristics, both in terms of performance and field quality, of the magnetic chicane is crucial for the system realization, for the accurate study of the beam dynamics and for the proper matching with the Permanent Magnet Quadrupoles (PMQs) used as a collection system already designed. Here, the design of the magnetic chicane is described in details together with the adopted solutions in order to realize a robust system form the magnetic point of view. Moreover, the first preliminary transport simulations are also described showing the good performance of the whole beam line (PMQs+ESS).

  14. ELIMED, future hadrontherapy applications of laser-accelerated beams

    NASA Astrophysics Data System (ADS)

    Cirrone, Giuseppe A. P.; Carpinelli, Massimo; Cuttone, Giacomo; Gammino, Santo; Bijan Jia, S.; Korn, Georg; Maggiore, Mario; Manti, Lorenzo; Margarone, Daniele; Prokupek, Jan; Renis, Marcella; Romano, Francesco; Schillaci, Francesco; Tomasello, Barbara; Torrisi, Lorenzo; Tramontana, Antonella; Velyhan, Andriy

    2013-12-01

    Laser-ion acceleration has recently gained a great interest as an alternative to conventional and more expensive acceleration techniques. These ion beams have desirable qualities such as small source size, high luminosity and small emittance to be used in different fields as Nuclear Physics, Medical Physics, etc. This is very promising specially for the future perspective of a new concept of hadrontherapy based on laser-based devices could be developed, replacing traditional accelerating machines. Before delivering laser-driven beams for treatments they have to be handled, cleaned from unwanted particles and characterized in order to have the clinical requirements. In fact ion energy spectra have exponential trend, almost 100% energy spread and a wide angular divergence which is the biggest issue in the beam transport and, hence, in a wider use of this technology. In order to demonstrate the clinical applicability of laser-driven beams new collaboration between ELI-Beamlines project researchers from Prague (Cz) and a INFN-LNS group from Catania (I) has been already launched and scientists from different countries have already express their will in joining the project. This cooperation has been named ELIMED (MEDical application at ELIBeamlines) and will take place inside the ELI-Beamlines infrastructure located in Prague. This work describes the schedule of the ELIMED project and the design of the energy selector which will be realized at INFN-LNS. The device is an important part of the whole transport beam line which will be realised in order to make the ion beams suitable for medical applications.

  15. Theoretical Virtual Observatory and Grid Web services: VisIVO and new capabilities

    NASA Astrophysics Data System (ADS)

    Costa, A.; Becciani, U.; Gheller, C.; Comparato, M.; Larsson, B.

    2007-08-01

    VisIVO is a tool for 3D visualization, it provides an effective and intuitive way of managing, visualizing and analysing the large amount of data produced by observations and numerical simulations. The software is specifically designed to deal with multidimensional data. Catalogues and numerical simulations represent the basic target of VisIVO. The package is written in C++. This poster describes VIsIVO's Grid Web Service (VWS) and its counterpart client side developed in VisIVO. VisIVO's Grid Web Service is developed as a part of the Italian Virtual Observatory, it allows to run applications in grid using the web service technology. The VWS has been designed to work within a Virtual Observatory environment so that the interface for the current application, shown in this poster, and the interfaces for other applications are described by a small and constant piece of WSDL code. Our first application is HOP: an algorithm for finding groups of particles based on the one developed and coded by Daniel Eisenstein & Piet Hut, Institute for Advanced Study, Princeton, NJ. We have developed VWS using Java AXIS libraries for the server side and C++ AXIS libraries for the client side. The access to the computational resources and storage areas is based on grid services in the INFN Production Grid and from this the VWS inherits asynchronous features, scheduling and matching algorithms. HOP was distributed as RPM Package and was installed in the Worker Node Elements of the INFN Production Grid. The idea is to use external tools through the grid avoiding the integration in our application. We can focus on the I/O management of the jobs and on the standardization of the access methods for the different analysis tools improving the scalability of our solution.

  16. The Science Training Program for Young Italian Physicists and Engineers at Fermilab

    SciTech Connect

    Barzi, Emanuela; Bellettini, Giorgio; Donati, Simone

    2015-03-12

    Since 1984 Fermilab has been hosting a two-month summer training program for selected undergraduate and graduate Italian students in physics and engineering. Building on the traditional close collaboration between the Italian National Institute of Nuclear Physics (INFN) and Fermilab, the program is supported by INFN, by the DOE and by the Scuola Superiore di Sant`Anna of Pisa (SSSA), and is run by the Cultural Association of Italians at Fermilab (CAIF). This year the University of Pisa has qualified it as a “University of Pisa Summer School”, and will grant successful students with European Supplementary Credits. Physics students join the Fermilab HEP research groups, while engineers join the Particle Physics, Accelerator, Technical, and Computing Divisions. Some students have also been sent to other U.S. laboratories and universities for special trainings. The programs cover topics of great interest for science and for social applications in general, like advanced computing, distributed data analysis, nanoelectronics, particle detectors for earth and space experiments, high precision mechanics, applied superconductivity. In the years, over 350 students have been trained and are now employed in the most diverse fields in Italy, Europe, and the U.S. In addition, the existing Laurea Program in Fermilab Technical Division was extended to the whole laboratory, with presently two students in Master’s thesis programs on neutrino physics and detectors in the Neutrino Division. And finally, a joint venture with the Italian Scientists and Scholars North-America Foundation (ISSNAF) provided this year 4 professional engineers free of charge for Fermilab. More details on all of the above can be found below.

  17. High density plasmas and new diagnostics: An overview (invited)

    NASA Astrophysics Data System (ADS)

    Celona, L.; Gammino, S.; Mascali, D.

    2016-02-01

    One of the limiting factors for the full understanding of Electron Cyclotron Resonance Ion Sources (ECRISs) fundamental mechanisms consists of few types of diagnostic tools so far available for such compact machines. Microwave-to-plasma coupling optimisation, new methods of density overboost provided by plasma wave generation, and magnetostatic field tailoring for generating a proper electron energy distribution function, suitable for optimal ion beams formation, require diagnostic tools spanning across the entire electromagnetic spectrum from microwave interferometry to X-ray spectroscopy; these methods are going to be implemented including high resolution and spatially resolved X-ray spectroscopy made by quasi-optical methods (pin-hole cameras). The ion confinement optimisation also requires a complete control of cold electrons displacement, which can be performed by optical emission spectroscopy. Several diagnostic tools have been recently developed at INFN-LNS, including "volume-integrated" X-ray spectroscopy in low energy domain (2-30 keV, by using silicon drift detectors) or high energy regime (>30 keV, by using high purity germanium detectors). For the direct detection of the spatially resolved spectral distribution of X-rays produced by the electronic motion, a "pin-hole camera" has been developed also taking profit from previous experiences in the ECRIS field. The paper will give an overview of INFN-LNS strategy in terms of new microwave-to-plasma coupling schemes and advanced diagnostics supporting the design of new ion sources and for optimizing the performances of the existing ones, with the goal of a microwave-absorption oriented design of future machines.

  18. Next-generation Lunar Laser Retroreflectors for Precision Tests of General Relativity

    NASA Astrophysics Data System (ADS)

    Ciocci, Emanuele; dell'Agnello, Simone; Delle Monache, Giovanni; Martini, Manuele; Contessa, Stefania; Porcelli, Luca; Tibuzzi, Mattia; Salvatori, Lorenzo; Patrizi, Giordano; Maiello, Mauro; Intaglietta, Nicola; Mondaini, Chiara; Currie, Douglas; Chandler, John; Bianco, Giuseppe; Murphy, Tom

    2016-04-01

    Since 1969, Lunar Laser Ranging (LLR) to the Apollo Cube Corner Retroreflectors (CCRs) has supplied almost all significant tests of General Relativity (GR). When first installed in the 1970s, the Apollo CCRs geometry contributed only a negligible fraction of the ranging error budget. Today, because of lunar librations, this contribution dominates the error budget, limiting the precision of the experimental tests of gravitational theories. The new MoonLIGHT-2 (Moon Laser Instrumentation for General relativity High-accuracy Tests) apparatus is a new-generation LLR payload developed by the SCF_Lab (http://www.lnf.infn.it/esperimenti/etrusco/) at INFN-LNF in collaboration with the Maryland University. With the unique design of a single large CCR unaffected by librations, MoonLIGHT-2 can increase up to a factor 100 the precision of the measurement of the lunar geodetic precession and other General Relativity (GR) tests respect to Apollo CCRs. MoonLIGHT-2 is approved to be launched with the Moon Express mission MEX-1 and will be deployed on the Moon surface in 2018. MoonLIGHT-2 is also proposed for the Roscosmos mission Luna-27. To validate/optimize MoonLIGHT-2 for MEX-1, the SCF_Lab is carrying out a unique experimental test called SCF-Test: the concurrent measurement of the optical Far Field Diffraction Pattern (FFDP) and the temperature distribution of the CCR under thermal conditions produced with a close-match solar simulator and simulated space environment. We perform test of GR with current LLR data and also different GR simulation of the expected improvement in GR test provided by MoonLIGHT-2, using the Planetary Ephemeris Program in collaboration with CfA. Our ultimate goal is to improve GR tests by a factor up to 100, and provide constraints on the new gravitational theories like non-miminally coupled gravity and spacetime torision.

  19. PREFACE Preface

    NASA Astrophysics Data System (ADS)

    Bleicher, Markus; Caines, Helen; Calderon de la Barca Sanchez, Manuel; de Falco, Alessandro; Fries, Rainer; Granier de Cassagnac, Raphael; Hippolyte, Boris; Mischke, Andre; Nardi, Marzia; Salgado, Carlos A.

    2011-01-01

    The 4th Workshop for Young Scientists on the Physics of Ultrarelativistic Nucleus-nucleus Collisions (Hot Quarks 2010) was held in La Londe-Les-Maures, France, from June 21-26, 2010. Following the traditions of the conference, this meeting gathered more than 70 participants in the first years of their scientific careers. The present issue contains the proceedings of this workshop. The articles published in this volume clearly show the presence of a dynamic new generation of physicists interested in the different aspects of high energy nuclear collisions. The newest results from RHIC at Brookhaven and SPS at CERN were presented, as well as the latest results from the proton-proton programme from the LHC at CERN, while waiting for the data of the lead-lead collisions only available some months after the meeting. Along with these experimental findings, the corresponding theoretical research was also extensively discussed as well as the new perspectives for future facilities like FAIR, EIC and LHeC. We wish to thank the sponsors of the Hot Quarks 2010 Conference, who supported the authors of this volume: IN2P3/CNRS (France), EMMI (Germany), Institut Pluridisciplinaire Hubert Curien (France), National Science Foundation (USA), CERN (Switzerland), Helmholtz International Center for FAIR (Germany), Xunta de Galicia (Spain) and the Journal of Physics G. Markus Bleicher (Frankfurt (HIC4FAIR), Germany)Helen Caines (Yale University, USA)Manuel Calderon de la Barca Sanchez (UC Davis, USA)Alessandro de Falco (Cagliari/INFN, Italy)Rainer Fries (Texas A & M University, USA) Raphael Granier de Cassagnac (Ecole Polytechnique, France)Boris Hippolyte (IPHC, Strasbourg, France)Andre Mischke (Utrecht University, The Netherlands)Marzia Nardi (Torino/INFN, Italy)Carlos A Salgado (Universidade de Santiago de Compostela, Galicia, Spain)

  20. GPCALMA: implementation in Italian hospitals of a computer aided detection system for breast lesions by mammography examination.

    PubMed

    Lauria, Adele

    2009-06-01

    We describe the implementation in several Italian hospitals of a computer aided detection (CAD) system, named GPCALMA (grid platform for a computer aided library in mammography), for the automatic search of lesions in X-ray mammographies. GPCALMA has been under development since 1999 by a community of physicists of the Italian National Institute for Nuclear Physics (INFN) in collaboration with radiologists. This CAD system was tested as a support to radiologists in reading mammographies. The main system components are: (i) the algorithms implemented for the analysis of digitized mammograms to recognize suspicious lesions, (ii) the database of digitized mammographic images, and (iii) the PC-based digitization and analysis workstation and its user interface. The distributed nature of data and resources and the prevalence of geographically remote users suggested the development of the system as a grid application: the design of this networked version is also reported. The paper describes the system architecture, the database of digitized mammographies, the clinical workstation and the medical applications carried out to characterize the system. A commercial CAD was evaluated in a comparison with GPCALMA by analysing the medical reports obtained with and without the two different CADs on the same dataset of images: with both CAD a statistically significant increase in sensitivity was obtained. The sensitivity in the detection of lesions obtained for microcalcification and masses was 96% and 80%, respectively. An analysis in terms of receiver operating characteristic (ROC) curve was performed for massive lesion searches, achieving an area under the ROC curve of A(z)=0.783+/-0.008. Results show that the GPCALMA CAD is ready to be used in the radiological practice, both for screening mammography and clinical studies. GPCALMA is a starting point for the development of other medical imaging applications such as the CAD for the search of pulmonary nodules, currently under

  1. Preliminary timing measurements on a data acquisition chain for a SiPM-based detector for prostate imaging

    NASA Astrophysics Data System (ADS)

    Gabrielli, A.; Antonioli, P.; D'Antone, I.; Giorgi, F. M.; Lax, I.; Lolli, M.; De Leo, R.; De Robertis, G.; Foresta, M.; Loddo, F.; Ranieri, A.; Cosentino, G.; Finocchiaro, P.; Pappalardo, A. D.; Fonte, R.; Calvini, C.; Musico, P.; Ottonello, P.; Cusanno, F.; Garibaldi, F.; Gigli, T.; Giove, F.; Maraviglia, B.; Meddi, F.; Rivetti, A.

    2011-06-01

    Prostate cancer (PC) is one of the most common diseases in western countries and a leading cause of cancer death. A variety of treatment options are available but a precise disease characterization is needed: evaluation of cancer location, size, and extent and an indication of tumor aggressiveness. The current standard for diagnosing PC is transrectal ultrasound guided sextant biopsy. A novel multidisciplinary approach is required. Imaging may play a key role provided that dedicated prostate imagers and procedures are available: considerable improvements have been achieved in diagnosis with the Magnetic Resonance Imaging (MRI) and nuclear medicine (Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT)) techniques. Nevertheless, due to sub-optimal prostate imaging geometries with these generic large instruments preventing separation of the signal from surrounding organs, the sensitivity, spatial resolution and lesion contrast detected are lower compared to what can be potentially achievable with optimized dedicated prostate imagers and procedures. Fully exploiting the Time Of Flight (TOF) capability would allow not only to increase the Signal-to-Noise ratio (SNR) / Noise Equivalent Count Rate (NECR) but also to get rid of the huge background coming from neighboring organs i.e. the bladder. Recently a new research project was initiated by a large INFN collaboration, and a "TOF-PET and MRI for prostate cancer diagnosis and follow up experiment" (TOPEM) was financed as a 3-year experiment by the Italian "INFN Commissione Scientifica Nazionale V" with the goal of designing, building and testing in phantom tests an endorectal PET-TOF probe compatible with MRI.

  2. High density plasmas and new diagnostics: An overview (invited).

    PubMed

    Celona, L; Gammino, S; Mascali, D

    2016-02-01

    One of the limiting factors for the full understanding of Electron Cyclotron Resonance Ion Sources (ECRISs) fundamental mechanisms consists of few types of diagnostic tools so far available for such compact machines. Microwave-to-plasma coupling optimisation, new methods of density overboost provided by plasma wave generation, and magnetostatic field tailoring for generating a proper electron energy distribution function, suitable for optimal ion beams formation, require diagnostic tools spanning across the entire electromagnetic spectrum from microwave interferometry to X-ray spectroscopy; these methods are going to be implemented including high resolution and spatially resolved X-ray spectroscopy made by quasi-optical methods (pin-hole cameras). The ion confinement optimisation also requires a complete control of cold electrons displacement, which can be performed by optical emission spectroscopy. Several diagnostic tools have been recently developed at INFN-LNS, including "volume-integrated" X-ray spectroscopy in low energy domain (2-30 keV, by using silicon drift detectors) or high energy regime (>30 keV, by using high purity germanium detectors). For the direct detection of the spatially resolved spectral distribution of X-rays produced by the electronic motion, a "pin-hole camera" has been developed also taking profit from previous experiences in the ECRIS field. The paper will give an overview of INFN-LNS strategy in terms of new microwave-to-plasma coupling schemes and advanced diagnostics supporting the design of new ion sources and for optimizing the performances of the existing ones, with the goal of a microwave-absorption oriented design of future machines. PMID:26931960

  3. A prototype Infrastructure for Cloud-based distributed services in High Availability over WAN

    NASA Astrophysics Data System (ADS)

    Bulfon, C.; Carlino, G.; De Salvo, A.; Doria, A.; Graziosi, C.; Pardi, S.; Sanchez, A.; Carboni, M.; Bolletta, P.; Puccio, L.; Capone, V.; Merola, L.

    2015-12-01

    In this work we present the architectural and performance studies concerning a prototype of a distributed Tier2 infrastructure for HEP, instantiated between the two Italian sites of INFN-Romal and INFN-Napoli. The network infrastructure is based on a Layer-2 geographical link, provided by the Italian NREN (GARR), directly connecting the two remote LANs of the named sites. By exploiting the possibilities offered by the new distributed file systems, a shared storage area with synchronous copy has been set up. The computing infrastructure, based on an OpenStack facility, is using a set of distributed Hypervisors installed in both sites. The main parameter to be taken into account when managing two remote sites with a single framework is the effect of the latency, due to the distance and the end-to-end service overhead. In order to understand the capabilities and limits of our setup, the impact of latency has been investigated by means of a set of stress tests, including data I/O throughput, metadata access performance evaluation and network occupancy, during the life cycle of a Virtual Machine. A set of resilience tests has also been performed, in order to verify the stability of the system on the event of hardware or software faults. The results of this work show that the reliability and robustness of the chosen architecture are effective enough to build a production system and to provide common services. This prototype can also be extended to multiple sites with small changes of the network topology, thus creating a National Network of Cloud-based distributed services, in HA over WAN.

  4. Profound defects in pancreatic beta-cell function in mice with combined heterozygous mutations in Pdx-1, Hnf-1alpha, and Hnf-3beta.

    PubMed

    Shih, David Q; Heimesaat, Markus; Kuwajima, Satoru; Stein, Roland; Wright, Christopher V E; Stoffel, Markus

    2002-03-19

    Defects in pancreatic beta-cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1alpha, -3beta, -4alpha, and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in beta-cell development and function. In mice, a heterozygous mutation in Pdx-1 alone, but not Hnf-1alpha(+/-), Hnf-3beta(+/-), or Hnf-4alpha(+/-), causes impaired glucose-stimulated insulin secretion in mice. To investigate the possible functional relationships between these transcription factors on beta-cell activity in vivo, we generated mice with the following combined heterozygous mutations: Pdx-1(+/-)/Hnf-1alpha(+/-), Pdx-1(+/-)/Hnf-3beta(+/-), Pdx-1(+/-)/Hnf-4alpha(+/-), Hnf-1alpha(+/-)/Hnf-4alpha(+/-), and Hnf-3beta(+/-)/Hnf-4alpha(+/-). The greatest loss in function was in combined heterozygous null alleles of Pdx-1 and Hnf-1alpha (Pdx-1(+/-)/Hnf-1alpha(+/-)), or Pdx-1 and Hnf-3beta (Pdx-1(+/-)/Hnf-3beta(+/-)). Both double mutants develop progressively impaired glucose tolerance and acquire a compromised first- and second-phase insulin secretion profile in response to glucose compared with Pdx-1(+/-) mice alone. The loss in beta-cell function in Pdx-1(+/-)/Hnf-3beta(+/-) mice was associated with decreased expression of Nkx-6.1, glucokinase (Gck), aldolase B (aldo-B), and insulin, whereas Nkx2.2, Nkx-6.1, Glut-2, Gck, aldo-B, the liver isoform of pyruvate kinase, and insulin expression was reduced in Pdx-1(+/-)/Hnf-1alpha(+/-) mice. The islet cell architecture was also abnormal in Pdx-1(+/-)/Hnf-3beta(+/-) and Pdx-1(+/-)/Hnf-1alpha(+/-) mice, with glucagon-expressing cells scattered throughout the islet, a defect that may be connected to decreased E-cadherin expression. Our data suggest that functional interactions between key islet regulatory factors play an important role in maintaining islet architecture and

  5. Transforming Growth Factor-β-Dependent and -Independent Pathways of Induction of Tubulointerstitial Fibrosis in β6−/− Mice

    PubMed Central

    Ma, Li-Jun; Yang, Haichun; Gaspert, Ariana; Carlesso, Gianluca; Barty, Melissa M.; Davidson, Jeffrey M.; Sheppard, Dean; Fogo, Agnes B.

    2003-01-01

    Transforming growth factor-β1 (TGF-β1) and the renin-angiotensin-aldosterone system are key mediators in kidney fibrosis. Integrin αvβ6, a heterodimeric matrix receptor expressed in epithelia, binds and activates latent TGF-β1. We used β6 integrin-null mice (β6−/−) to determine the role of local TGF-β1 activation in renal fibrosis in the unilateral ureteral obstruction (UUO) model. Obstructed kidneys from β6−/− mice showed less injury than obstructed kidneys from wild-type (WT) mice, associated with lower collagen I, collagen III, plasminogen activator inhibitor (PAI-1), and TGF-β1 mRNA levels and lower collagen content. Infusion with either angiotensin II (Ang II) or aldosterone (Aldo) or combination in β6−/− UUO mice significantly increased collagen contents to levels comparable to those in identically treated WT. Active TGF-β protein expression in β6−/− mice was less in UUO kidneys with or without Ang II infusion compared to matched WT mice. Activated Smad 2 levels in β6−/− obstructed kidneys were lower than in WT UUO mice, and did not increase when fibrosis was induced in β6−/− UUO mice by Ang II infusion. Anti-TGF-β antibody only partially decreased this Ang II-stimulated fibrosis in β6−/− UUO kidneys. In situ hybridization and immunostaining showed low expression of PAI-1 mRNA and protein in tubular epithelium in β6−/− UUO kidneys, with increased PAI-1 expression in response to Ang II, Aldo, or both. Our results indicate that interruption of αvβ6-mediated activation of TGF-β1 can protect against tubulointerstitial fibrosis. Further, the robust induction of tubulointerstitial fibrosis without increase in activated Smad 2 levels in obstructed β6−/− mice by Ang II suggests the existence of a TGF-β1-independent pathway of induction of fibrosis through angiotensin. PMID:14507636

  6. Expressions of ecological identity across the life span of eight environmental exemplars

    NASA Astrophysics Data System (ADS)

    Seydel, Jennifer

    While there is a substantial body of literature looking at various aspects of ecological identity and factors that influence it, there has been less work done on how an individual's ecological identity changes with time. Much of that work is limited to short segments of the life span (e.g. the impact of wilderness experiences). This dissertation attempts to address this perceived gap by investigating how the ecological identity of eight environmental exemplars changed during the course of his or her life. What has emerged from this qualitative grounded theory investigation of the lives and works of Charles Darwin, John Muir, Aldo Leopold, Marjory Stoneman Douglas, Hazel Wolf, Rachel Carson, James Lovelock and E.O. Wilson are five sequential expressions of ecological identity. These 'stages' serve as a framework to explain ecological identity as a developmental process, both fluid and continuous, rather than at) end product. The development of an ecological identity is traced, through the development of five cognitive foundations and their alignment with five emotional foundations that reflect a progression from a sensory interaction and a kinship bond with nature into a deep understanding of the interconnectedness of all aspects of the planet. The findings reveal the evolution of an ecological identity and suggest the importance of looking beyond content knowledge in the nurturing of ecological attitudes, values, and lifestyles.

  7. Development of Saccharomyces cerevisiae reductase YOL151W mutants suitable for chiral alcohol synthesis using an NADH cofactor regeneration system.

    PubMed

    Yoon, Shin Ah; Jung, Jihye; Park, Seongsoon; Kim, Hyung Kwoun

    2013-02-01

    The aldo-keto reductases catalyze reduction reactions using various aliphatic and aromatic aldehydes/ketones. Most reductases require NADPH exclusively as their cofactors. However, NADPH is much more expensive and unstable than NADH. In this study, we attempted to change the five amino acid residues that interact with the 2'-phosphate group of the adenosine ribose of NADPH. These residues were selected based on a docking model of the YOL151W reductase and were substituted with other amino acids to develop NADH-utilizing enzymes. Ten mutants were constructed by site-directed mutagenesis and expressed in Escherichia coli. Among them, four mutants showed higher reductase activities than wild-type when using the NADH cofactor. Analysis of the kinetic parameters for the wild type and mutants indicated that the kcat/Km value of the Asn9Glu mutant toward NADH increased 3-fold. A docking model was used to show that the carboxyl group of Glu 9 of the mutant formed an additional hydrogen bond with the 2'-hydroxyl group of adenosine ribose. The Asn9Glu mutant was able to produce (R)-ethyl-4-chloro-3-hydroxyl butanoate rapidly when using the NADH regeneration system. PMID:23412065

  8. De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses.

    PubMed

    Meena, Seema; Kumar, Sarma R; Venkata Rao, D K; Dwivedi, Varun; Shilpashree, H B; Rastogi, Shubhra; Shasany, Ajit K; Nagegowda, Dinesh A

    2016-01-01

    Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition.

  9. Primary ∆4-3-oxosteroid 5β-reductase deficiency: two cases in China.

    PubMed

    Zhao, Jing; Fang, Ling-Juan; Setchell, Kenneth D R; Chen, Rui; Li, Li-Ting; Wang, Jian-She

    2012-12-21

    Aldo-keto reductase 1D1 (AKR1D1) deficiency, a rare but life-threatening form of bile acid deficiency, has not been previously described in China. Here, we describe the first two primary ∆4-3-oxosteroid 5β-reductase deficiency patients in Mainland China diagnosed by fast atom bombardment-mass spectroscopy of urinary bile acids and confirmed by genetic analysis. A high proportion of atypical 3-oxo-∆4-bile acids in the urine indicated a deficiency in ∆4-3-oxosteroid 5β-reductase. All of the coding exons and adjacent intronic sequence of the AKR1D1 gene were sequenced using peripheral lymphocyte genomic DNA of two patients and one of the patient's parents. One patient exhibited compound heterozygous mutations: c.396C>A and c.722A>T, while the other was heterozygous for the mutation c.797G>A. Based on these mutations, a diagnosis of primary ∆4-3-oxosteroid 5β-reductase deficiency could be confirmed. With ursodeoxycholic acid treatment and fat-soluble vitamin supplements, liver function tests normalized rapidly, and the degree of hepatomegaly was markedly reduced in both patients.

  10. Designing an Effective Environmental Education Program that Meets the Needs of Stakeholders: A Case Study of the High Lonesome Ranch in DeBeque, Colorado

    NASA Astrophysics Data System (ADS)

    Haley, Bethany M.

    A successful environmental education (EE) program is one that supports the mission of the parent organization, meets the needs of its audiences, and is effective at increasing environmental literacy. The High Lonesome Ranch (HLR), a private corporation that operates according to a mixed-use landscape model inspired by Aldo Leopold's land ethic, intends to develop an EE program that will operate within an associated nonprofit organization, the High Lonesome Institute (HLI), to further the mission of promoting a contemporary land ethic. Although HLR owners and staff are motivated to develop an EE program, there is currently no clear consensus regarding an overall vision for the program. The purpose of my thesis is to provide HLR owners and their advisors with a recommended design for the education program based on the missions of the HLR and HLI, sound EE theory, stakeholder feedback, and feasibility within the environment of the HLR. To accomplish this, I reviewed pertinent EE literature, reviewed the models used by existing EE programs, and undertook a two-pronged qualitative case study that gathered feedback from the major stakeholders in the HLR/HLI program. The case study included stakeholder interviews and a one-day facilitated charrette. Although feedback from stakeholders on specific program elements ranged widely, there was widespread support for an EE program at the HLR. From this research, I made a series of recommendations regarding how the HLR/HLI should proceed in development, specific program elements, and next steps in the process.

  11. Involvement of an octose ketoreductase and two acyltransferases in the biosynthesis of paulomycins

    NASA Astrophysics Data System (ADS)

    Li, Jine; Wang, Min; Ding, Yong; Tang, Yue; Zhang, Zhiguo; Chen, Yihua

    2016-02-01

    C-4 hydroxyethyl branched octoses have been observed in polysaccharides of several genera of gram negative bacteria and in various antibiotics produced by gram positive bacteria. The C-4 hydroxyethyl branch was proposed to be converted from C-4 acetyl branch by an uncharacterized ketoreduction step. Paulomycins (PAUs) are glycosylated antibiotics with potent inhibitory activity against gram positive bacteria and are structurally defined by its unique C-4‧ hydroxyethyl branched paulomycose moiety. A novel aldo-keto-reductase, Pau7 was characterized as the enzyme catalyzing the stereospecific ketoreduction of 7‧-keto of PAU E (1) to give the C-4‧ hydroxyethyl branched paulomycose moiety of PAU F (2). An acyltransferase Pau6 further decorates the C-4‧ hydroxyethyl branch of paulomycose moiety of 2 by attaching various fatty acyl chains to 7‧-OH to generate diverse PAUs. In addition, another acyltransferase Pau24 was proposed to be responsible for the 13-O-acetylation of PAUs.

  12. Modernizing Natural History: Berkeley's Museum of Vertebrate Zoology in Transition.

    PubMed

    Sunderland, Mary E

    2013-01-01

    Throughout the twentieth century calls to modernize natural history motivated a range of responses. It was unclear how research in natural history museums would participate in the significant technological and conceptual changes that were occurring in the life sciences. By the 1960s, the Museum of Vertebrate Zoology at the University of California, Berkeley, was among the few university-based natural history museums that were able to maintain their specimen collections and support active research. The MVZ therefore provides a window to the modernization of natural history. This paper concentrates on the directorial transitions that occurred at the MVZ between 1965 and 1971. During this period, the MVZ had four directors: Alden H. Miller (Director 1940-1965), an ornithologist; Aldo Starker Leopold (Acting Director 1965-1966), a conservationist and wildlife biologist; Oliver P. Pearson (Director 1966-1971), a physiologist and mammalogist; and David B. Wake (Director 1971-1998), a morphologist, developmental biologist, and herpetologist. The paper explores how a diversity of overlapping modernization strategies, including hiring new faculty, building infrastructure to study live animals, establishing new kinds of collections, and building modern laboratories combined to maintain collections at the MVZ's core. The paper examines the tensions between the different modernization strategies to inform an analysis of how and why some changes were institutionalized while others were short-lived. By exploring the modernization of collections-based research, this paper emphasizes the importance of collections in the transformation of the life sciences.

  13. Intracrine Androgens Enhance Decidualization and Modulate Expression of Human Endometrial Receptivity Genes.

    PubMed

    Gibson, Douglas A; Simitsidellis, Ioannis; Cousins, Fiona L; Critchley, Hilary O D; Saunders, Philippa T K

    2016-01-01

    The endometrium is a complex, steroid-dependent tissue that undergoes dynamic cyclical remodelling. Transformation of stromal fibroblasts (ESC) into specialised secretory cells (decidualization) is fundamental to the establishment of a receptive endometrial microenvironment which can support and maintain pregnancy. Androgen receptors (AR) are present in ESC; in other tissues local metabolism of ovarian and adrenal-derived androgens regulate AR-dependent gene expression. We hypothesised that altered expression/activity of androgen biosynthetic enzymes would regulate tissue availability of bioactive androgens and the process of decidualization. Primary human ESC were treated in vitro for 1-8 days with progesterone and cAMP (decidualized) in the presence or absence of the AR antagonist flutamide. Time and treatment-dependent changes in genes essential for a) intra-tissue biosynthesis of androgens (5α-reductase/SRD5A1, aldo-keto reductase family 1 member C3/AKR1C3), b) establishment of endometrial decidualization (IGFBP1, prolactin) and c) endometrial receptivity (SPP1, MAOA, EDNRB) were measured. Decidualization of ESC resulted in significant time-dependent changes in expression of AKR1C3 and SRD5A1 and secretion of T/DHT. Addition of flutamide significantly reduced secretion of IGFBP1 and prolactin and altered the expression of endometrial receptivity markers. Intracrine biosynthesis of endometrial androgens during decidualization may play a key role in endometrial receptivity and offer a novel target for fertility treatment. PMID:26817618

  14. Ecological sustainability as the fourth landmark in the development of conservation ethics.

    PubMed

    White, Peter S; Tuttle, Julie P

    2013-10-01

    Aldo Leopold, in "The Land Ethic," made 2 important contributions to conservation ethics: he emphasized the community and ecosystem levels of organization and he explicitly included people as members of the biotic community. Leopold's writings remain eloquent, inspirational, and influential, but the ideas he describes are inherently complex, and ecological science has continued to evolve since "The Land Ethic" was published in 1949. We used 4 sets of quotations from Leopold's essays to develop our commentary on the meaning of and challenges in interpreting his work and to explore the ongoing development of conservation ethics: the "A-B cleavage" (Leopold's description of the contrast between utilitarian value versus a broader definition of value in nature), "land health" and the rightness of human action, the right of all species to continued existence in natural populations "at least in spots," and humans as "plain member[s] and citizen[s]" of the "land-community." We define the broader function of land and land health in "The Land Ethic" as including completeness, dynamic stability, and self-renewal in a way that incorporates the needs of humans and all other species. We argue that the consequences of implementing Leopold's land ethic include multiple conservation goals nested within an overall systems approach and that conservation science must clarify the implications of Leopold's ethic by quantitatively investigating and defining large-scale, system-level ecological sustainability. At this scale, land use will encompass areas ranging from large expanses of wilderness to areas dominated by humans.

  15. Climate Literacy Ambassadors

    NASA Astrophysics Data System (ADS)

    Ackerman, S. A.; Mooney, M. E.

    2011-12-01

    The Climate Literacy Ambassadors program is a collaborative effort to advance climate literacy led by the Cooperative Institute of Meteorological Satellite Studies (CIMSS) at the University of Wisconsin-Madison. With support from NASA, CIMSS is coordinating a three-tiered program to train G6-12 teachers to be Ambassadors of Climate Literacy in their schools and communities. The complete training involves participation at a teacher workshop combined with web-based professional development content around Global and Regional Climate Change. The on-line course utilizes e-learning technology to clarify graphs and concepts from the 2007 Intergovernmental Panel on Climate Change Summary for Policy Makers with content intricately linked to the Climate Literacy: The Essential Principles of Climate Science. Educators who take the course for credit can develop lesson plans or opt for a project of their choosing. This session will showcase select lesson plans and projects, ranging from a district-wide action plan that engaged dozens of teachers to Ambassadors volunteering at the Aldo Leopold Climate Change Nature Center to a teacher who tested a GLOBE Student Climate Research Campaign (SCRC) learning project with plans to participate in the SCRC program. Along with sharing successes from the CIMSS Climate Literacy Ambassadors project, we will share lessons learned related to the challenges of sustaining on-line virtual educator communities.

  16. Utilization of digital differential display to identify differentially expressed genes related to rumen development.

    PubMed

    Kato, Daichi; Suzuki, Yutaka; Haga, Satoshi; So, KyoungHa; Yamauchi, Eri; Nakano, Miwa; Ishizaki, Hiroshi; Choi, Kichoon; Katoh, Kazuo; Roh, Sang-Gun

    2016-04-01

    This study aimed to identify the genes associated with the development of the rumen epithelium by screening for candidate genes by digital differential display (DDD) in silico. Using DDD in NCBI's UniGene database, expressed sequence tag (EST)-based gene expression profiles were analyzed in rumen, reticulum, omasum, abomasum and other tissues in cattle. One hundred and ten candidate genes with high expression in the rumen were derived from a library of all tissues. The expression levels of 11 genes in all candidate genes were analyzed in the rumen, reticulum, omasum and abomasum of nine Japanese Black male calves (5-week-old pre-weaning: n = 3; 15-week-old weaned calves: n = 6). Among the 11 genes, only 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), aldo-keto reductase family 1, member C1-like (AKR1C1), and fatty acid binding protein 3 (FABP3) showed significant changes in the levels of gene expression in the rumen between the pre- and post-weaning of calves. These results indicate that DDD analysis in silico can be useful for screening candidate genes related to rumen development, and that the changes in expression levels of three genes in the rumen may have been caused by weaning, aging or both.

  17. Scientists are From Venus, Journalists are From Mars: Bridging the Two Worlds

    NASA Astrophysics Data System (ADS)

    Baron, N.

    2006-12-01

    Media coverage of issues ranging from climate change to evolution often shapes public awareness and opinions about these topics and the science behind them. While scientists can play a critical social role as a resource for journalists and as a valuable information source for the public, they are often frustrated with how their work is portrayed in the press or choose to avoid public discussions completely. In order for science-based policy measures to succeed, scientists must engage in these public discussions and learn how to communicate more effectively - not only with each other, but also with the media, the public, and policy makers. This requires being able to put themselves in the shoes of their audiences. This presentation will provide insights into the world of journalism and offer practical steps that scientists can take to ensure that their research will register on the public's radar screen. Presenter Nancy Baron, Lead Communications Trainer for the Aldo Leopold Program (ALLP) and Ocean Science Outreach Director for COMPASS works closely with leading scientists to help them communicate the contents and importance of their work more effectively and make their science "news" without compromising scientific integrity or credibility.

  18. Lessons from the Trenches

    NASA Astrophysics Data System (ADS)

    Lubchenco, J.

    2006-12-01

    One of the most important roles of science is to inform the discussions and decisions of individuals and institutions. In a world that is changing rapidly, information is urgently needed to help citizens and leaders understand what's happening, what's causing changes, what the implications are and what are the likely consequences of various options. Most everyone agrees that decisions should be informed (not dictated) by scientific information, but achieving that goal has proven a challenge. Decision-makers need to have access to scientific information that is understandable, relevant, useable, current and credible. However, the science is complex, nuanced and difficult to communicate simply. Most scientists are ill equipped to speak in language that is non-technical. Many academic scientists are wary of talking to the press. Academia does not generally reward time spent doing outreach. As a consequence, others step into the breach and communicate their version of `the science.' All too often this means that vested interests spin, distort or cherry-pick information. The result is that decisions are made without good scientific knowledge and science is seen increasingly as a weapon, not as useful knowledge. The presentation will focus on how one program, the Aldo Leopold Leadership Program is training academic environmental scientists to be better communicators of their science to non-scientists. Lessons learned and suggestions for revolutionizing the communication of scientific information will be offered.

  19. Phenology Across the LTER Network: Initial Findings, Future Directions

    NASA Astrophysics Data System (ADS)

    Henebry, G. M.

    2007-12-01

    Phenology is, in the words of Aldo Leopold, a "horizontal science" that cuts across and binds together multiple biological disciplines. It is a far-reaching but poorly understood aspect of the environmental sciences. Phenological research has been a component of the Long Term Ecological Research (LTER) Network at several sites over the years. However, it has not received the attention or resources to bring it to the forefront as an effective theme for interdisciplinary and cross-site synthesis. With the recent establishment of the USA National Phenology Network (USA-NPN), it is appropriate to assess the status of phenological knowledge across the LTER Network. A workshop funded by the LTER Network Office took place at the Sevilleta Field Station during February 26 to March 2, 2007. From the workshop three main products emerged: (1) an inventory of LTER phenology datasets, (2) establishment of a website to facilitate information interchange, and (3) a white paper recommending next steps for the LTER Network to engage the USA-NPN. This poster relates the findings and recommendations of the workshop, including a summary of phenologically explicit and phenologically implicit LTER datasets and illustrations of how the climatic envelopes described by simple weather variables can provide context for phenological comparisons within and across sites.

  20. Induction of a Unique Isoform of the NCOA7 Oxidation Resistance Gene by Interferon β-1b

    PubMed Central

    Yu, Lijian; Croze, Ed; Yamaguchi, Ken D.; Tran, Tiffany; Reder, Anthony T.; Litvak, Vladimir

    2015-01-01

    We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress. PMID:25330068

  1. Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon β-1b.

    PubMed

    Yu, Lijian; Croze, Ed; Yamaguchi, Ken D; Tran, Tiffany; Reder, Anthony T; Litvak, Vladimir; Volkert, Michael R

    2015-03-01

    We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress. PMID:25330068

  2. Promiscuity and diversity in 3-ketosteroid reductases

    PubMed Central

    Penning, Trevor M.; Chen, Mo; Jin, Yi

    2014-01-01

    Many steroid hormones contain a Δ4-3-ketosteroid functionality that undergoes sequential reduction by 5α- or 5β- steroid reductases to produce 5α- or 5β-dihydrosteroids; and a subsequent 3-keto-reduction to produce a series of isomeric tetrahydrosteroids. Apart from steroid 5α-reductase all the remaining enzymes involved in the two step reduction process in humans belong to the aldo-keto reductase (AKR) superfamily. The enzymes involved in 3-ketosteroid reduction are AKR1C1–AKR1C4. These enzymes are promiscuous and also catalyze 20-keto- and 17-keto-steroid reduction. Interest in these reactions exist since they regulate steroid hormone metabolism in the liver, and in steroid target tissues, they may regulate steroid hormone receptor occupancy. In addition many of the dihydrosteroids are not biologically inert. The same enzymes are also involved in the metabolism of synthetic steroids e.g., hormone replacement therapeutics, contraceptive agents and inhaled glucocorticoids, and may regulate drug efficacy at their cognate receptors. This article reviews these reactions and the structural basis for substrate diversity in AKR1C1–AKR1C4, ketosteroid reductases. This article is part of a Special Issue entitled ‘Steroid/Sterol signaling’. PMID:25500069

  3. 36th International Conference on High Energy Physics

    NASA Astrophysics Data System (ADS)

    The Australian particle physics community was honoured to host the 36th ICHEP conference in 2012 in Melbourne. This conference has long been the reference event for our international community. The announcement of the discovery of the Higgs boson at the LHC was a major highlight, with huge international press coverage. ICHEP2012 was described by CERN Director-General, Professor Rolf Heuer, as a landmark conference for our field. In additional to the Higgs announcement, important results from neutrino physics, from flavour physics, and from physics beyond the standard model also provided great interest. There were also updates on key accelerator developments such as the new B-factories, plans for the LHC upgrade, neutrino facilities and associated detector developments. ICHEP2012 exceeded the promise expected of the key conference for our field, and really did provide a reference point for the future. Many thanks to the contribution reviewers: Andy Bakich, Csaba Balazs, Nicole Bell, Catherine Buchanan, Will Crump, Cameron Cuthbert, Ben Farmer, Sudhir Gupta, Elliot Hutchison, Paul Jackson, Geng-Yuan Jeng, Archil Kobakhidze, Doyoun Kim, Tong Li, Antonio Limosani (Head Editor), Kristian McDonald, Nikhul Patel, Aldo Saavedra, Mark Scarcella, Geoff Taylor, Ian Watson, Graham White, Tony Williams and Bruce Yabsley.

  4. Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls

    PubMed Central

    Singh, Mahavir; Kapoor, Aniruddh; Bhatnagar, Aruni

    2015-01-01

    Extensive research has shown that increased production of reactive oxygen species (ROS) results in tissue injury under a variety of pathological conditions and chronic degenerative diseases. While ROS are highly reactive and can incite significant injury, polyunsaturated lipids in membranes and lipoproteins are their main targets. ROS-triggered lipid peroxidation reactions generate a range of reactive carbonyl species (RCS), and these RCS spread and amplify ROS-related injury. Several RCS generated in oxidizing lipids, such as 4-hydroxy trans-2-nonenal (HNE), 4-oxo-2-(E)-nonenal (ONE), acrolein, malondialdehyde (MDA) and phospholipid aldehydes have been shown to be produced under conditions of oxidative stress and contribute to tissue injury and dysfunction by depleting glutathione and other reductants leading to the modification of proteins, lipids, and DNA. To prevent tissue injury, these RCS are metabolized by several oxidoreductases, including members of the aldo-keto reductase (AKR) superfamily, aldehyde dehydrogenases (ALDHs), and alcohol dehydrogenases (ADHs). Metabolism via these enzymes results in RCS inactivation and detoxification, although under some conditions, it can also lead to the generation of signaling molecules that trigger adaptive responses. Metabolic transformation and detoxification of RCS by oxidoreductases prevent indiscriminate ROS toxicity, while at the same time, preserving ROS signaling. A better understanding of RCS metabolism by oxidoreductases could lead to the development of novel therapeutic interventions to decrease oxidative injury in several disease states and to enhance resistance to ROS-induced toxicity. PMID:25559856

  5. Induction of a unique isoform of the NCOA7 oxidation resistance gene by interferon β-1b.

    PubMed

    Yu, Lijian; Croze, Ed; Yamaguchi, Ken D; Tran, Tiffany; Reder, Anthony T; Litvak, Vladimir; Volkert, Michael R

    2015-03-01

    We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.

  6. In search of "the white area": some notes on art in clinical space.

    PubMed

    Molad, Gershon J

    2004-03-01

    Would you consider looking at two paintings instead of reading a more ritualized abstract? In the first painting, the poet W. B. Yeats shows passages from his autobiography to his friend, the poet and painter George Russell. Russell is appalled to read that there is hardly a single fact accurate: "If you show me the manuscript," he tells Yeats, "I will correct the facts." Yeats airily dismisses the offer: "Oh, I do not want accuracy. I only want a picturesque sentence" (Kiberd, 2003). The second painting is an image I cherish in my mind for years: a photo of the Teatro del Mondo (the theater of the world) created by Aldo Rossi, the late Italian architect, for the 1979 Venice Biennale. Built in the Venice tradition of floating theaters, Rossi created a theater on water, a raft tugged by a boat. Within the panoramic view of Venice, there is a "huge piece of carpentry," which looks like a stageset of a child's dream memory: some big connected play-cubes made of light brown wood on a metal grid of scaffolding, and a blue pointed tower. For Rossi, this theater goes beyond the context of Venice. It is like "the Marine buildings in Maine, the wonderful tall light houses--'the houses of the light'--that observe and are observed...[in a] Venetian method of construction...that seeks fantasy only in the real" (Rossi, 1979). PMID:14993843

  7. Human hydroxysteroid dehydrogenases and pre-receptor regulation: insights into inhibitor design and evaluation.

    PubMed

    Penning, Trevor M

    2011-05-01

    Hydroxysteroid dehydrogenases (HSDs) represent a major class of NAD(P)(H) dependent steroid hormone oxidoreductases involved in the pre-receptor regulation of hormone action. This is achieved by HSDs working in pairs so that they can interconvert ketosteroids with hydroxysteroids resulting in a change in ligand potency for nuclear receptors. HSDs belong to two protein superfamilies the aldo-keto reductases and the short-chain dehydrogenase/reductases. In humans, many of the important enzymes have been thoroughly characterized including the elucidation of their three-dimensional structures. Because these enzymes play fundamental roles in steroid hormone action they can be considered to be drug targets for a variety of steroid driven diseases, e.g. metabolic syndrome and obesity, inflammation, and hormone dependent malignancies of the endometrium, prostate and breast. This article will review how fundamental knowledge of these enzymes can be exploited in the development of isoform specific HSD inhibitors from both protein superfamilies. Article from the Special issue on Targeted Inhibitors.

  8. AKR1C3 as a target in castrate resistant prostate cancer.

    PubMed

    Adeniji, Adegoke O; Chen, Mo; Penning, Trevor M

    2013-09-01

    Aberrant androgen receptor (AR) activation is the major driver of castrate resistant prostate cancer (CRPC). CRPC is ultimately fatal and more therapeutic agents are needed to treat this disease. Compounds that target the androgen axis by inhibiting androgen biosynthesis and or AR signaling are potential candidates for use in CRPC treatment and are currently being pursued aggressively. Aldo-keto reductase 1C3 (AKR1C3) plays a pivotal role in androgen biosynthesis within the prostate. It catalyzes the 17-ketoreduction of weak androgen precursors to give testosterone and 5α-dihydrotestosterone. AKR1C3 expression and activity has been implicated in the development of CRPC, making it a rational target. Selective inhibition of AKR1C3 will be important, however, due to the presence of closely related isoforms, AKR1C1 and AKR1C2 that are also involved in androgen inactivation. We examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors. This article is part of a Special Issue entitled 'CSR 2013'.

  9. Promiscuity and diversity in 3-ketosteroid reductases.

    PubMed

    Penning, Trevor M; Chen, Mo; Jin, Yi

    2015-07-01

    Many steroid hormones contain a Δ(4)-3-ketosteroid functionality that undergoes sequential reduction by 5α- or 5β- steroid reductases to produce 5α- or 5β-dihydrosteroids; and a subsequent 3-keto-reduction to produce a series of isomeric tetrahydrosteroids. Apart from steroid 5α-reductase all the remaining enzymes involved in the two step reduction process in humans belong to the aldo-keto reductase (AKR) superfamily. The enzymes involved in 3-ketosteroid reduction are AKR1C1-AKR1C4. These enzymes are promiscuous and also catalyze 20-keto- and 17-keto-steroid reduction. Interest in these reactions exist since they regulate steroid hormone metabolism in the liver, and in steroid target tissues, they may regulate steroid hormone receptor occupancy. In addition many of the dihydrosteroids are not biologically inert. The same enzymes are also involved in the metabolism of synthetic steroids e.g., hormone replacement therapeutics, contraceptive agents and inhaled glucocorticoids, and may regulate drug efficacy at their cognate receptors. This article reviews these reactions and the structural basis for substrate diversity in AKR1C1-AKR1C4, ketosteroid reductases. This article is part of a Special Issue entitled 'Steroid/Sterol signaling'.

  10. 5β-Reduced steroids and human Δ(4)-3-ketosteroid 5β-reductase (AKR1D1).

    PubMed

    Chen, Mo; Penning, Trevor M

    2014-05-01

    5β-Reduced steroids are non-planar steroids that have a 90° bend in their structure to create an A/B cis-ring junction. This novel property is required for bile-acids to act as emulsifiers, but in addition 5β-reduced steroids have remarkable physiology and may act as potent tocolytic agents, endogenous cardiac glycosides, neurosteroids, and can act as ligands for orphan and membrane bound receptors. In humans there is only a single 5β-reductase gene AKR1D1, which encodes Δ(4)-3-ketosteroid-5β-reductase (AKR1D1). This enzyme is a member of the aldo-keto reductase superfamily, but possesses an altered catalytic tetrad, in which Glu120 replaces the conserved His residue. This predominant liver enzyme generates all 5β-dihydrosteroids in the C19-C27 steroid series. Mutations exist in the AKR1D1 gene, which result in loss of protein stability and are causative in bile-acid deficiency.

  11. Ecological sustainability as the fourth landmark in the development of conservation ethics.

    PubMed

    White, Peter S; Tuttle, Julie P

    2013-10-01

    Aldo Leopold, in "The Land Ethic," made 2 important contributions to conservation ethics: he emphasized the community and ecosystem levels of organization and he explicitly included people as members of the biotic community. Leopold's writings remain eloquent, inspirational, and influential, but the ideas he describes are inherently complex, and ecological science has continued to evolve since "The Land Ethic" was published in 1949. We used 4 sets of quotations from Leopold's essays to develop our commentary on the meaning of and challenges in interpreting his work and to explore the ongoing development of conservation ethics: the "A-B cleavage" (Leopold's description of the contrast between utilitarian value versus a broader definition of value in nature), "land health" and the rightness of human action, the right of all species to continued existence in natural populations "at least in spots," and humans as "plain member[s] and citizen[s]" of the "land-community." We define the broader function of land and land health in "The Land Ethic" as including completeness, dynamic stability, and self-renewal in a way that incorporates the needs of humans and all other species. We argue that the consequences of implementing Leopold's land ethic include multiple conservation goals nested within an overall systems approach and that conservation science must clarify the implications of Leopold's ethic by quantitatively investigating and defining large-scale, system-level ecological sustainability. At this scale, land use will encompass areas ranging from large expanses of wilderness to areas dominated by humans. PMID:24033797

  12. Identification and Validation of HCC-specific Gene Transcriptional Signature for Tumor Antigen Discovery.

    PubMed

    Petrizzo, Annacarmen; Caruso, Francesca Pia; Tagliamonte, Maria; Tornesello, Maria Lina; Ceccarelli, Michele; Costa, Valerio; Aprile, Marianna; Esposito, Roberta; Ciliberto, Gennaro; Buonaguro, Franco M; Buonaguro, Luigi

    2016-07-08

    A novel two-step bioinformatics strategy was applied for identification of signatures with therapeutic implications in hepatitis-associated HCC. Transcriptional profiles from HBV- and HCV-associated HCC samples were compared with non-tumor liver controls. Resulting HCC modulated genes were subsequently compared with different non-tumor tissue samples. Two related signatures were identified, namely "HCC-associated" and "HCC-specific". Expression data were validated by RNA-Seq analysis carried out on unrelated HCC samples and protein expression was confirmed according to The Human Protein Atlas" (http://proteinatlas.org/), a public repository of immunohistochemistry data. Among all, aldo-keto reductase family 1 member B10, and IGF2 mRNA-binding protein 3 were found strictly HCC-specific with no expression in 18/20 normal tissues. Target peptides for vaccine design were predicted for both proteins associated with the most prevalent HLA-class I and II alleles. The described novel strategy showed to be feasible for identification of HCC-specific proteins as highly potential target for HCC immunotherapy.

  13. Modulation of cell metabolic pathways and oxidative stress signaling contribute to acquired melphalan resistance in multiple myeloma cells.

    PubMed

    Zub, Kamila Anna; Sousa, Mirta Mittelstedt Leal de; Sarno, Antonio; Sharma, Animesh; Demirovic, Aida; Rao, Shalini; Young, Clifford; Aas, Per Arne; Ericsson, Ida; Sundan, Anders; Jensen, Ole Nørregaard; Slupphaug, Geir

    2015-01-01

    Alkylating agents are widely used chemotherapeutics in the treatment of many cancers, including leukemia, lymphoma, multiple myeloma, sarcoma, lung, breast and ovarian cancer. Melphalan is the most commonly used chemotherapeutic agent against multiple myeloma. However, despite a 70-80% initial response rate, virtually all patients eventually relapse due to the emergence of drug-resistant tumour cells. By using global proteomic and transcriptomic profiling on melphalan sensitive and resistant RPMI8226 cell lines followed by functional assays, we discovered changes in cellular processes and pathways not previously associated with melphalan resistance in multiple myeloma cells, including a metabolic switch conforming to the Warburg effect (aerobic glycolysis), and an elevated oxidative stress response mediated by VEGF/IL8-signaling. In addition, up-regulated aldo-keto reductase levels of the AKR1C family involved in prostaglandin synthesis contribute to the resistant phenotype. Finally, selected metabolic and oxidative stress response enzymes were targeted by inhibitors, several of which displayed a selective cytotoxicity against the melphalan-resistant cells and should be further explored to elucidate their potential to overcome melphalan resistance.

  14. Record-Breaking Early Flowering in the Eastern United States

    PubMed Central

    Ellwood, Elizabeth R.; Temple, Stanley A.; Primack, Richard B.; Davis, Charles C.

    2013-01-01

    Flowering times are well-documented indicators of the ecological effects of climate change and are linked to numerous ecosystem processes and trophic interactions. Dozens of studies have shown that flowering times for many spring-flowering plants have become earlier as a result of recent climate change, but it is uncertain if flowering times will continue to advance as temperatures rise. Here, we used long-term flowering records initiated by Henry David Thoreau in 1852 and Aldo Leopold in 1935 to investigate this question. Our analyses demonstrate that record-breaking spring temperatures in 2010 and 2012 in Massachusetts, USA, and 2012 in Wisconsin, USA, resulted in the earliest flowering times in recorded history for dozens of spring-flowering plants of the eastern United States. These dramatic advances in spring flowering were successfully predicted by historical relationships between flowering and spring temperature spanning up to 161 years of ecological change. These results demonstrate that numerous temperate plant species have yet to show obvious signs of physiological constraints on phenological advancement in the face of climate change. PMID:23342001

  15. Novel oxime-bearing coumarin derivatives act as potent Nrf2/ARE activators in vitro and in mouse model.

    PubMed

    Chang, Ken-Ming; Chen, Huang-Hui; Wang, Tai-Chi; Chen, I-Li; Chen, Yu-Tsen; Yang, Shyh-Chyun; Chen, Yeh-Long; Chang, Hsin-Huei; Huang, Chih-Hsiang; Chang, Jang-Yang; Shih, Chuan; Kuo, Ching-Chuan; Tzeng, Cherng-Chyi

    2015-12-01

    We have designed and synthesized certain novel oxime- and amide-bearing coumarin derivatives as nuclear factor erythroid 2 p45-related factor 2 (Nrf2) activators. The potency of these compounds was measured by antioxidant responsive element (ARE)-driven luciferase activity, level of Nrf2-related cytoprotective genes and proteins, and antioxidant activity. Among them, (Z)-3-(2-(hydroxyimino)-2-phenylethoxy)-2H-chromen-2-one (17a) was the most active, and more potent than the positive t-BHQ in the induction of ARE-driven luciferase activity. Exposure of HSC-3 cells to various concentrations of 17a strongly increased Nrf2 nuclear translocation and the expression level of Nrf2-mediated cytoprotective proteins in a concentration-dependent manner. HSC-3 cells pretreated with 17a significantly reduced t-BOOH-induced oxidative stress. In the animal experiment, Nrf2-mediated cytoprotective proteins, such as aldo-keto reductase 1 subunit C-1 (AKR1C1), glutathione reductase (GR), and heme oxygenase (HO-1), were obviously elevated in the liver of 17a-treated mice than that of control. These results suggested that novel oxime-bearing coumarin 17a is able to activate Nrf2/ARE pathway in vivo and are therefore seen as a promising candidate for further investigation.

  16. Preliminary Statistics from the NASA Alphasat Beacon Receiver in Milan, Italy

    NASA Technical Reports Server (NTRS)

    Nessel, James; Zemba, Michael; Morse, Jacquelynne; Luini, Lorenzo; Riva, Carlo

    2015-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 gigahertz band. NASA GRC has developed and installed a K/Q-band (20/40 gigahertz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20/40 gigahertz signals broadcast from the Alphasat Aldo Paraboni TDP no. 5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we provide an overview of the design and data calibration procedure, and present 6 months of preliminary statistics of the NASA propagation terminal, which has been installed and operating in Milan since May 2014. The Q-band receiver has demonstrated a dynamic range of 40 decibels at an 8-hertz sampling rate. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models.

  17. Preliminary Statistics from the NASA Alphasat Beacon Receiver in Milan, Italy

    NASA Technical Reports Server (NTRS)

    Zemba, Michael J.; Nessel, James A.; Morse, Jacquelynne R.

    2015-01-01

    NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have initiated a joint propagation campaign within the framework of the Alphasat propagation experiment to characterize rain attenuation, scintillation, and gaseous absorption effects of the atmosphere in the 40 GHz band. NASA GRC has developed and installed a KQ-band (20-40 GHz) beacon receiver at the POLIMI campus in Milan, Italy, which receives the 20-40 GHz signals broadcast from the Alphasat Aldo Paraboni TDP5 beacon payload. The primary goal of these measurements is to develop a physical model to improve predictions of communications systems performance within the Q-band. Herein, we provide an overview of the design and data calibration procedure, and present 6 months of preliminary statistics of the NASA propagation terminal, which has been installed and operating in Milan since May 2014. The Q-band receiver has demonstrated a dynamic range of 40 dB at an 8-Hz sampling rate. A weather station with an optical disdrometer is also installed to characterize rain drop size distribution for correlation with physical based models

  18. Comparison of Instantaneous Frequency Scaling from Rain Attenuation and Optical Disdrometer Measurements at K/Q bands

    NASA Technical Reports Server (NTRS)

    Nessel, James; Zemba, Michael; Luini, Lorenzo; Riva, Carlo

    2015-01-01

    Rain attenuation is strongly dependent on the rain rate, but also on the rain drop size distribution (DSD). Typically, models utilize an average drop size distribution, such as those developed by Laws and Parsons, or Marshall and Palmer. However, individual rain events may possess drop size distributions which could be significantly different from the average and will impact, for example, fade mitigation techniques which utilize channel performance estimates from a signal at a different frequency. Therefore, a good understanding of the characteristics and variability of the raindrop size distribution is extremely important in predicting rain attenuation and instantaneous frequency scaling parameters on an event-toevent basis. Since June 2014, NASA Glenn Research Center (GRC) and the Politecnico di Milano (POLIMI) have measured the attenuation due to rain in Milan, Italy, on the 20/40 GHz beacon signal broadcast from the Alphasat TDP#5 Aldo Paraboni Q/V-band Payload. Concomitant with these measurements are the measurements of drop size distribution and rain rate utilizing a Thies Clima laser precipitation monitor (disdrometer). In this paper, we discuss the comparison of the predicted rain attenuation at 20 and 40 GHz derived from the drop size distribution data with the measured rain attenuation. The results are compared on statistical and real-time bases. We will investigate the performance of the rain attenuation model, instantaneous frequency scaling, and the distribution of the scaling factor. Further, seasonal rain characteristics will be analysed.

  19. Structure and Catalytic Mechanism of Human Steroid 5-Reductase (AKR1D1)

    SciTech Connect

    Costanzo, L.; Drury, J; Christianson, D; Penning, T

    2009-01-01

    Human steroid 5{beta}-reductase (aldo-keto reductase (AKR) 1D1) catalyzes reduction of {Delta}{sup 4}-ene double bonds in steroid hormones and bile acid precursors. We have reported the structures of an AKR1D1-NADP{sup +} binary complex, and AKR1D1-NADP{sup +}-cortisone, AKR1D1-NADP{sup +}-progesterone and AKR1D1-NADP{sup +}-testosterone ternary complexes at high resolutions. Recently, structures of AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone complexes showed that the product is bound unproductively. Two quite different mechanisms of steroid double bond reduction have since been proposed. However, site-directed mutagenesis supports only one mechanism. In this mechanism, the 4-pro-R hydride is transferred from the re-face of the nicotinamide ring to C5 of the steroid substrate. E120, a unique substitution in the AKR catalytic tetrad, permits a deeper penetration of the steroid substrate into the active site to promote optimal reactant positioning. It participates with Y58 to create a 'superacidic' oxyanion hole for polarization of the C3 ketone. A role for K87 in the proton relay proposed using the AKR1D1-NADP{sup +}-5{beta}-dihydroprogesterone structure is not supported.

  20. Transcriptomic responses of European flounder (Platichthys flesus) liver to a brominated flame retardant mixture.

    PubMed

    Williams, Tim D; Diab, Amer M; Gubbins, Matt; Collins, Catherine; Matejusova, Iveta; Kerr, Rose; Chipman, James K; Kuiper, Raoul; Vethaak, A Dick; George, Stephen G

    2013-10-15

    Male European flounder (Platichthys flesus) were exposed to a technical mixture of brominated diphenyl ethers (PDBEs, DE-71, Pentamix) that had been purified to remove contaminating dioxins. Controls were exposed to carrier solvent alone. Fish were exposed to decadally increasing concentrations of Pentamix via both sediment and spiked food. The GENIPOL P. flesus cDNA microarray, differentially expressed gene profiling (DEG) and quantitative PCR were employed to detect hepatic transcriptional differences between exposed fish and controls. Gene transcriptional changes were more sensitive to Pentamix exposure than biomarkers measured previously. Pentamix exposure induced transcripts coding for enzymes of xenobiotic metabolism (CYP1A, aldo-keto reductases) and elicited endocrine disruption (vitellogenin and thyroid hormone receptor alpha), with effects on CYP1A and VTG occurring at the highest exposure. Ontology analysis clearly showed dose-responsive changes indicative of oxidative stress, induction of mitochondrial dysfunction, and apoptosis. We conclude that exposure to PBDEs in both sediment and food has a significant adverse effect on a broad range of crucial biochemical processes in the livers of this widely distributed estuarine fish species, the flounder. PMID:23948077

  1. Sulforaphane promotes murine hair growth by accelerating the degradation of dihydrotestosterone.

    PubMed

    Sasaki, Mari; Shinozaki, Shohei; Shimokado, Kentaro

    2016-03-25

    Dihydrotestosterone (DHT) causes the regression of human hair follicles in the parietal scalp, leading to androgenic alopecia (AGA). Sulforaphane (SFN) increases the expression of DHT degrading enzymes, such as 3α-hydroxysteroid dehydrogenases (3α-HSDs), and, therefore, SFN treatment may improve AGA. To determine the effects of SFN on hair growth, we administered SFN (10 mg/kg BW, IP) or vehicle (DMSO) to ob/ob mice for six weeks and examined hair regeneration and the plasma levels of testosterone and DHT. We also tested the effects of SFN on the expression of two forms of 3α-HSD, aldo-keto reductase 1c21 and dehydrogenase/reductase (SDR family) member 9, both in vitro and in vivo. SNF significantly enhanced hair regeneration in ob/ob mice. The mice treated with SFN showed lower plasma levels of testosterone and DHT than those treated with vehicle. SFN increased the mRNA and protein levels of the two forms of 3α-HSD in the liver of the mice and in cultured murine hepatocyte Hepa1c1c7 cells. These results suggest that SFN treatment increases the amount of 3α-HSDs in the liver, accelerates the degradation of blood DHT, and subsequently blocks the suppression of hair growth by DHT. PMID:26923074

  2. Crystal Structures of Quinolinate Synthase in Complex with a Substrate Analogue, the Condensation Intermediate, and Substrate-Derived Product.

    PubMed

    Volbeda, Anne; Darnault, Claudine; Renoux, Oriane; Reichmann, Debora; Amara, Patricia; Ollagnier de Choudens, Sandrine; Fontecilla-Camps, Juan C

    2016-09-14

    The enzyme NadA catalyzes the synthesis of quinolinic acid (QA), the precursor of the universal nicotinamide adenine dinucleotide (NAD) cofactor. Here, we report the crystal structures of complexes between the Thermotoga maritima (Tm) NadA K219R/Y107F variant and (i) the first intermediate (W) resulting from the condensation of dihydroxyacetone phosphate (DHAP) with iminoaspartate and (ii) the DHAP analogue and triose-phosphate isomerase inhibitor phosphoglycolohydroxamate (PGH). In addition, using the TmNadA K219R/Y21F variant, we have reacted substrates and obtained a crystalline complex between this protein and the QA product. We also show that citrate can bind to both TmNadA K219R and its Y21F variant. The W structure indicates that condensation causes dephosphorylation. We propose that catalysis by the K219R/Y107F variant is arrested at the W intermediate because the mutated protein is unable to catalyze its aldo-keto isomerization and/or cyclization that ultimately lead to QA formation. Intriguingly, PGH binds to NadA with its phosphate group at the site where the carboxylate groups of W also bind. Our results shed significant light on the mechanism of the reaction catalyzed by NadA. PMID:27545412

  3. Detoxifying Enzymes at the Cross-Roads of Inflammation, Oxidative Stress, and Drug Hypersensitivity: Role of Glutathione Transferase P1-1 and Aldose Reductase.

    PubMed

    Sánchez-Gómez, Francisco J; Díez-Dacal, Beatriz; García-Martín, Elena; Agúndez, José A G; Pajares, María A; Pérez-Sala, Dolores

    2016-01-01

    Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivity. PMID:27540362

  4. DNA from uncultured organisms as a source of 2,5-diketo-L-gluconic acid reductases.

    SciTech Connect

    Eschenfeldt, W. H.; Stols, L.; Rosenbaum, H.; Khambatta, Z. S.; Quaite, E. R.; Wu, S.; Kilgore, D. C.; Trent, J. D.; Donnelly, M. I.; Genencor International; Eastman Chemical Company

    2001-09-01

    Total DNA of a population of uncultured organisms was extracted from soil samples, and by using PCR methods, the genes encoding two different 2,5-diketo-D-gluconic acid reductases (DKGRs) were recovered. Degenerate PCR primers based on published sequence information gave internal gene fragments homologous to known DKGRs. Nested primers specific for the internal fragments were combined with random primers to amplify flanking gene fragments from the environmental DNA, and two hypothetical full-length genes were predicted from the combined sequences. Based on these predictions, specific primers were used to amplify the two complete genes in single PCRs. These genes were cloned and expressed in Escherichia coli. The purified gene products catalyzed the reduction of 2,5-diketo-D-gluconic acid to 2-keto-L-gulonic acid. Compared to previously described DKGRs isolated from Corynebacterium spp., these environmental reductases possessed some valuable properties. Both exhibited greater than 20-fold-higher k{sub cat}/K{sub m} values than those previously determined, primarily as a result of better binding of substrate. The K{sub m} values for the two new reductases were 57 and 67 {mu}M, versus 2 and 13 mM for the Corynebacterium enzymes. Both environmental DKGRs accepted NADH as well as NADPH as a cosubstrate; other DKGRs and most related aldo-keto reductases use only NADPH. In addition, one of the new reductases was more thermostable than known DKGRs.

  5. De Novo Sequencing and Analysis of Lemongrass Transcriptome Provide First Insights into the Essential Oil Biosynthesis of Aromatic Grasses.

    PubMed

    Meena, Seema; Kumar, Sarma R; Venkata Rao, D K; Dwivedi, Varun; Shilpashree, H B; Rastogi, Shubhra; Shasany, Ajit K; Nagegowda, Dinesh A

    2016-01-01

    Aromatic grasses of the genus Cymbopogon (Poaceae family) represent unique group of plants that produce diverse composition of monoterpene rich essential oils, which have great value in flavor, fragrance, cosmetic, and aromatherapy industries. Despite the commercial importance of these natural aromatic oils, their biosynthesis at the molecular level remains unexplored. As the first step toward understanding the essential oil biosynthesis, we performed de novo transcriptome assembly and analysis of C. flexuosus (lemongrass) by employing Illumina sequencing. Mining of transcriptome data and subsequent phylogenetic analysis led to identification of terpene synthases, pyrophosphatases, alcohol dehydrogenases, aldo-keto reductases, carotenoid cleavage dioxygenases, alcohol acetyltransferases, and aldehyde dehydrogenases, which are potentially involved in essential oil biosynthesis. Comparative essential oil profiling and mRNA expression analysis in three Cymbopogon species (C. flexuosus, aldehyde type; C. martinii, alcohol type; and C. winterianus, intermediate type) with varying essential oil composition indicated the involvement of identified candidate genes in the formation of alcohols, aldehydes, and acetates. Molecular modeling and docking further supported the role of identified protein sequences in aroma formation in Cymbopogon. Also, simple sequence repeats were found in the transcriptome with many linked to terpene pathway genes including the genes potentially involved in aroma biosynthesis. This work provides the first insights into the essential oil biosynthesis of aromatic grasses, and the identified candidate genes and markers can be a great resource for biotechnological and molecular breeding approaches to modulate the essential oil composition. PMID:27516768

  6. Molecular cloning and functional expression of codeinone reductase: the penultimate enzyme in morphine biosynthesis in the opium poppy Papaver somniferum.

    PubMed

    Unterlinner, B; Lenz, R; Kutchan, T M

    1999-06-01

    The narcotic analgesic morphine is the major alkaloid of the opium poppy Papaver somniferum. Its biosynthetic precursor codeine is currently the most widely used and effective antitussive agent. Along the morphine biosynthetic pathway in opium poppy, codeinone reductase catalyzes the NADPH-dependent reduction of codeinone to codeine. In this study, we have isolated and characterized four cDNAs encoding codeinone reductase isoforms and have functionally expressed them in Escherichia coli. Heterologously expressed codeinone reductase-calmodulin-binding peptide fusion protein was purified from E. coli using calmodulin affinity column chromatography in a yield of 10 mg enzyme l-1. These four isoforms demonstrated very similar physical properties and substrate specificity. As least six alleles appear to be present in the poppy genome. A comparison of the translations of the nucleotide sequences indicate that the codeinone reductase isoforms are 53% identical to 6'-deoxychalcone synthase from soybean suggesting an evolutionary although not a functional link between enzymes of phenylpropanoid and alkaloid biosynthesis. By sequence comparison, both codeinone reductase and 6'-deoxy- chalcone synthase belong to the aldo/keto reductase family, a group of structurally and functionally related NADPH-dependent oxidoreductases, and thereby possibly arise from primary metabolism.

  7. Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy.

    PubMed

    Farrow, Scott C; Hagel, Jillian M; Beaudoin, Guillaume A W; Burns, Darcy C; Facchini, Peter J

    2015-09-01

    The gateway to morphine biosynthesis in opium poppy (Papaver somniferum) is the stereochemical inversion of (S)-reticuline since the enzyme yielding the first committed intermediate salutaridine is specific for (R)-reticuline. A fusion between a cytochrome P450 (CYP) and an aldo-keto reductase (AKR) catalyzes the S-to-R epimerization of reticuline via 1,2-dehydroreticuline. The reticuline epimerase (REPI) fusion was detected in opium poppy and in Papaver bracteatum, which accumulates thebaine. In contrast, orthologs encoding independent CYP and AKR enzymes catalyzing the respective synthesis and reduction of 1,2-dehydroreticuline were isolated from Papaver rhoeas, which does not accumulate morphinan alkaloids. An ancestral relationship between these enzymes is supported by a conservation of introns in the gene fusions and independent orthologs. Suppression of REPI transcripts using virus-induced gene silencing in opium poppy reduced levels of (R)-reticuline and morphinan alkaloids and increased the overall abundance of (S)-reticuline and its O-methylated derivatives. Discovery of REPI completes the isolation of genes responsible for known steps of morphine biosynthesis.

  8. Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer

    PubMed Central

    Wang, Zhiqi; Li, Sai; Cao, Yu; Tian, Xuefei; Zeng, Rong; Liao, Duan-Fang; Cao, Deliang

    2016-01-01

    Oxidative stress has long been known as a pathogenic factor of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), but the effects of secondary carbonyl lesions receive less emphasis. In inflammatory conditions, reactive oxygen species (ROS), such as superoxide anion free radical (O2∙−), hydrogen peroxide (H2O2), and hydroxyl radical (HO∙), are produced at high levels and accumulated to cause oxidative stress (OS). In oxidative status, accumulated ROS can cause protein dysfunction and DNA damage, leading to gene mutations and cell death. Accumulated ROS could also act as chemical messengers to activate signaling pathways, such as NF-κB and p38 MAPK, to affect cell proliferation, differentiation, and apoptosis. More importantly, electrophilic carbonyl compounds produced by lipid peroxidation may function as secondary pathogenic factors, causing further protein and membrane lesions. This may in turn exaggerate oxidative stress, forming a vicious cycle. Electrophilic carbonyls could also cause DNA mutations and breaks, driving malignant progression of UC. The secondary lesions caused by carbonyl compounds may be exceptionally important in the case of host carbonyl defensive system deficit, such as aldo-keto reductase 1B10 deficiency. This review article updates the current understanding of oxidative stress and carbonyl lesions in the development and progression of UC and CAC. PMID:26823956

  9. Statil suppresses cancer cell growth and proliferation by the inhibition of tumor marker AKR1B10.

    PubMed

    Cao, Zhe; Zhou, Boping; Chen, Xinchun; Huang, Dan; Zhang, Xiuli; Wang, Ziqi; Huang, Hua; Wang, Yuhong; Cao, Deliang

    2014-09-01

    Aldo-keto reductase 1B10 (AKR1B10) is an oncogenic carbonyl reductase that eliminates α,β-unsaturated carbonyl compounds/lipid peroxides and mediates retinoic acid signaling. Targeted inhibition of AKR1B10 activity is a newly emerging strategy for cancer therapy. This study evaluated the inhibitory activity of a small chemical statil towards AKR1B10 and tested its antiproliferative activity in breast (BT-20) and lung (NCI-H460) cancer cells that express AKR1B10. Experimental results showed that statil inhibited AKR1B10 enzyme activity efficiently, with an IC50 at 0.21±0.06 µmol/l. Exposing BT-20 and NCI-H460 cells to statil and diclofenac, a selective AKR1B10 inhibitor, led to dose-dependent inhibition of cell growth and proliferation and plating efficiency. At higher doses (50 µmol/l or higher), statil induced cell death with apoptotic characteristics, such as DNA fragmentation and Annexin-V staining. Furthermore, statil enhanced the susceptibility of cells to acrolein, an active substrate of AKR1B10. Taken together, these data suggest that statil possesses potent antiproliferative activity by inhibiting AKR1B10 activity.

  10. Involvement of an octose ketoreductase and two acyltransferases in the biosynthesis of paulomycins

    PubMed Central

    Li, Jine; Wang, Min; Ding, Yong; Tang, Yue; Zhang, Zhiguo; Chen, Yihua

    2016-01-01

    C-4 hydroxyethyl branched octoses have been observed in polysaccharides of several genera of gram negative bacteria and in various antibiotics produced by gram positive bacteria. The C-4 hydroxyethyl branch was proposed to be converted from C-4 acetyl branch by an uncharacterized ketoreduction step. Paulomycins (PAUs) are glycosylated antibiotics with potent inhibitory activity against gram positive bacteria and are structurally defined by its unique C-4′ hydroxyethyl branched paulomycose moiety. A novel aldo-keto-reductase, Pau7 was characterized as the enzyme catalyzing the stereospecific ketoreduction of 7′-keto of PAU E (1) to give the C-4′ hydroxyethyl branched paulomycose moiety of PAU F (2). An acyltransferase Pau6 further decorates the C-4′ hydroxyethyl branch of paulomycose moiety of 2 by attaching various fatty acyl chains to 7′-OH to generate diverse PAUs. In addition, another acyltransferase Pau24 was proposed to be responsible for the 13-O-acetylation of PAUs. PMID:26877148

  11. Reductive detoxification of acrolein as a potential role for aldehyde reductase (AKR1A) in mammals.

    PubMed

    Kurahashi, Toshihiro; Kwon, Myoungsu; Homma, Takujiro; Saito, Yuka; Lee, Jaeyong; Takahashi, Motoko; Yamada, Ken-Ichi; Miyata, Satoshi; Fujii, Junichi

    2014-09-12

    Aldehyde reductase (AKR1A), a member of the aldo-keto reductase superfamily, suppresses diabetic complications via a reduction in metabolic intermediates; it also plays a role in ascorbic acid biosynthesis in mice. Because primates cannot synthesize ascorbic acid, a principle role of AKR1A appears to be the reductive detoxification of aldehydes. In this study, we isolated and immortalized mouse embryonic fibroblasts (MEFs) from wild-type (WT) and human Akr1a-transgenic (Tg) mice and used them to investigate the potential roles of AKR1A under culture conditions. Tg MEFs showed higher methylglyoxal- and acrolein-reducing activities than WT MEFs and also were more resistant to cytotoxicity. Enzymatic analyses of purified rat AKR1A showed that the efficiency of the acrolein reduction was about 20% that of glyceraldehyde. Ascorbic acid levels were quite low in the MEFs, and while the administration of ascorbic acid to the cells increased the intracellular levels of ascorbic acid, it had no affect on the resistance to acrolein. Endoplasmic reticulum stress and protein carbonylation induced by acrolein treatment were less evident in Tg MEFs than in WT MEFs. These data collectively indicate that one of the principle roles of AKR1A in primates is the reductive detoxification of aldehydes, notably acrolein, and protection from its detrimental effects.

  12. Landscapes of promise: An examination of students' journals written during a cross-cultural wilderness experience

    NASA Astrophysics Data System (ADS)

    Freund, Judith Ann

    1997-12-01

    This paper is an examination of nature journals written by ten American and ten Russian high school students during a cross-cultural exchange that provided experiences in selected national wilderness areas designated by the respective countries. The students participated in a backpacking excursion in the Lee Metcalf Wilderness Area of Montana in the summer of 1994, and a camping experience in the wilderness areas in the provincial region of Penza, Russia in the summer of 1995. The examination of the journals focuses on the following areas: aesthetic "peak" experiences; spiritual inspiration derived from experiences in nature; attitudes toward the preservation of wildlife; and environmental ethics. The students' attitudes toward the environment is compared using student-identified cultural values of both the Russian and the American students. Also discussed is the viability of the students' reflections as natural history journal-writing, with references to selected natural history authors, including Henry David Thoreau, Aldo Leopold and Anne Dillard. Because the experience focused on wilderness preservation students were invited to speculate about how to develop and reinforce essential attitudes that are respectful of ecology. Conclusions they reached included the necessity to economic security at some level and the notion that direct experience in the environment is essential to developing an attitude that will engender an ethics of caring within their--as well as other--cultural groups.

  13. Identification of a newly isolated erythritol-producing yeast and cloning of its erythrose [corrected] reductase genes.

    PubMed

    Deng, Huihui; Han, Ye; Liu, Yuanyuan; Jia, Wei; Zhou, Zhijiang

    2012-11-01

    A new erythritol-producing yeast (strain BH010) was isolated in this study. Analysis of the D1/D2 domain of the 26S rDNA sequence, the ITS/5.8S rDNA sequence [corrected] and the 18S rDNA sequence allowed the taxonomic position of strain BH010 to be discussed, [corrected] and it was identified and named Moniliella sp. BH010. Physiological characteristics were described. Scanning electron micrography clearly indicated that the cells were cylindrical to elliptical with an average size of 5 × 10 μm when growing in liquid medium [corrected] and that pseudohyphae and blastoconidia were observed when cultivated in agar plates. The erythrose [corrected] reductase genes were cloned, sequenced, and analyzed. BLAST analysis and multiple sequence alignment demonstrated that erythrose [corrected] reductase genes of Moniliella sp. BH010 shared very high homology with that of Trichosporonoides megachiliensis SNG-42 except for the presence of introns. The deduced amino acid sequences showed high homology to the aldo-keto reductase superfamily.

  14. Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis

    PubMed Central

    Cesari, Italo Mario; Figueiredo Rodrigues, Mariana; Mendonça, Bruna dos Santos; Amôedo, Nivea Dias; Rumjanek, Franklin David

    2014-01-01

    Methyl jasmonate (MJ), an oxylipid that induces defense-related mechanisms in plants, has been shown to be active against cancer cells both in vitro and in vivo, without affecting normal cells. Here we review most of the described MJ activities in an attempt to get an integrated view and better understanding of its multifaceted modes of action. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents. PMID:24648844

  15. Thermostable alcohol dehydrogenase from Thermococcus kodakarensis KOD1 for enantioselective bioconversion of aromatic secondary alcohols.

    PubMed

    Wu, Xi; Zhang, Chong; Orita, Izumi; Imanaka, Tadayuki; Fukui, Toshiaki; Xing, Xin-Hui

    2013-04-01

    A novel thermostable alcohol dehydrogenase (ADH) showing activity toward aromatic secondary alcohols was identified from the hyperthermophilic archaeon Thermococcus kodakarensis KOD1 (TkADH). The gene, tk0845, which encodes an aldo-keto reductase, was heterologously expressed in Escherichia coli. The enzyme was found to be a monomer with a molecular mass of 31 kDa. It was highly thermostable with an optimal temperature of 90°C and a half-life of 4.5 h at 95°C. The apparent K(m) values for the cofactors NAD(P)(+) and NADPH were similar within a range of 66 to 127 μM. TkADH preferred secondary alcohols and accepted various ketones and aldehydes as substrates. Interestingly, the enzyme could oxidize 1-phenylethanol and its derivatives having substituents at the meta and para positions with high enantioselectivity, yielding the corresponding (R)-alcohols with optical purities of greater than 99.8% enantiomeric excess (ee). TkADH could also reduce 2,2,2-trifluoroacetophenone to (R)-2,2,2-trifluoro-1-phenylethanol with high enantioselectivity (>99.6% ee). Furthermore, the enzyme showed high resistance to organic solvents and was particularly highly active in the presence of H2O-20% 2-propanol and H2O-50% n-hexane or n-octane. This ADH is expected to be a useful tool for the production of aromatic chiral alcohols.

  16. AKR1C3 as a Target in Castrate Resistant Prostate Cancer

    PubMed Central

    Adeniji, Adegoke O.; Chen, Mo; Penning, Trevor M.

    2013-01-01

    Aberrant androgen receptor (AR) activation is the major driver of castrate resistant prostate cancer (CRPC). CRPC is ultimately fatal and more therapeutic agents are needed to treat this disease. Compounds that target the androgen axis by inhibiting androgen biosynthesis and or AR signaling are potential candidates for use in CRPC treatment and are currently being pursued aggressively. Aldo-keto reductase 1C3 (AKR1C3) plays a pivotal role in androgen biosynthesis within the prostate. It catalyzes the 17-ketoreduction of weak androgen precursors to give testosterone and 5α-dihydrotestosterone. AKR1C3 expression and activity has been implicated in the development of CRPC, making it a rational target. Selective inhibition of AKR1C3 will be important however, due to the presence of closely related isoforms, AKR1C1 and AKR1C2 that are also involved in androgen inactivation. We examine the evidence that supports the vital role of AKR1C3 in CRPC and recent developments in the discovery of potent and selective AKR1C3 inhibitors. PMID:23748150

  17. Embodiment and enculturation: the future of architectural design

    PubMed Central

    Mallgrave, Harry F.

    2015-01-01

    A half-century ago the Dutch architect Aldo van Eyck encouraged designers to think about “space and time” not as abstractions in themselves but rather as cultural events better approached through the medium of “place and occasion.” Van Eyck made this point on the basis of his own travels and through his extensive readings in cultural anthropology, and his prescience is only now acquiring the credibility that it deserves through the work of a multitude of interdisciplinary researchers. Phenomenologists argue that we are embodied organisms-acting-within-environments, and these inhabiting abodes are constructed of both material and cultural dimensions. We are thus preeminently social in our range of self-consciousness, and intensely ceremonial in every facet of our being. Evolutionary psychologists and anthropologists are currently locating the origin and development of our most basic social behaviors far in our pre-human past; neuroscientists are today modeling our social circuits in the deepest reaches of our brains. Architecture would gain much from an updated cultural theory grounded in these new models of human existence. PMID:26441773

  18. Detoxifying Enzymes at the Cross-Roads of Inflammation, Oxidative Stress, and Drug Hypersensitivity: Role of Glutathione Transferase P1-1 and Aldose Reductase

    PubMed Central

    Sánchez-Gómez, Francisco J.; Díez-Dacal, Beatriz; García-Martín, Elena; Agúndez, José A. G.; Pajares, María A.; Pérez-Sala, Dolores

    2016-01-01

    Phase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivity. PMID:27540362

  19. GC/IR computer-aided identification of anaerobic bacteria

    NASA Astrophysics Data System (ADS)

    Ye, Hunian; Zhang, Feng S.; Yang, Hua; Li, Zhu; Ye, Song

    1993-09-01

    A new method was developed to identify anaerobic bacteria by using pattern recognition. The method is depended on GC / JR data. The system is intended for use as a precise rapid and reproduceable aid in the identification of unknown isolates. Key Words: Anaerobic bacteria Pattern recognition Computeraided identification GC / JR 1 . TNTRODUCTTON A major problem in the field of anaerobic bacteriology is the difficulty in accurately precisely and rapidly identifying unknown isolates. Tn the proceedings of the Third International Symposium on Rapid Methods and Automation in Microbiology C. M. Moss said: " Chromatographic analysis is a new future for clinical microbiology" . 12 years past and so far it seems that this is an idea whose time has not get come but it close. Now two major advances that have brought the technology forword in terms ofmaking it appropriate for use in the clinical laboratory can aldo be cited. One is the development and implementation of fused silica capillary columns. In contrast to packed columns and those of'' greater width these columns allow reproducible recovery of hydroxey fatty acids with the same carbon chain length. The second advance is the efficient data processing afforded by modern microcomputer systems. On the other hand the practical steps for sample preparation also are an advance in the clinical laboratory. Chromatographic Analysis means mainly of analysis of fatty acids. The most common

  20. Age-Related Changes in Hepatic Activity and Expression of Detoxification Enzymes in Male Rats

    PubMed Central

    Vyskočilová, Erika; Szotáková, Barbora; Skálová, Lenka; Bártíková, Hana; Hlaváčová, Jitka

    2013-01-01

    Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates. PMID:23971034