Dietary patterns are associated with disease risk among participants in the women's health initiative observational study

USDA-ARS?s Scientific Manuscript database

Coronary heart disease (CHD) is the leading cause of death in women. A nested case-control study tested whether dietary patterns predicted CHD events among 1224 participants in the Women’s Health Initiative-Observational Study (WHI-OS) with centrally confirmed CHD, fatal or nonfatal myocardial infar...

Blueberry diet protect against atherosclerosis in apoE-deficient mice by inhibiting scavenger receptor expression

USDA-ARS?s Scientific Manuscript database

Atherosclerosis is an inflammatory process that leads to the onset of cardiovascular disease. The scavenger receptor-mediated uptake of oxLDL by macrophages leads to foam cell formation, which is an initial event in the formation of atherosclerotic fatty streak lesions. In this report, the mechanism...

Comparative hazard analysis of processes leading to remarkable flash floods (France, 1930-1999)

NASA Astrophysics Data System (ADS)

Boudou, M.; Lang, M.; Vinet, F.; Cœur, D.

2016-10-01

Flash flood events are responsible for large economic losses and lead to fatalities every year in France. This is especially the case in the Mediterranean and oversea territories/departments of France, characterized by extreme hydro-climatological features and with a large part of the population exposed to flood risks. The recurrence of remarkable flash flood events, associated with high hazard intensity, significant damage and socio-political consequences, therefore raises several issues for authorities and risk management policies. This study aims to improve our understanding of the hazard analysis process in the case of four remarkable flood events: March 1930, October 1940, January 1980 and November 1999. Firstly, we present the methodology used to define the remarkability score of a flood event. Then, to identify the factors leading to a remarkable flood event, we explore the main parameters of the hazard analysis process, such as the meteorological triggering conditions, the return period of the rainfall and peak discharge, as well as some additional factors (initial catchment state, flood chronology, cascade effects, etc.). The results contribute to understanding the complexity of the processes leading to flood hazard and highlight the importance for risk managers of taking additional factors into account.

Statistics of initial density perturbations in heavy ion collisions and their fluid dynamic response

NASA Astrophysics Data System (ADS)

Floerchinger, Stefan; Wiedemann, Urs Achim

2014-08-01

An interesting opportunity to determine thermodynamic and transport properties in more detail is to identify generic statistical properties of initial density perturbations. Here we study event-by-event fluctuations in terms of correlation functions for two models that can be solved analytically. The first assumes Gaussian fluctuations around a distribution that is fixed by the collision geometry but leads to non-Gaussian features after averaging over the reaction plane orientation at non-zero impact parameter. In this context, we derive a three-parameter extension of the commonly used Bessel-Gaussian event-by-event distribution of harmonic flow coefficients. Secondly, we study a model of N independent point sources for which connected n-point correlation functions of initial perturbations scale like 1 /N n-1. This scaling is violated for non-central collisions in a way that can be characterized by its impact parameter dependence. We discuss to what extent these are generic properties that can be expected to hold for any model of initial conditions, and how this can improve the fluid dynamical analysis of heavy ion collisions.

Evaluating the atmospheric drivers leading to the December 2014 flood in Schleswig-Holstein, Germany

NASA Astrophysics Data System (ADS)

Schade, Nils H.

2017-06-01

Regional analyses of atmospheric conditions that may cause flooding of important transport infrastructure (railway tracks, highways/roads, rivers/channels) and subsequent adaptation measures are part of topic 1 of the network of experts initiated by the German Federal Ministry of Transport and Digital Infrastructure (BMVI). As an example case study, the December 2014 flood in Schleswig-Holstein, Germany, was investigated. Atmospheric conditions at the onset of the flood event are described and evaluated with respect to the general weather circulation, initial wetness, and event precipitation. Persistent, predominantly westerly general weather circulations (GWCs) directed several low-pressure systems over the North Sea to Schleswig-Holstein during December 2014, accompanied by prolonged rainfall and finally a strong precipitation event in southern Schleswig-Holstein, causing several inland gauges to exceed their, by then maximum, water levels. Results show that the antecedent precipitation index (API) is able to reflect the soil moisture conditions and, in combination with the maximum 3-day precipitation sum (R3d), to capture the two main drivers finally leading to the flood: (1) the initial wetness of north-western Schleswig-Holstein and (2) strong event precipitation in southern and eastern Schleswig-Holstein from 21 to 23 December; at the same time, both indices exceeded their respective 5-year return periods. Further, trend analyses show that both API and R3d have been increasing during recent years, while regional patterns match the north-eastward shift of cyclone pathways, leading to a higher risk of flooding in Schleswig-Holstein. Within the network of experts, investigations of these and further indices/drivers for earth system changes (e.g. wind surge and sea level rise) derived from observations, reanalyses, and regional climate model data are planned for all German coastal areas. Results can be expected to lead to improved adaptation measures to floods under climate change conditions wherever catchments have to be drained and infrastructures and ecosystems may be harmed.

Compelling Evidence of the Need for Corporate Work/Life Balance Initiatives: Results from a National Survey of Stressful Life-Events.

ERIC Educational Resources Information Center

Hobson, Charles J.; Delunas, Linda; Kesic, Dawn

2001-01-01

Considers how failure to balance excessive work and life/family demands can lead to negative consequences for both individuals and organizations, including higher stress levels, increased absenteeism, and lower productivity. Discusses results of a survey on stressful life events that offers an explanation of why work/life balance programs are so…

Measurements of jet charge with dijet events in pp collisions at $$ \\sqrt{s}=8 $$ TeV

DOE PAGES

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; ...

2017-10-19

Here, jet charge is an estimator of the electric charge of a quark, antiquark, or gluon initiating a jet. It is based on the momentum-weighted sum of the electric charges of the jet constituents. Measurements of three charge observables of the leading jet in transverse momentum pT are performed with dijet events. The analysis is carried out with data collected by the CMS experiment at the CERN LHC in proton-proton collisions at √s = 8 TeV corresponding to an integrated luminosity of 19.7fb -1. The results are presented as a function of the pT of the leading jet and comparedmore » to predictions from leading- and next-to-leading-order event generators combined with parton showers. Measured jet charge distributions, unfolded for detector effects, are reported, which expand on previous measurements of the jet charge average and standard deviation in pp collisions.« less

Measurements of jet charge with dijet events in pp collisions at √{s}=8 TeV

NASA Astrophysics Data System (ADS)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Asilar, E.; Bergauer, T.; Brandstetter, J.; Brondolin, E.; Dragicevic, M.; Erö, J.; Flechl, M.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; König, A.; Krätschmer, I.; Liko, D.; Matsushita, T.; Mikulec, I.; Rabady, D.; Rad, N.; Rahbaran, B.; Rohringer, H.; Schieck, J.; Strauss, J.; Waltenberger, W.; Wulz, C.-E.; Dvornikov, O.; Makarenko, V.; Mossolov, V.; Suarez Gonzalez, J.; Zykunov, V.; Shumeiko, N.; Alderweireldt, S.; De Wolf, E. A.; Janssen, X.; Lauwers, J.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Abu Zeid, S.; Blekman, F.; D'Hondt, J.; Daci, N.; De Bruyn, I.; Deroover, K.; Lowette, S.; Moortgat, S.; Moreels, L.; Olbrechts, A.; Python, Q.; Skovpen, K.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Parijs, I.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Luetic, J.; Maerschalk, T.; Marinov, A.; Randle-conde, A.; Seva, T.; Vander Velde, C.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Zenoni, F.; Zhang, F.; Cimmino, A.; Cornelis, T.; Dobur, D.; Fagot, A.; Gul, M.; Khvastunov, I.; Poyraz, D.; Salva, S.; Schöfbeck, R.; Tytgat, M.; Van Driessche, W.; Yazgan, E.; Zaganidis, N.; Bakhshiansohi, H.; Beluffi, C.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; De Visscher, S.; Delaere, C.; Delcourt, M.; Francois, B.; Giammanco, A.; Jafari, A.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Aldá Júnior, W. L.; Alves, F. L.; Alves, G. A.; Brito, L.; Hensel, C.; Moraes, A.; Pol, M. E.; Rebello Teles, P.; Belchior Batista Das Chagas, E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; Da Silveira, G. G.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Huertas Guativa, L. M.; Malbouisson, H.; Matos Figueiredo, D.; Mora Herrera, C.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Torres Da Silva De Araujo, F.; Vilela Pereira, A.; Ahuja, S.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Moon, C. S.; Novaes, S. F.; Padula, Sandra S.; Romero Abad, D.; Ruiz Vargas, J. C.; Aleksandrov, A.; Hadjiiska, R.; Iaydjiev, P.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Litov, L.; Pavlov, B.; Petkov, P.; Fang, W.; Ahmad, M.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Chen, Y.; Cheng, T.; Jiang, C. H.; Leggat, D.; Liu, Z.; Romeo, F.; Ruan, M.; Shaheen, S. M.; Spiezia, A.; Tao, J.; Wang, C.; Wang, Z.; Zhang, H.; Zhao, J.; Ban, Y.; Chen, G.; Li, Q.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Xu, Z.; Avila, C.; Cabrera, A.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; González Hernández, C. F.; Ruiz Alvarez, J. D.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Puljak, I.; Ribeiro Cipriano, P. M.; Sculac, T.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Ferencek, D.; Kadija, K.; Mesic, B.; Susa, T.; Ather, M. W.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Rykaczewski, H.; Finger, M.; Finger, M.; Carrera Jarrin, E.; Assran, Y.; Elkafrawy, T.; Mahrous, A.; Kadastik, M.; Perrini, L.; Raidal, M.; Tiko, A.; Veelken, C.; Eerola, P.; Pekkanen, J.; Voutilainen, M.; Härkönen, J.; Järvinen, T.; Karimäki, V.; Kinnunen, R.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Talvitie, J.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Ghosh, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Kucher, I.; Locci, E.; Machet, M.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Abdulsalam, A.; Antropov, I.; Baffioni, S.; Beaudette, F.; Busson, P.; Cadamuro, L.; Chapon, E.; Charlot, C.; Davignon, O.; Granier de Cassagnac, R.; Jo, M.; Lisniak, S.; Miné, P.; Nguyen, M.; Ochando, C.; Ortona, G.; Paganini, P.; Pigard, P.; Regnard, S.; Salerno, R.; Sirois, Y.; Stahl Leiton, A. G.; Strebler, T.; Yilmaz, Y.; Zabi, A.; Zghiche, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Buttignol, M.; Chabert, E. C.; Chanon, N.; Collard, C.; Conte, E.; Coubez, X.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Bernet, C.; Boudoul, G.; Carrillo Montoya, C. A.; Chierici, R.; Contardo, D.; Courbon, B.; Depasse, P.; El Mamouni, H.; Fay, J.; Gascon, S.; Gouzevitch, M.; Grenier, G.; Ille, B.; Lagarde, F.; Laktineh, I. B.; Lethuillier, M.; Mirabito, L.; Pequegnot, A. L.; Perries, S.; Popov, A.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Khvedelidze, A.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Feld, L.; Kiesel, M. K.; Klein, K.; Lipinski, M.; Preuten, M.; Schomakers, C.; Schulz, J.; Verlage, T.; Albert, A.; Brodski, M.; Dietz-Laursonn, E.; Duchardt, D.; Endres, M.; Erdmann, M.; Erdweg, S.; Esch, T.; Fischer, R.; Güth, A.; Hamer, M.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Knutzen, S.; Merschmeyer, M.; Meyer, A.; Millet, P.; Mukherjee, S.; Olschewski, M.; Padeken, K.; Pook, T.; Radziej, M.; Reithler, H.; Rieger, M.; Scheuch, F.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Cherepanov, V.; Flügge, G.; Kargoll, B.; Kress, T.; Künsken, A.; Lingemann, J.; Müller, T.; Nehrkorn, A.; Nowack, A.; Pistone, C.; Pooth, O.; Stahl, A.; Aldaya Martin, M.; Arndt, T.; Asawatangtrakuldee, C.; Beernaert, K.; Behnke, O.; Behrens, U.; Bin Anuar, A. A.; Borras, K.; Campbell, A.; Connor, P.; Contreras-Campana, C.; Costanza, F.; Diez Pardos, C.; Dolinska, G.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Eren, E.; Gallo, E.; Garay Garcia, J.; Geiser, A.; Gizhko, A.; Grados Luyando, J. M.; Grohsjean, A.; Gunnellini, P.; Harb, A.; Hauk, J.; Hempel, M.; Jung, H.; Kalogeropoulos, A.; Karacheban, O.; Kasemann, M.; Keaveney, J.; Kleinwort, C.; Korol, I.; Krücker, D.; Lange, W.; Lelek, A.; Lenz, T.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Mankel, R.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Roland, B.; Sahin, M. Ö.; Saxena, P.; SchoernerSadenius, T.; Spannagel, S.; Stefaniuk, N.; Van Onsem, G. P.; Walsh, R.; Wissing, C.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Dreyer, T.; Garutti, E.; Gonzalez, D.; Haller, J.; Hoffmann, M.; Junkes, A.; Klanner, R.; Kogler, R.; Kovalchuk, N.; Lapsien, T.; Marchesini, I.; Marconi, D.; Meyer, M.; Niedziela, M.; Nowatschin, D.; Pantaleo, F.; Peiffer, T.; Perieanu, A.; Scharf, C.; Schleper, P.; Schmidt, A.; Schumann, S.; Schwandt, J.; Stadie, H.; Steinbrück, G.; Stober, F. M.; Stöver, M.; Tholen, H.; Troendle, D.; Usai, E.; Vanelderen, L.; Vanhoefer, A.; Vormwald, B.; Akbiyik, M.; Barth, C.; Baur, S.; Baus, C.; Berger, J.; Butz, E.; Caspart, R.; Chwalek, T.; Colombo, F.; De Boer, W.; Dierlamm, A.; Fink, S.; Freund, B.; Friese, R.; Giffels, M.; Gilbert, A.; Goldenzweig, P.; Haitz, D.; Hartmann, F.; Heindl, S. M.; Husemann, U.; Kassel, F.; Katkov, I.; Kudella, S.; Mildner, H.; Mozer, M. U.; Müller, Th.; Plagge, M.; Quast, G.; Rabbertz, K.; Röcker, S.; Roscher, F.; Schröder, M.; Shvetsov, I.; Sieber, G.; Simonis, H. J.; Ulrich, R.; Wayand, S.; Weber, M.; Weiler, T.; Williamson, S.; Wöhrmann, C.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. A.; Kyriakis, A.; Loukas, D.; Topsis-Giotis, I.; Kesisoglou, S.; Panagiotou, A.; Saoulidou, N.; Tziaferi, E.; Evangelou, I.; Flouris, G.; Foudas, C.; Kokkas, P.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Filipovic, N.; Pasztor, G.; Bencze, G.; Hajdu, C.; Horvath, D.; Sikler, F.; Veszpremi, V.; Vesztergombi, G.; Zsigmond, A. J.; Beni, N.; Czellar, S.; Karancsi, J.; Makovec, A.; Molnar, J.; Szillasi, Z.; Bartók, M.; Raics, P.; Trocsanyi, Z. L.; Ujvari, B.; Komaragiri, J. R.; Bahinipati, S.; Bhowmik, S.; Choudhury, S.; Mal, P.; Mandal, K.; Nayak, A.; Sahoo, D. K.; Sahoo, N.; Swain, S. K.; Bansal, S.; Beri, S. B.; Bhatnagar, V.; Bhawandeep, U.; Chawla, R.; Kalsi, A. K.; Kaur, A.; Kaur, M.; Kumar, R.; Kumari, P.; Mehta, A.; Mittal, M.; Singh, J. B.; Walia, G.; Kumar, Ashok; Bhardwaj, A.; Choudhary, B. C.; Garg, R. B.; Keshri, S.; Malhotra, S.; Naimuddin, M.; Ranjan, K.; Sharma, R.; Sharma, V.; Bhattacharya, R.; Bhattacharya, S.; Chatterjee, K.; Dey, S.; Dutt, S.; Dutta, S.; Ghosh, S.; Majumdar, N.; Modak, A.; Mondal, K.; Mukhopadhyay, S.; Nandan, S.; Purohit, A.; Roy, A.; Roy, D.; Roy Chowdhury, S.; Sarkar, S.; Sharan, M.; Thakur, S.; Behera, P. K.; Chudasama, R.; Dutta, D.; Jha, V.; Kumar, V.; Mohanty, A. K.; Netrakanti, P. K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Dugad, S.; Kole, G.; Mahakud, B.; Mitra, S.; Mohanty, G. B.; Parida, B.; Sur, N.; Sutar, B.; Banerjee, S.; Dewanjee, R. K.; Ganguly, S.; Guchait, M.; Jain, Sa.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Sarkar, T.; Wickramage, N.; Chauhan, S.; Dube, S.; Hegde, V.; Kapoor, A.; Kothekar, K.; Pandey, S.; Rane, A.; Sharma, S.; Chenarani, S.; Eskandari Tadavani, E.; Etesami, S. M.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Calabria, C.; Caputo, C.; Colaleo, A.; Creanza, D.; Cristella, L.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; Miniello, G.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Ranieri, A.; Selvaggi, G.; Sharma, A.; Silvestris, L.; Venditti, R.; Verwilligen, P.; Abbiendi, G.; Battilana, C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Chhibra, S. S.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Sguazzoni, G.; Strom, D.; Viliani, L.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Primavera, F.; Calvelli, V.; Ferro, F.; Monge, M. R.; Robutti, E.; Tosi, S.; Brianza, L.; Brivio, F.; Ciriolo, V.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Ghezzi, A.; Govoni, P.; Malberti, M.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Pigazzini, S.; Ragazzi, S.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; De Nardo, G.; Di Guida, S.; Fabozzi, F.; Fienga, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Paolucci, P.; Sciacca, C.; Thyssen, F.; Azzi, P.; Bacchetta, N.; Benato, L.; Bisello, D.; Boletti, A.; Carlin, R.; Carvalho Antunes De Oliveira, A.; Checchia, P.; Dall'Osso, M.; De Castro Manzano, P.; Dorigo, T.; Dosselli, U.; Gasparini, F.; Gasparini, U.; Gozzelino, A.; Lacaprara, S.; Margoni, M.; Meneguzzo, A. T.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Torassa, E.; Zanetti, M.; Zotto, P.; Zumerle, G.; Braghieri, A.; Fallavollita, F.; Magnani, A.; Montagna, P.; Ratti, S. P.; Re, V.; Riccardi, C.; Salvini, P.; Vai, I.; Vitulo, P.; Alunni Solestizi, L.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Leonardi, R.; Mantovani, G.; Mariani, V.; Menichelli, M.; Saha, A.; Santocchia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Barone, L.; Cavallari, F.; Cipriani, M.; Del Re, D.; Diemoz, M.; Gelli, S.; Longo, E.; Margaroli, F.; Marzocchi, B.; Meridiani, P.; Organtini, G.; Paramatti, R.; Preiato, F.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bartosik, N.; Bellan, R.; Biino, C.; Cartiglia, N.; Cenna, F.; Costa, M.; Covarelli, R.; Degano, A.; Demaria, N.; Finco, L.; Kiani, B.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Monteil, E.; Monteno, M.; Obertino, M. M.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Ravera, F.; Romero, A.; Ruspa, M.; Sacchi, R.; Shchelina, K.; Sola, V.; Solano, A.; Staiano, A.; Traczyk, P.; Belforte, S.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Zanetti, A.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Lee, S.; Lee, S. W.; Oh, Y. D.; Sekmen, S.; Son, D. C.; Yang, Y. C.; Lee, A.; Kim, H.; Brochero Cifuentes, J. A.; Kim, T. J.; Cho, S.; Choi, S.; Go, Y.; Gyun, D.; Ha, S.; Hong, B.; Jo, Y.; Kim, Y.; Lee, K.; Lee, K. S.; Lee, S.; Lim, J.; Park, S. K.; Roh, Y.; Almond, J.; Kim, J.; Lee, H.; Oh, S. B.; Radburn-Smith, B. C.; Seo, S. h.; Yang, U. K.; Yoo, H. D.; Yu, G. B.; Choi, M.; Kim, H.; Kim, J. H.; Lee, J. S. H.; Park, I. C.; Ryu, G.; Ryu, M. S.; Choi, Y.; Goh, J.; Hwang, C.; Lee, J.; Yu, I.; Dudenas, V.; Juodagalvis, A.; Vaitkus, J.; Ahmed, I.; Ibrahim, Z. A.; Md Ali, M. A. B.; Mohamad Idris, F.; Wan Abdullah, W. A. T.; Yusli, M. N.; Zolkapli, Z.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-De La Cruz, I.; Hernandez-Almada, A.; Lopez-Fernandez, R.; Magaña Villalba, R.; Mejia Guisao, J.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Oropeza Barrera, C.; Vazquez Valencia, F.; Carpinteyro, S.; Pedraza, I.; Salazar Ibarguen, H. A.; Uribe Estrada, C.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khan, W. A.; Saddique, A.; Shah, M. A.; Shoaib, M.; Waqas, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Bunkowski, K.; Byszuk, A.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Walczak, M.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Calpas, B.; Di Francesco, A.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Hollar, J.; Leonardo, N.; Lloret Iglesias, L.; Nemallapudi, M. 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2017-10-01

Jet charge is an estimator of the electric charge of a quark, antiquark, or gluon initiating a jet. It is based on the momentum-weighted sum of the electric charges of the jet constituents. Measurements of three charge observables of the leading jet in transverse momentum p T are performed with dijet events. The analysis is carried out with ata collected by the CMS experiment at the CERN LHC in proton-proton collisions at √{s}=8 TeV corresponding to an integrated luminosity of 19.7fb-1. The results are presented as a function of the p T of the leading jet and compared to predictions from leading- and next-to-leading-order event generators combined with parton showers. Measured jet charge distributions, unfolded for detector effects, are reported, which expand on previous measurements of the jet charge average and standard deviation in pp collisions. [Figure not available: see fulltext.

Signal transduction at fertilization: the Ca2+ release pathway in echinoderms and other invertebrate deuterostomes.

PubMed

Townley, Ian K; Roux, Michelle M; Foltz, Kathy R

2006-04-01

Gamete interaction and fusion triggers a number of events that lead to egg activation and development of a new organism. A key event at fertilization is the rise in intracellular calcium. In deuterostomes, this calcium is released from the egg's endoplasmic reticulum and is necessary for proper activation. This article reviews recent data regarding how gamete interaction triggers the initial calcium release, focusing on the echinoderms (invertebrate deuterostomes) as model systems. In eggs of these animals, Src-type kinases and phospholipase C-gamma are required components of the initial calcium trigger pathway in eggs.

Black Hole Paradoxes

NASA Astrophysics Data System (ADS)

Joshi, Pankaj S.; Narayan, Ramesh

2016-10-01

We propose here that the well-known black hole paradoxes such as the information loss and teleological nature of the event horizon are restricted to a particular idealized case, which is the homogeneous dust collapse model. In this case, the event horizon, which defines the boundary of the black hole, forms initially, and the singularity in the interior of the black hole at a later time. We show that, in contrast, gravitational collapse from physically more realistic initial conditions typically leads to the scenario in which the event horizon and space-time singularity form simultaneously. We point out that this apparently simple modification can mitigate the causality and teleological paradoxes, and also lends support to two recently suggested solutions to the information paradox, namely, the ‘firewall’ and ‘classical chaos’ proposals.

Discovering the route from inflammation to pancreatic cancer

PubMed Central

MOMI, N.; KAUR, S.; KRISHN, S. R.; BATRA, S. K.

2013-01-01

Pancreatic cancer (PC) remains a complex malignancy with the worst prognosis, lack of early diagnostic symptoms and resistance to conventional chemo- and radiotherapies. A better understanding of the etiology and early developmental events of PC requires profound attention. The evolution of fully blown PC from initial pancreatic injury is a multi-factorial phenomenon with a series of sequential events. The initial acute infection or tissue damage triggers inflammation that, in conjunction with innate immunity, establishes a state of homeostasis to limit harm to the body. Recurrent pancreatic injuries due to genetic susceptibility, smoking, unhealthy diet, and alcohol abuse induces a pro-inflammatory milieu, consisting of various types of immune cells, cytokines, chemokines, growth factors and restructured extracellular matrix, leading to prolonged inflammatory/chronic conditions. Cells having sustained DNA damage and/or mutagenic assault take advantage of this prolonged inflammatory response and aid in the initiation and development of neoplastic/fibrotic events. Eventually, many tumor-stromal interactions result in a chaotic environment accompanied by a loss of immune surveillance and repair response, thereby leading to PC. A better understanding of the inflammatory markers defining this “injury-inflammation-cancer” pathway would help to identify novel molecular targets for early screening and therapeutic intervention for this lethal malignancy. PMID:23207606

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rison, William; Krehbiel, Paul R.; Stock, Michael G.

A long-standing but fundamental question in lightning studies concerns how lightning is initiated inside storms, given the absence of physical conductors. The issue has revolved around the question of whether the discharges are initiated solely by conventional dielectric breakdown or involve relativistic runaway electron processes. Here we report observations of a relatively unknown type of discharge, called fast positive breakdown, that is the cause of high-power discharges known as narrow bipolar events. We find that the breakdown has a wide range of strengths and is the initiating event of numerous lightning discharges. It appears to be purely dielectric in naturemore » and to consist of a system of positive streamers in a locally intense electric field region. It initiates negative breakdown at the starting location of the streamers, which leads to the ensuing flash. The observations show that many or possibly all lightning flashes are initiated by fast positive breakdown.« less

Fast Positive Breakdown, NBEs, and Lightning Initiation

NASA Astrophysics Data System (ADS)

Krehbiel, P. R.; Rison, W.; Stock, M.; Edens, H. E.; Shao, X. M.; Thomas, R. J.; Stanley, M. A.; Zhang, Y.

2016-12-01

High power narrrow bipolar events (NBEs) have been found to be produced by arelatively unknown type of discharge, called fast positive breakdown (Rison etal., 2016). The breakdown occurs with a wide range of strengths, both in terms of its broadband sferic and its VHF radiation, and is found to be theinitiating event of many and likely all lightning discharges inside storms. Itdoes not produce a conducting channel but instead appears to be produced by avolumetric system of repeated, cascading positive streamers in virgin air.That positive corona and streamers would be responsible for initiatinglightning was proposed in the 1960s by Loeb, Dawson and Winn. In the 1970sPhelps and Griffiths showed that the streamers would be self-intensifying,leading to negative breakdown being initiated back at their starting points.Petersen et al. (2008) described experimental results showing that thestreamers could be initiated by ice crystals at cold temperatures, and thephysical processes leading to the breakdown being fast has been reported inrecent modeling studies by Shi et al. (2016). In this paper we summarize the observational data in support of the abovefindings, and report on additional observations of NBEs and lightninginitiation currently being obtained at Kennedy Space Center, Florida. References: Rison W., P.R. Krehbiel M.G.Stock, H.E. Edens, X-M. Shao, R.J. Thomas,M.A. Stanley, Y. Zhang, Observations of narrow bipolar events revealhow lightning is initiated in thunderstorms, Nature Comms. 7, 2016.doi:10.1038/ncomms10721. Petersen, D., Bailey, M., Beasley, W. & Hallett, J. A brief review ofthe problem of lightning initiation and a hypothesis of initiallightning leader formation. J. Geophys. Res. 113, D17205 (2008). Shi, F., N. Liu, and H. K. Rassoul (2016), Properties of relativelylong streamers initiated from an isolated hydrometeor, J. Geophys.Res. Atmos., 121, 7284-7295, doi:10.1002/2015JD024580.

Receptor tyrosine kinase alterations in AML - biology and therapy.

PubMed

Stirewalt, Derek L; Meshinchi, Soheil

2010-01-01

Acute myeloid leukemia (AML) is the most common form of leukemia in adults, and despite some recent progress in understanding the biology of the disease, AML remains the leading cause of leukemia-related deaths in adults and children. AML is a complex and heterogeneous disease, often involving multiple genetic defects that promote leukemic transformation and drug resistance. The cooperativity model suggests that an initial genetic event leads to maturational arrest in a myeloid progenitor cell, and subsequent genetic events induce proliferation and block apoptosis. Together, these genetic abnormalities lead to clonal expansion and frank leukemia. The purpose of this chapter is to review the biology of receptor tyrosine kinases (RTKs) in AML, exploring how RTKs are being used as novel prognostic factors and potential therapeutic targets.

Color Coherent Radiation in Multi - Jet Events from $$p\\overline{p}$$ Collisions at $$\\sqrt{s}$$ = 1.8-TeV

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cullen-Vidal, David Edward

1997-01-01

Results from a study of color coherence phenomena in multi-jet events produced bymore » $$p\\overline{p}$$ collisions are presented. Approximately 13 $$pb^{-1}$$ of data were collected by the D0 detector during the 1992-1993 run of the Fermilab Tevatron $$p\\overline{p}$$ collider at a center of mass energy of $$\\sqrt{s}$$ = 1.8 TeV. Demonstration of initial-to-final state color interference effects is done by measuring spatial correlations between the softer third jet and the second leading-$$E_{\\tau}$$ jet in the events. The data are compared to several Monte Carlo simulations with different color coherence implementations and to the predictions of a Next-to-Leading Order parton level calculation.« less

Tolerability of sibutramine during a 6-week treatment period in high-risk patients with cardiovascular disease and/or diabetes: a preliminary analysis of the Sibutramine Cardiovascular Outcomes (SCOUT) Trial.

PubMed

Maggioni, Aldo P; Caterson, Ian; Coutinho, Walmir; Finer, Nick; Gaal, Luc Van; Sharma, Arya M; Torp-Pedersen, Christian; Bacher, Peter; Shepherd, Gillian; Sun, Rui; James, Philip

2008-11-01

Uncertainties about the cardiovascular safety of sibutramine led to the SCOUT trial that is investigating sibutramine plus weight management in high-risk, overweight/obese patients. A 6-week lead-in period during which all patients received sibutramine permitted an initial assessment of tolerability. A total of 10,742 patients received sibutramine and 3.1% of these discontinued due to an adverse event; issues affecting more than 10 patients were drug intolerance, headache, insomnia, nausea, dry mouth, and constipation-, tachycardia-, and hypertension-related events. Serious adverse events, most commonly associated with the System Organ Class, Cardiac disorders, were reported by 2.7% of patients; however, the majority was not considered sibutramine-related. Adverse events relating to high blood pressure and/or pulse rate, whether reported as adverse events leading to discontinuation, or serious adverse events were reported by less than 0.2% of patients. No serious or individual events leading to discontinuation occurred in more than 25 patients. There were 15 (0.1%) deaths; 10 were attributed to a cardiovascular cause. Discontinuations for adverse events were lower than anticipated. Serious adverse events generally reflected sibutramine's known pharmacology or were related to cardiac disorders already present in this high-risk population. When compared with epidemiological data, overall mortality rate was low and sibutramine was well tolerated in this mainly off-label population. No new safety issues were detected.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sirunyan, A. M.; Tumasyan, A.; Adam, W.

Here, jet charge is an estimator of the electric charge of a quark, antiquark, or gluon initiating a jet. It is based on the momentum-weighted sum of the electric charges of the jet constituents. Measurements of three charge observables of the leading jet in transverse momentum pT are performed with dijet events. The analysis is carried out with data collected by the CMS experiment at the CERN LHC in proton-proton collisions at √s = 8 TeV corresponding to an integrated luminosity of 19.7fb -1. The results are presented as a function of the pT of the leading jet and comparedmore » to predictions from leading- and next-to-leading-order event generators combined with parton showers. Measured jet charge distributions, unfolded for detector effects, are reported, which expand on previous measurements of the jet charge average and standard deviation in pp collisions.« less

Adverse Outcome Pathways for Regulatory Applications: Examination of Four Case Studies With Different Degrees of Completeness and Scientific Confidence.

PubMed

Perkins, Edward J; Antczak, Philipp; Burgoon, Lyle; Falciani, Francesco; Garcia-Reyero, Natàlia; Gutsell, Steve; Hodges, Geoff; Kienzler, Aude; Knapen, Dries; McBride, Mary; Willett, Catherine

2015-11-01

Adverse outcome pathways (AOPs) offer a pathway-based toxicological framework to support hazard assessment and regulatory decision-making. However, little has been discussed about the scientific confidence needed, or how complete a pathway should be, before use in a specific regulatory application. Here we review four case studies to explore the degree of scientific confidence and extent of completeness (in terms of causal events) that is required for an AOP to be useful for a specific purpose in a regulatory application: (i) Membrane disruption (Narcosis) leading to respiratory failure (low confidence), (ii) Hepatocellular proliferation leading to cancer (partial pathway, moderate confidence), (iii) Covalent binding to proteins leading to skin sensitization (high confidence), and (iv) Aromatase inhibition leading to reproductive dysfunction in fish (high confidence). Partially complete AOPs with unknown molecular initiating events, such as 'Hepatocellular proliferation leading to cancer', were found to be valuable. We demonstrate that scientific confidence in these pathways can be increased though the use of unconventional information (eg, computational identification of potential initiators). AOPs at all levels of confidence can contribute to specific uses. A significant statistical or quantitative relationship between events and/or the adverse outcome relationships is a common characteristic of AOPs, both incomplete and complete, that have specific regulatory uses. For AOPs to be useful in a regulatory context they must be at least as useful as the tools that regulators currently possess, or the techniques currently employed by regulators. Published by Oxford University Press on behalf of the Society of Toxicology 2015. This work is written by US Government employees and is in the public domain in the US.

Evaluating iodide recycling inhibition as a novel molecular initiating event for thyroid axis disruption

EPA Science Inventory

The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces available iodide for thyroid hormone synthesis, which leads to hormone insufficiency...

Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.

PubMed

Hopkin, Robert J; Cabrera, Gustavo; Charrow, Joel; Lemay, Roberta; Martins, Ana Maria; Mauer, Michael; Ortiz, Alberto; Patel, Manesh R; Sims, Katherine; Waldek, Stephen; Warnock, David G; Wilcox, William R

2016-09-01

Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death. This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death. The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free. Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

INTERNAL HAZARDS ANALYSIS FOR LICENSE APPLICATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

R.J. Garrett

2005-02-17

The purpose of this internal hazards analysis is to identify and document the internal hazards and potential initiating events associated with preclosure operations of the repository at Yucca Mountain. Internal hazards are those hazards presented by the operation of the facility and by its associated processes that can potentially lead to a radioactive release or cause a radiological hazard. In contrast to external hazards, internal hazards do not involve natural phenomena and external man-made hazards. This internal hazards analysis was performed in support of the preclosure safety analysis and the License Application for the Yucca Mountain Project. The methodology formore » this analysis provides a systematic means to identify internal hazards and potential initiating events that may result in a radiological hazard or radiological release during the repository preclosure period. These hazards are documented in tables of potential internal hazards and potential initiating events (Section 6.6) for input to the repository event sequence categorization process. The results of this analysis will undergo further screening and analysis based on the criteria that apply to the performance of event sequence analyses for the repository preclosure period. The evolving design of the repository will be re-evaluated periodically to ensure that internal hazards that have not been previously evaluated are identified.« less

Mathematical Modeling of Early Cellular Innate and Adaptive Immune Responses to Ischemia/Reperfusion Injury and Solid Organ Allotransplantation

PubMed Central

Day, Judy D.; Metes, Diana M.; Vodovotz, Yoram

2015-01-01

A mathematical model of the early inflammatory response in transplantation is formulated with ordinary differential equations. We first consider the inflammatory events associated only with the initial surgical procedure and the subsequent ischemia/reperfusion (I/R) events that cause tissue damage to the host as well as the donor graft. These events release damage-associated molecular pattern molecules (DAMPs), thereby initiating an acute inflammatory response. In simulations of this model, resolution of inflammation depends on the severity of the tissue damage caused by these events and the patient’s (co)-morbidities. We augment a portion of a previously published mathematical model of acute inflammation with the inflammatory effects of T cells in the absence of antigenic allograft mismatch (but with DAMP release proportional to the degree of graft damage prior to transplant). Finally, we include the antigenic mismatch of the graft, which leads to the stimulation of potent memory T cell responses, leading to further DAMP release from the graft and concomitant increase in allograft damage. Regulatory mechanisms are also included at the final stage. Our simulations suggest that surgical injury and I/R-induced graft damage can be well-tolerated by the recipient when each is present alone, but that their combination (along with antigenic mismatch) may lead to acute rejection, as seen clinically in a subset of patients. An emergent phenomenon from our simulations is that low-level DAMP release can tolerize the recipient to a mismatched allograft, whereas different restimulation regimens resulted in an exaggerated rejection response, in agreement with published studies. We suggest that mechanistic mathematical models might serve as an adjunct for patient- or sub-group-specific predictions, simulated clinical studies, and rational design of immunosuppression. PMID:26441988

An integrated approach towards identifying age-related mechanisms of slip initiated falls

PubMed Central

Lockhart, Thurmon E.

2008-01-01

The causes of slip and fall accidents, both in terms of extrinsic and intrinsic factors and their associations are not yet fully understood. Successful intervention solutions for reducing slip and fall accidents require a more complete understanding of the mechanisms involved. Before effective fall prevention strategies can be put into practice, it is central to examine the chain of events in an accident, comprising the exposure to hazards, initiation of events and the final outcome leading to injury and disability. These events can be effectively identified and analyzed by applying epidemiological, psychophysical, biomechanical and tribological research principles and methodologies. In this manuscript, various methods available to examine fall accidents and their underlying mechanisms are presented to provide a comprehensive array of information to help pinpoint the needs and requirements of new interventions aimed at reducing the risk of falls among the growing elderly population. PMID:17768070

Thoughts Without Content are Empty, Intuitions Without Concepts are Blind - Determinism and Contingency Revisited

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2011-01-01

Was the emergence of life a predictable outcome of chemical evolution on earth? Could evolution produce life very different from ours? These are one of the oldest questions in the field of the origin of life that not only have broad philosophical implications but also impact how we approach the problem from the methodological standpoint. Framing the issue in terms of the dichotomy between contingency and determinism is not a fortunate because these two terms in their conventional meaning are neither mutually exclusive nor jointly exhaustive. Determinism, represented in natural sciences by Newtonian physics, relies on the assumption that every event is causally determined by a chain of previous events. In the context of the origin of life it means that once the initial conditions on the early earth have been specified further evolution follows inevitably. Considering uncertainties about conditions on the prebiotic earth, many plausible sets of initial conditions can be defined, each followed by a separate deterministic trajectory. This conventional understanding of determinism does not admit contingency. Further, it has no implications for evaluating how many sets of initial conditions lead to the emergence of life. It appears that a better framing of the problem is as follows: given plausible sets of initial conditions on the early earth how probable and broadly spread are evolutionary trajectories that lead to life? Instead of undertaking an impossible task of specifying microscopic initial conditions for all components of the system one uses a reduced representation of this system and specify only a small set of essential macroscopic parameters, values (or ranges of values) of which can be identified, inferred or estimated from experiment, theory or historical record. The following evolutionary trajectories are still governed by laws of physics and chemistry but become probabilistic and "contingency" is admitted as variations in other variables in the system. A similar reasoning is common in other fields of science, for example in statistical mechanics. Some trajectories lead to life, perhaps in different forms, whereas others do not. Of our true interest is the ratio of these two outcomes. The issue of determinism does not directly enter the picture. The debate about the likelihood of the emergence of life is quite old. One view holds that the origin of life is an event governed by chance, and the result of so many random events (contingencies) is unpredictable. This view was eloquently expressed by Monod. In his book "Chance or Necessity" he argued that life was a product of "nature's roulette." In an alternative view, expressed in particular by deDuve and Morowitz, the origin of life is considered a highly probable or even inevitable event (although its details need not be determined in every respect). Only in this sense the origin of life can be considered a "deterministic event".

76 FR 72559 - Enhancements to Emergency Preparedness Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-23

... allow the assignment of the on-shift health physics technician (HP Tech.) as the interim operations... public health and safety. These modifications were issued to licensees by NRC Order EA-02-026, ``Order... health and safety through improvements in the response to unlikely initiating events that could lead to...

Cross-species analysis of thyroperoxidase inhibition by xenobiotics demonstrates conservation of response between pig and rat

EPA Science Inventory

Thyroperoxidase (TPO), the enzyme that catalyzes the synthesis of thyroid hormone (TH), is a known target for thyroid-disrupting chemicals (TDC). In vivo toxicological evidence supporting TPO-inhibition as one molecular-initiating event that leads to thyroid disruption is derive...

Assistant Principal Dilemma: Walking the Line between Compliance and Leadership

ERIC Educational Resources Information Center

Baker, A. Minor; Guerra, Patricia L.; Baray, Sarah

2018-01-01

Inspired by real-life events, this case describes the start of a seemingly solid working relationship between two elementary campus administrators and its demise as the result of inadequate communication and distrust. Initially, these two leaders benefit from differing supervision styles, but these differences eventually lead to increased tension…

PUTATIVE ADVERSE OUTCOME PATHWAY FOR INHIBITON OF BRAIN AROMATASE IN FISH LEADING TO REPRODUCTIVE IMPAIRMENT

EPA Science Inventory

The adverse outcome pathway (AOP) provides a framework for organizing knowledge to define links between a molecular initiating event (MIE) and an adverse outcome (AO) occurring at a higher level of biological organization, such as the individual or population. The AOP framework p...

KENNEDY SPACE CENTER, FLA. - At the rollout of the One NASA initiative at KSC, Glenn Research Center Director Dr. Julian Earls embraces implementation team lead Johnny Stevenson while KSC Director Jim Kennedy (left) applauds. Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Kennedy and Earls, were James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson.

NASA Image and Video Library

2003-08-20

KENNEDY SPACE CENTER, FLA. - At the rollout of the One NASA initiative at KSC, Glenn Research Center Director Dr. Julian Earls embraces implementation team lead Johnny Stevenson while KSC Director Jim Kennedy (left) applauds. Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Kennedy and Earls, were James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson.

Identifying Gaps and Launching Resident Wellness Initiatives: The 2017 Resident Wellness Consensus Summit.

PubMed

Zaver, Fareen; Battaglioli, Nicole; Denq, William; Messman, Anne; Chung, Arlene; Lin, Michelle; Liu, Emberlynn L

2018-03-01

Burnout, depression, and suicidality among residents of all specialties have become a critical focus for the medical education community, especially among learners in graduate medical education. In 2017 the Accreditation Council for Graduate Medical Education (ACGME) updated the Common Program Requirements to focus more on resident wellbeing. To address this issue, one working group from the 2017 Resident Wellness Consensus Summit (RWCS) focused on wellness program innovations and initiatives in emergency medicine (EM) residency programs. Over a seven-month period leading up to the RWCS event, the Programmatic Initiatives workgroup convened virtually in the Wellness Think Tank, an online, resident community consisting of 142 residents from 100 EM residencies in North America. A 15-person subgroup (13 residents, two faculty facilitators) met at the RWCS to develop a public, central repository of initiatives for programs, as well as tools to assist programs in identifying gaps in their overarching wellness programs. An online submission form and central database of wellness initiatives were created and accessible to the public. Wellness Think Tank members collected an initial 36 submissions for the database by the time of the RWCS event. Based on general workplace, needs-assessment tools on employee wellbeing and Kern's model for curriculum development, a resident-based needs-assessment survey and an implementation worksheet were created to assist residency programs in wellness program development. The Programmatic Initiatives workgroup from the resident-driven RWCS event created tools to assist EM residency programs in identifying existing initiatives and gaps in their wellness programs to meet the ACGME's expanded focus on resident wellbeing.

The Influence of Object Conceptions on the Mechanical Intuitions of Children and Adults.

ERIC Educational Resources Information Center

Rosser, Rosemary A.; Chandler, Kacey

1995-01-01

Examined how children's and adults' initial conceptions of objects and space influence predictions about the physical world, but lead the naive person to misconstrue a dynamic event. Found that participants proficiently anticipated where an oscillating screen would contact a hidden object, but underestimated the distance until contact.…

Application of adverse outcome pathways (AOPs) in human health and ecotoxicology capturing divergent consequences of conserved molecular initiating events via AOP networks

EPA Science Inventory

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

Application of Adverse Outcome Pathways (AOPs) in Human Health and Ecotoxicology Capturing Divergent Consequences of Conserved Molecular Initiating Events via AOP Networks (Presentation)

EPA Science Inventory

The adverse outcome pathway (AOP) framework was developed to help organize and disseminate existing knowledge concerning the means through which specific perturbations of biological pathways can lead to adverse outcomes considered relevant to risk-based regulatory decision-making...

Use of Modal Acoustic Emission to Monitor Damage Progression in Carbon Fiber/Epoxy Tows and Implications for Composite Structures

NASA Technical Reports Server (NTRS)

Waller, Jess M.; Saulsberry, Regor L.; Lucero, Ralph; Nichols, Charles T.; Wentzel, Daniel J.

2010-01-01

ASTM-based ILH methods were found to give a reproducible, quantitative estimate of the stress threshold at which significant accumulated damage began to occur. a) FR events are low energy (<2 V(exp 20 microsec) b) FR events occur close to the observed failure locus. c) FR events consist of more than 30% fiber breakage (>300 kHz) d) FR events show a consistent hierarchy of cooperative damage for composite tow, and for the COPV tested, regardless of applied load. Application of ILH or related stress profiles could lead to robust pass/fail acceptance criteria based on the FR. Initial application of FR and FFT analysis of AE data acquired on COPVs is promising.

A synoptic climatology of derecho producing mesoscale convective systems in the North-Central Plains

NASA Astrophysics Data System (ADS)

Bentley, Mace L.; Mote, Thomas L.; Byrd, Stephen F.

2000-09-01

Synoptic-scale environments favourable for producing derechos, or widespread convectively induced windstorms, in the North-Central Plains are examined with the goal of providing pattern-recognition/diagnosis techniques. Fifteen derechos were identified across the North-Central Plains region during 1986-1995. The synoptic environment at the initiation, mid-point and decay of each derecho was then evaluated using surface, upper-air and National Center for Atmospheric Research (NCAR)/National Center for Environmental Prediction (NCEP) reanalysis datasets.Results suggest that the synoptic environment is critical in maintaining derecho producing mesoscale convective systems (DMCSs). The synoptic environment in place downstream of the MCS initiation region determines the movement and potential strength of the system. Circulation around surface low pressure increased the instability gradient and maximized leading edge convergence in the initiation region of nearly all events regardless of DMCS location or movement. Other commonalities in the environments of these events include the presence of a weak thermal boundary, high convective instability and a layer of dry low-to-mid-tropospheric air. Of the two corridors sampled, northeastward moving derechos tend to initiate east of synoptic-scale troughs, while southeastward moving derechos form on the northeast periphery of a synoptic-scale ridge. Other differences between these two DMCS events are also discussed.

Numerical simulations of an advection fog event over Shanghai Pudong International Airport with the WRF model

NASA Astrophysics Data System (ADS)

Lin, Caiyan; Zhang, Zhongfeng; Pu, Zhaoxia; Wang, Fengyun

2017-10-01

A series of numerical simulations is conducted to understand the formation, evolution, and dissipation of an advection fog event over Shanghai Pudong International Airport (ZSPD) with the Weather Research and Forecasting (WRF) model. Using the current operational settings at the Meteorological Center of East China Air Traffic Management Bureau, the WRF model successfully predicts the fog event at ZSPD. Additional numerical experiments are performed to examine the physical processes associated with the fog event. The results indicate that prediction of this particular fog event is sensitive to microphysical schemes for the time of fog dissipation but not for the time of fog onset. The simulated timing of the arrival and dissipation of the fog, as well as the cloud distribution, is substantially sensitive to the planetary boundary layer and radiation (both longwave and shortwave) processes. Moreover, varying forecast lead times also produces different simulation results for the fog event regarding its onset and duration, suggesting a trade-off between more accurate initial conditions and a proper forecast lead time that allows model physical processes to spin up adequately during the fog simulation. The overall outcomes from this study imply that the complexity of physical processes and their interactions within the WRF model during fog evolution and dissipation is a key area of future research.

Precipitation Phase Partitioning during Inland Penetrating Atmospheric River events: Role of Initial Land Surface Conditions

NASA Astrophysics Data System (ADS)

Rudisill, W. J.; Flores, A. N.; FitzGerald, K.; Masarik, M. T.

2017-12-01

In the Western US, the occurrence (or lack thereof) of a handful of cool-season Atmospheric River (AR) events exerts significant controls on the seasonal water budget in many watersheds. The occurrence of these ARs can serve to alleviate drought and can also lead to significant flooding. In winter seasons, ARs typically bring warmer than average conditions and both rain and snow. To date, there has been little effort to understand how the land surface hydrological states prior to and during the arrival of ARs, acting on the surface water and energy balance, impact the onset, extent, and evolution of precipitation intensity and phase during AR events. While precipitation arriving as snow can contribute to seasonal snowpacks that lead to runoff later in hot/dry seasons, liquid precipitation can contribute to more rapid runoff or deplete existing snowpacks. The latter case, in which latent and advected heat from fallen rain causes snowmelt, is a key mechanism of flood and landslide-producing runoff in the Western United States. Motivated by an extensive, flood producing AR in 2010, we examine the sensitivity of hydrometeor phase to land surface forcings (sensible/latent heating, short/longwave radiation) using the WRF (Weather Research and Forecasting) model in Central Idaho. Specifically, we evaluate whether pre-existing snow covered area extent, snow water equivalent (SWE), and cold-content influence the partitioning of precipitation into solid and liquid phases during inland AR events. Our experimental design leverages a long-term coupled land-atmosphere simulation with WRF over the study domain in order to evaluate how a set of particular AR events evolve when exposed to initial land surface states capturing a broad range of climatological conditions during the past 30 years.

BWR Anticipated Transients Without Scram Leading to Instability

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng L. Y.; Baek J.; Cuadra, A.

2013-11-10

Anticipated transients without scram (ATWS) in aboiling water reactor (BWR) were simulated in order to understand reactor response and determine the effectiveness of automatic and operator actions to mitigate this beyond-design-basis accident. The events of interest herein are initiated by a turbine trip when the reactor is operating in the expanded operating domainMELLLA+ [maximum extended load line limit plus]. In these events the reactor may initially be at up to 120% of the original licensed thermal power (OLTP) and at flow rates as low as 80% of rated.For these (and similar) ATWS events the concern isthat when the reactor powermore » decreases in response to a dual recirculation pump trip, the core will become unstable and large amplitude oscillations will begin. The occurrence of these power oscillations, if left unmitigated, may result in fuel damage, and the amplitude of the poweroscillations may hamper the effectiveness of the injection of dissolved neutron absorber through the standby liquid control system (SLCS).« less

Episodic Southern Ocean Heat Loss and Its Mixed Layer Impacts Revealed by the Farthest South Multiyear Surface Flux Mooring

NASA Astrophysics Data System (ADS)

Ogle, S. E.; Tamsitt, V.; Josey, S. A.; Gille, S. T.; Cerovečki, I.; Talley, L. D.; Weller, R. A.

2018-05-01

The Ocean Observatories Initiative air-sea flux mooring deployed at 54.08°S, 89.67°W, in the southeast Pacific sector of the Southern Ocean, is the farthest south long-term open ocean flux mooring ever deployed. Mooring observations (February 2015 to August 2017) provide the first in situ quantification of annual net air-sea heat exchange from one of the prime Subantarctic Mode Water formation regions. Episodic turbulent heat loss events (reaching a daily mean net flux of -294 W/m2) generally occur when northeastward winds bring relatively cold, dry air to the mooring location, leading to large air-sea temperature and humidity differences. Wintertime heat loss events promote deep mixed layer formation that lead to Subantarctic Mode Water formation. However, these processes have strong interannual variability; a higher frequency of 2 σ and 3 σ turbulent heat loss events in winter 2015 led to deep mixed layers (>300 m), which were nonexistent in winter 2016.

Population growth as a driver of initial domestication in Eastern North America

PubMed Central

Codding, Brian F.

2016-01-01

The transition to agriculture is one of the most significant events in human prehistory; yet, explaining why people initially domesticated plants and animals remains a contentious research problem in archaeology. Two competing hypotheses dominate current debates. The first draws on niche construction theory to emphasize how intentional management of wild resources should lead to domestication regardless of Malthusian population–resource imbalances. The second relies on models from behavioural ecology (BE) to highlight how individuals should only exert selective pressure on wild resources during times of population–resource imbalance. We examine these hypotheses to explain the domestication event which occurred in Eastern North America approximately 5000 years ago. Using radiocarbon date density and site counts as proxies for human population, we find that populations increased significantly in the 1000 years prior to initial domestication. We therefore suggest that high populations prior to 5000 cal BP may have experienced competition for and possibly overexploitation of resources, altering the selective pressures on wild plants thereby producing domesticates. These findings support the BE hypothesis of domestication occurring in the context of population–resource imbalances. Such deficits, driven either by increased populations or decreased resource abundance, are predicted to characterize domestication events elsewhere. PMID:27853610

Adapting biomarker technologies to adverse outcome pathways (AOPs) research: current thoughts on using in vivo discovery for developing in vitro target methods

EPA Science Inventory

Adverse outcome pathways (AOP) research is a relatively new concept in human systems biology for assessing the molecular level linkage from an initiating (chemical) event that could lead to a disease state. Although most implementations of AOPs are based on liquids analyses, the...

Systematic Review of Treatment for Trapped Thrombus in Patent Foramen Ovale.

PubMed

Seo, Won-Woo; Kim, Sung Eun; Park, Myung-Soo; Lee, Jun-Hee; Park, Dae-Gyun; Han, Kyoo-Rok; Oh, Dong-Jin

2017-09-01

Trapped thrombus in patent foramen ovale (PFO) is a rare complication of pulmonary embolism that may lead to tragic clinical events. The aim of this study was to identify the optimal treatment for different clinical situations in patients with trapped thrombus in a PFO by conducting a literature review. A PubMed database search was conducted from 1991 through 2015, and 194 patients (185 articles) with trapped thrombus in a PFO were identified. Patient characteristics, paradoxical embolic events, and factors affecting 60-day mortality were analyzed retrospectively. Among all patients, 112 (57.7%) were treated with surgery, 28 with thrombolysis, and 54 with anticoagulation alone. Dyspnea (79.4%), chest pain (33.0%), and syncope (17.5%) were the most common presenting symptoms. Pretreatment embolism was found in 37.6% of cases, and stroke (24.7%) was the most common event. Surgery was associated with fewer post-treatment embolic events than were other treatment options (p=0.044). In the multivariate analysis, initial shock or arrest, and thrombolysis were independent predictors of 60-day mortality. Thrombolysis was related with higher 60-day mortality compared with surgery in patients who had no initial shock or arrest. This systematic review showed that surgery was associated with a lower overall incidence of post-treatment embolic events and a lower 60-day mortality in patients with trapped thrombus in a PFO. In patients without initial shock or arrest, thrombolysis was related with a higher 60-day mortality compared with surgery.

Nanoengineered surfaces for focal adhesion guidance trigger mesenchymal stem cell self-organization and tenogenesis.

PubMed

Iannone, Maria; Ventre, Maurizio; Formisano, Lucia; Casalino, Laura; Patriarca, Eduardo J; Netti, Paolo A

2015-03-11

The initial conditions for morphogenesis trigger a cascade of events that ultimately dictate structure and functions of tissues and organs. Here we report that surface nanopatterning can control the initial assembly of focal adhesions, hence guiding human mesenchymal stem cells (hMSCs) through the process of self-organization and differentiation. This process self-sustains, leading to the development of macroscopic tissues with molecular profiles and microarchitecture reminiscent of embryonic tendons. Therefore, material surfaces can be in principle engineered to set off the hMSC program toward tissuegenesis in a deterministic manner by providing adequate sets of initial environmental conditions.

The Extracellular Matrix Regulates Granuloma Necrosis in Tuberculosis.

PubMed

Al Shammari, Basim; Shiomi, Takayuki; Tezera, Liku; Bielecka, Magdalena K; Workman, Victoria; Sathyamoorthy, Tarangini; Mauri, Francesco; Jayasinghe, Suwan N; Robertson, Brian D; D'Armiento, Jeanine; Friedland, Jon S; Elkington, Paul T

2015-08-01

A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of tuberculosis pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human tuberculosis granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase 1 causes caseous necrosis, the pathological hallmark of human tuberculosis. Collagen destruction is the principal pathological difference between humanised mice and wild-type mice with tuberculosis, whereas the release of proinflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of tuberculosis granuloma formation, using bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed on the basis of a lactate dehydrogenase release assay, propidium iodide staining, and measurement of the total number of viable cells. Taken together, these findings suggest that collagen destruction is an initial event in tuberculosis immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Is there an optimal level of open-endedness in prebiotic evolution?

PubMed

Markovitch, Omer; Sorek, Daniel; Lui, Leong Ting; Lancet, Doron; Krasnogor, Natalio

2012-10-01

In this paper we explore the question of whether there is an optimal set up for a putative prebiotic system leading to open-ended evolution (OEE) of the events unfolding within this system. We do so by proposing two key innovations. First, we introduce a new index that measures OEE as a function of the likelihood of events unfolding within a universe given its initial conditions. Next, we apply this index to a variant of the graded autocatalysis replication domain (GARD) model, Segre et al. (P Natl Acad Sci USA 97(8):4112-4117, 2000; Markovitch and Lancet Artif Life 18(3), 2012), and use it to study--under a unified and concise prebiotic evolutionary framework--both a variety of initial conditions of the universe and the OEE of species that evolve from them.

Is There an Optimal Level of Open-Endedness in Prebiotic Evolution?

NASA Astrophysics Data System (ADS)

Markovitch, Omer; Sorek, Daniel; Lui, Leong Ting; Lancet, Doron; Krasnogor, Natalio

2012-10-01

In this paper we explore the question of whether there is an optimal set up for a putative prebiotic system leading to open-ended evolution (OEE) of the events unfolding within this system. We do so by proposing two key innovations. First, we introduce a new index that measures OEE as a function of the likelihood of events unfolding within a universe given its initial conditions. Next, we apply this index to a variant of the graded autocatalysis replication domain (GARD) model, Segre et al. (P Natl Acad Sci USA 97(8):4112-4117, 2000; Markovitch and Lancet Artif Life 18(3), 2012), and use it to study - under a unified and concise prebiotic evolutionary framework - both a variety of initial conditions of the universe and the OEE of species that evolve from them.

Crash Models for Advanced Automotive Batteries: A Review of the Current State of the Art

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, John A.; Allu, Srikanth; Gorti, Sarma B.

Safety is a critical aspect of lithium-ion (Li-ion) battery design. Impact/crash conditions can trigger a complex interplay of mechanical contact, heat generation and electrical discharge, which can result in adverse thermal events. The cause of these thermal events has been linked to internal contact between the opposite electrodes, i.e. internal short circuit. The severity of the outcome is influenced by the configuration of the internal short circuit and the battery state. Different loading conditions and battery states may lead to micro (soft) shorts where material burnout due to generated heat eliminates contact between the electrodes, or persistent (hard) shorts whichmore » can lead to more significant thermal events and potentially damage the entire battery system and beyond. Experimental characterization of individual battery components for the onset of internal shorts is limited, since it is impractical to canvas all possible variations in battery state of charge, operating conditions, and impact loading in a timely manner. This report provides a survey of modeling and simulation approaches and documents a project initiated and funded by DOT/NHTSA to improve modeling and simulation capabilities in order to design tests that provide leading indicators of failure in batteries. In this project, ORNL has demonstrated a computational infrastructure to conduct impact simulations of Li-ion batteries using models that resolve internal structures and electro-thermo-chemical and mechanical conditions. Initial comparisons to abuse experiments on cells and cell strings conducted at ORNL and Naval Surface Warfare Center (NSWC) at Carderock MD for parameter estimation and model validation have been performed. This research has provided insight into the mechanisms of deformation in batteries (both at cell and electrode level) and their relationship to the safety of batteries.« less

Developing and applying the adverse outcome pathway ...

EPA Pesticide Factsheets

To support a paradigm shift in regulatory toxicology testing and risk assessment, the Adverse Outcome Pathway (AOP) concept has recently been proposed. This concept is similar to that for Mode of Action (MOA), describing a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis to predict effects for structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed.A variety of cellular and molecular processes are known to be critical to normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of principles of the description and assessment of MOA and AOPs, examples of adverse out

Body-borne IED detection: NATO DAT#10 BELCOAST 09 demonstration results

NASA Astrophysics Data System (ADS)

Alexander, Naomi; Gómez, Ignacio; Ortega, Isabel; Fiore, Franco; Coman, Cristian

2010-04-01

Belgium leads the tenth initiative in the CNAD Programme of Work for the Defense Against Terrorism (PoW DAT), dealing with Critical Infrastructure Protection (CIP). The BELCOAST 09 event, comprising a series of technology demonstrations, was organized to tackle the need for an event that brings together the operational, armaments and technological communities in the field of CIP. A counter terrorism scenario has been created: Terrorist with body-borne IED approaching the entrance of an installation, and a millimeter-wave imager's ability to detect IEDs has been demonstrated. The results of this scenario-based demonstration are presented in this paper.

Application of a framework for extrapolating chemical effects ...

EPA Pesticide Factsheets

Cross-species extrapolation of toxicity data from limited surrogate test organisms to all wildlife with potential of chemical exposure remains a key challenge in ecological risk assessment. A number of factors affect extrapolation, including the chemical exposure, pharmacokinetics, life-stage, and pathway similarities/differences. Here we propose a framework using a tiered approach for species extrapolation that enables a transparent weight-of-evidence driven evaluation of pathway conservation (or lack thereof) in the context of adverse outcome pathways. Adverse outcome pathways describe the linkages from a molecular initiating event, defined as the chemical-biomolecule interaction, through subsequent key events leading to an adverse outcome of regulatory concern (e.g., mortality, reproductive dysfunction). Tier 1 of the extrapolation framework employs in silico evaluations of sequence and structural conservation of molecules (e.g., receptors, enzymes) associated with molecular initiating events or upstream key events. Such evaluations make use of available empirical and sequence data to assess taxonomic relevance. Tier 2 uses in vitro bioassays, such as enzyme inhibition/activation, competitive receptor binding, and transcriptional activation assays to explore functional conservation of pathways across taxa. Finally, Tier 3 provides a comparative analysis of in vivo responses between species utilizing well-established model organisms to assess departure from

Effect on hospital-wide sedation practices after implementation of the 2001 JCAHO procedural sedation and analgesia guidelines.

PubMed

Pitetti, Raymond; Davis, Peter J; Redlinger, Robert; White, Jean; Wiener, Eugene; Calhoun, Karen H

2006-02-01

To describe the effect of implementing the Joint Commission on Accreditation of Healthcare Organization's guidelines for procedural sedation and analgesia (PSA) on the frequency of adverse events occurring during sedation. Prospective, descriptive study. Urban, tertiary care children's hospital. Patients requiring PSA. A PSA committee and a standardized protocol for PSA were developed during a 6-month period. Institutional oversight was initiated to monitor practitioner compliance with the program. Data were abstracted from the sedation record. The change in incidence of adverse events during PSA during the study. The strength of the association was determined by computing the Pearson product moment correlation. A total of 14 386 patients received PSA between July 1, 2001, and June 30, 2004. During the study, 7.6% of patients had an adverse event, with the most common being hypoxemia (39.7% of all adverse events). A trend toward a decrease in the incidence of adverse events was found during the study (Pearson product moment correlation, -0.68; P<.001). Implementation of the 2001 Joint Commission on Accreditation of Healthcare Organizations guidelines for the provision of PSA appeared to lead to a decrease in the incidence of adverse events during the study. Implementation of uniform standards of monitoring and care for the provision of PSA may lead to safer conditions for pediatric patients undergoing PSA.

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage.

PubMed

Kubiak, Jeffrey M; Culyba, Matthew J; Liu, Monica Yun; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

2017-11-17

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway.

Analysis of Lower Body Kinematic and Kinetic: Differences Between Age and Handicap in Golfers of Various Ages and Skill Levels

NASA Astrophysics Data System (ADS)

Smilensky, Alexander

The purpose of this thesis was to provide a preliminary analysis of lower body golf swing biomechanics. Fourteen golfers of various ages and handicaps performed 10 swings off a tee with their driver. This study focused on a number of dependent variables including lead knee joint flexion angles, internal/external rotations, valgus/varus angles, as well as ground reaction forces normalized to body weight (%BW), X-Factor angle and club head velocity. Dependent variables were analyzed at four specifically defined events (start, initiation of downswing, contact and swing termination). Simple linear regressions were performed using age and handicap as independent variables to see if patterns could be determined at any of the events. No significant trends or results were reported within our sample. An analysis of variance (ANOVA) was then used to examine the effect of event on specific dependent variables. A number of differences were reported within each of the variables across the four events. This study hoped to provide a more comprehensive understanding of the movement patterns occurring at the lower body with special focus on the lead knee.

Assessment of Critical Events Corridors through Multivariate Cascading Outages Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makarov, Yuri V.; Samaan, Nader A.; Diao, Ruisheng

2011-10-17

Massive blackouts of electrical power systems in North America over the past decade has focused increasing attention upon ways to identify and simulate network events that may potentially lead to widespread network collapse. This paper summarizes a method to simulate power-system vulnerability to cascading failures to a supplied set of initiating events synonymously termed as Extreme Events. The implemented simulation method is currently confined to simulating steady state power-system response to a set of extreme events. The outlined method of simulation is meant to augment and provide a new insight into bulk power transmission network planning that at present remainsmore » mainly confined to maintaining power system security for single and double component outages under a number of projected future network operating conditions. Although one of the aims of this paper is to demonstrate the feasibility of simulating network vulnerability to cascading outages, a more important goal has been to determine vulnerable parts of the network that may potentially be strengthened in practice so as to mitigate system susceptibility to cascading failures. This paper proposes to demonstrate a systematic approach to analyze extreme events and identify vulnerable system elements that may be contributing to cascading outages. The hypothesis of critical events corridors is proposed to represent repeating sequential outages that can occur in the system for multiple initiating events. The new concept helps to identify system reinforcements that planners could engineer in order to 'break' the critical events sequences and therefore lessen the likelihood of cascading outages. This hypothesis has been successfully validated with a California power system model.« less

Extreme precipitation forecasting in the Chilean Andean region with complex topography using the Weather Research and Forecasting (WRF) model

NASA Astrophysics Data System (ADS)

Gironás, J.; Yáñez Morroni, G.; Caneo, M.; Delgado, R.

2017-12-01

The Weather Research and Forecasting (WRF) model is broadly used for weather forecasting, hindcasting and researching due to its good performance. However, the atmospheric conditions for simulating are not always optimal when it includes complex topographies: affecting WRF mathematical stability and convergence, therefore, its performance. As Chile is a country strongly characterized by a complex topography and high gradients of elevation, WRF is ineffective resolving Chilean mountainous terrain and foothills. The need to own an effective weather forecasting tool relies on that Chile's main cities are located in these regions. Furthermore, the most intense rainfall events take place here, commonly caused by the presence of cutoff lows. This work analyzes a microphysics scheme ensemble to enhance initial forecasts made by the Chilean Weather Agency (DMC). These forecasts were made over the Santiago piedmont, in Quebrada de Ramón watershed, located upstream an urban area highly populated. In this region a non-existing planning increases the potential damage of a flash flood. An initial testing was made over different vertical levels resolution (39 and 50 levels), and subsequently testing with land use and surface models, and finally with the initial and boundary condition data (GFS/FNL). Our task made emphasis in analyzing microphysics and lead time (3 to 5 days before the storm peak) in the computational simulations over three extreme rainfall events between 2015 and 2017. WRF shortcoming are also related to the complex configuration of the synoptic events, even when the steep topography difficult the rainfall event peak amount, and to a lesser degree, the exact rainfall event beginning prediction. No evident trend was found in the lead time, but as expected, better results in rainfall and zero isotherm height are obtained with smaller anticipation. We found that WRF do predict properly the N-hours with the biggest amount of rainfall (5 hours corresponding to Quebrada de Ramón's time of concentration) and the temperatures during the event. This is a fundamental input to a hydrological model that could forecast flash floods. Finally, WSM-6Class microphysics was chosen as the one with best performance, but a geostatistical approach to countervail WRF forecasts' shortcomings over Andean piedmont is required.

High-Multiplicity Lead-Lead Interactions at 158 GeV/c per nucleon

NASA Technical Reports Server (NTRS)

Deines-Jones, P.; Cherry, M. L.; Dabrowska, A.; Holynski, R.; Jones, W. V.; Kolganova, E. D.; Kudzia, D.; Nilsen, B. S.; Olszewski, A.; Pozharova, E. A.;

The chemistry side of AOP: implications for toxicity ...

EPA Pesticide Factsheets

An adverse outcome pathway (AOP) is a structured representation of the biological events that lead to adverse impacts following a molecular initiating event caused by chemical interaction with a macromolecule. AOPs have been proposed to facilitate toxicity extrapolation across species through understanding of species similarity in the sequence of molecular, cellular, organ and organismal level responses. However, AOPs are non-specific regarding the identity of the chemical initiators, and the range of structures for which an AOP is considered applicable has generally been poorly defined. Applicability domain has been widely understood in the field of QSAR as the response and chemical structure space in which the model makes predictions with a given reliability, and has been traditionally applied to define the similarity of query molecules within the training set. Three dimensional (3D) receptor modeling offers an approach to better define the applicability domain for selected AOPs through determination of the chemical space of the molecular initiating event. Universal 3D-QSAR models were developed for acetylcholinesterase inhibitors and estrogen receptor agonists and antagonists using a combination of fingerprint, molecular docking and structure-based pharmacophore approaches. The models were based on the critical molecular interactions within each receptor ligand binding domain, and included the key amino acid residues responsible for high binding affinity. T

Sedimentary record of the 1872 earthquake and "Tsunami" at Owens Lake, southeast California

USGS Publications Warehouse

Smoot, J.P.; Litwin, R.J.; Bischoff, J.L.; Lund, S.J.

2000-01-01

In 1872, a magnitude 7.5-7.7 earthquake vertically offset the Owens Valley fault by more than a meter. An eyewitness reported a large wave on the surface of Owens Lake, presumably initiated by the earthquake. Physical evidence of this event is found in cores and trenches from Owens Lake, including soft-sediment deformation and fault offsets. A graded pebbly sand truncates these features, possibly over most of the lake floor, reflecting the "tsunami" wave. Confirmation of the timing of the event is provided by abnormally high lead concentrations in the sediment immediately above and below these proposed earthquake deposits derived from lead-smelting plants that operated near the eastern lake margin from 1869-1876. The bottom velocity in the deepest part of the lake needed to transport the coarsest grain sizes in the graded pebbly sand provides an estimate of the minimum initial 'tsunami' wave height at 37 cm. This is less than the wave height calculated from long-wave numerical models (about 55 cm) using average fault displacement during the earthquake. Two other graded sand deposits associated with soft-sediment deformation in the Owens Lake record are less than 3000 years old, and are interpreted as evidence of older earthquake and tsunami events. Offsets of the Owens Valley fault elsewhere in the valley indicate that at least two additional large earthquakes occurred during the Holocene, which is consistent with our observations in this lacustrine record.

European economies in crisis: A multifractal analysis of disruptive economic events and the effects of financial assistance

NASA Astrophysics Data System (ADS)

Siokis, Fotios M.

2014-02-01

We analyze the complexity of rare economic events in troubled European economies. The economic crisis initiated at the end of 2009, forced a number of European economies to request financial assistance from world organizations. By employing the stock market index as a leading indicator of the economic activity, we test whether the financial assistance programs altered the statistical properties of the index. The effects of major financial program agreements on the economies can be best illustrated by the comparison of the multifractal spectra of the time series before and after the agreement. We reveal that the returns of the time series exhibit strong multifractal properties for all periods under investigation. In two of the three investigated economies, financial assistance along with governments’ initiatives appear to have altered the statistical properties of the stock market indexes increasing the width of the multifractal spectra and thus the complexity of the market.

Beginning Teachers Reflect on Inclusive Practices--"I Didn't Realize That He Only Had Half a Hand"

ERIC Educational Resources Information Center

Hamilton, Carol; Kecskemeti, Maria

2015-01-01

Learning to value difference and diversity is a central goal of Initial Teacher Education (ITE) professional practice programmes in New Zealand. Yet the authors have continued to struggle to work with their ITE students to move them as a group towards such valuing in both theory and practice. In this article events that lead up to the changes…

Importance of correlations and fluctuations on the initial source eccentricity in high-energy nucleus-nucleus collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alver, B.; Ballintijn, M.; Busza, W.

2008-01-15

In relativistic heavy-ion collisions, anisotropic collective flow is driven, event by event, by the initial eccentricity of the matter created in the nuclear overlap zone. Interpretation of the anisotropic flow data thus requires a detailed understanding of the effective initial source eccentricity of the event sample. In this paper, we investigate various ways of defining this effective eccentricity using the Monte Carlo Glauber (MCG) approach. In particular, we examine the participant eccentricity, which quantifies the eccentricity of the initial source shape by the major axes of the ellipse formed by the interaction points of the participating nucleons. We show thatmore » reasonable variation of the density parameters in the Glauber calculation, as well as variations in how matter production is modeled, do not significantly modify the already established behavior of the participant eccentricity as a function of collision centrality. Focusing on event-by-event fluctuations and correlations of the distributions of participating nucleons, we demonstrate that, depending on the achieved event-plane resolution, fluctuations in the elliptic flow magnitude v{sub 2} lead to most measurements being sensitive to the root-mean-square rather than the mean of the v{sub 2} distribution. Neglecting correlations among participants, we derive analytical expressions for the participant eccentricity cumulants as a function of the number of participating nucleons, N{sub part}, keeping nonnegligible contributions up to O(1/N{sub part}{sup 3}). We find that the derived expressions yield the same results as obtained from mixed-event MCG calculations which remove the correlations stemming from the nuclear collision process. Most importantly, we conclude from the comparison with MCG calculations that the fourth-order participant eccentricity cumulant does not approach the spatial anisotropy obtained assuming a smooth nuclear matter distribution. In particular, for the Cu+Cu system, these quantities deviate from each other by almost a factor of 2 over a wide range in centrality. This deviation reflects the essential role of participant spatial correlations in the interaction of two nuclei.« less

Practice-Based Evidence Informs Environmental Health Policy and Regulation: A Case Study of Residential Lead-Soil Contamination in Rhode Island

PubMed Central

Thompson, Marcella Remer; Burdon, Andrea; Boekelheide, Kim

2013-01-01

Prior to 1978, the exteriors of Rhode Island's municipal water towers were painted with lead-containing paint. Over time, this lead-containing paint either flaked-off or was mechanically removed and deposited on adjacent residential properties. Residents challenged inconsistencies across state agencies and federal requirements for collecting and analyzing soil samples. The purpose of this case study was to evaluate the efficacy of Rhode Island Department of Health (RIDOH) soil sampling regulations in determining the extent of lead contamination on residential properties using real world data. Researchers interviewed key government personnel, reviewed written accounts of events and regulations, and extracted and compiled lead data from environmental soil sampling on 31 residential properties adjacent to six municipal water towers. Data were available for 498 core samples. Approximately 26% of the residential properties had lead soil concentrations >1,000 mg/kg. Overall, lead concentration was inversely related to distance from the water tower. Analysis indicated that surface samples alone were insufficient to classify a property as “lead safe”. Potential for misclassification using RIDOH regulations was 13%. For properties deemed initially “lead free”, the total number of samples was too few to analyze. Post-remediation lead-soil concentrations suggest the extent of lead contamination may have been deeper than initially determined. Additional data would improve the ability to draw more meaningful and generalized conclusions. Inconsistencies among regulatory agencies responsible for environmental health obfuscate transparency and erode the public's trust in the regulatory process. Recommendations for improvement include congruency across departmental regulations and specific modifications to soil sampling regulations reflective of lowered CDC reference blood lead value for children 1 to 5 years old (5μg/dL). While scientific research informed the initial development of these environmental health policies and regulations, practice-based evidence did not support their efficacy in context of real world practice. PMID:24055667

Convective forcing of mercury and ozone in the Arctic boundary layer induced by leads in sea ice.

PubMed

Moore, Christopher W; Obrist, Daniel; Steffen, Alexandra; Staebler, Ralf M; Douglas, Thomas A; Richter, Andreas; Nghiem, Son V

2014-02-06

The ongoing regime shift of Arctic sea ice from perennial to seasonal ice is associated with more dynamic patterns of opening and closing sea-ice leads (large transient channels of open water in the ice), which may affect atmospheric and biogeochemical cycles in the Arctic. Mercury and ozone are rapidly removed from the atmospheric boundary layer during depletion events in the Arctic, caused by destruction of ozone along with oxidation of gaseous elemental mercury (Hg(0)) to oxidized mercury (Hg(II)) in the atmosphere and its subsequent deposition to snow and ice. Ozone depletion events can change the oxidative capacity of the air by affecting atmospheric hydroxyl radical chemistry, whereas atmospheric mercury depletion events can increase the deposition of mercury to the Arctic, some of which can enter ecosystems during snowmelt. Here we present near-surface measurements of atmospheric mercury and ozone from two Arctic field campaigns near Barrow, Alaska. We find that coastal depletion events are directly linked to sea-ice dynamics. A consolidated ice cover facilitates the depletion of Hg(0) and ozone, but these immediately recover to near-background concentrations in the upwind presence of open sea-ice leads. We attribute the rapid recoveries of Hg(0) and ozone to lead-initiated shallow convection in the stable Arctic boundary layer, which mixes Hg(0) and ozone from undepleted air masses aloft. This convective forcing provides additional Hg(0) to the surface layer at a time of active depletion chemistry, where it is subject to renewed oxidation. Future work will need to establish the degree to which large-scale changes in sea-ice dynamics across the Arctic alter ozone chemistry and mercury deposition in fragile Arctic ecosystems.

Moving the Barricades to Physical Activity: A Qualitative Analysis of Open Streets Initiatives Across the United States.

PubMed

Eyler, Amy A; Hipp, J Aaron; Lokuta, Julie

2015-01-01

Ciclovía, or Open Streets initiatives, are events where streets are opened for physical activity and closed to motorized traffic. Although the initiatives are gaining popularity in the United States, little is known about planning and implementing them. The goals of this paper are to explore the development and implementation of Open Streets initiatives and make recommendations for increasing the capacity of organizers to enhance initiative success. Phenomenology with qualitative analysis of structured interviews was used. Study setting was urban and suburban communities in the United States. Study participants were organizers of Open Streets initiatives in U.S. cities. Using a list of 47 events held in 2011, 27 lead organizers were interviewed by telephone about planning, implementation, and lessons learned. The interviews were digitally recorded and transcribed. A phenomenologic approach was used, an initial coding tool was developed after reviewing a sample of transcripts, and constant comparative coding methodology was applied. Themes and subthemes were generated from codes. The most common reasons for initiation were to highlight or improve health and transportation. Most initiatives aimed to reach the general population, but some targeted families, children, or specific neighborhoods. Getting people to understand the concept of Open Streets was an important challenge. Other challenges included lack of funding and personnel, and complex logistics. These initiatives democratize public space for citizens while promoting physical activity, social connectedness, and other broad agendas. There are opportunities for the research community to contribute to the expanse and sustainability of Open Streets, particularly in evaluation and dissemination.

A Process Study of the Development of Virtual Research Environments

NASA Astrophysics Data System (ADS)

Ahmed, I.; Cooper, K.; McGrath, R.; Griego, G.; Poole, M. S.; Hanisch, R. J.

2014-05-01

In recent years, cyberinfrastructures have been deployed to create virtual research environments (VREs) - such as the Virtual Astronomical Observatory (VAO) - to enhance the quality and speed of scientific research, and to foster global scientific communities. Our study utilizes process methodology to study the evolution of VREs. This approach focuses on a series of events that bring about or lead to some outcome, and attempts to specify the generative mechanism that could produce the event series. This paper briefly outlines our approach and describes initial results of a case study of the VAO, one of the participating VREs. The case study is based on interviews with seven individuals participating in the VAO, and analysis of project documents and online resources. These sources are hand tagged to identify events related to the thematic tracks, to yield a narrative of the project. Results demonstrate the event series of an organization through traditional methods augmented by virtual sources.

Visualizing Tensions in an Ethnographic Moment: Images and Intersubjectivity.

PubMed

Crowder, Jerome W

2017-01-01

Images function as sources of data and influence our thinking about fieldwork, representation, and intersubjectivity. In this article, I show how both the ethnographic relationships and the working method of photography lead to a more nuanced understanding of a healing event. I systematically analyze 33 photographs made over a 15-minute period during the preparation and application of a poultice (topical cure) in a rural Andean home. The images chronicle the event, revealing my initial reaction and the decisions I made when tripping the shutter. By unpacking the relationship between ethnographer and subject, I reveal the constant negotiation of positions, assumptions, and expectations that make up intersubjectivity. For transparency, I provide thumbnails of all images, including metadata, so that readers may consider alternative interpretations of the images and event.

A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage

PubMed Central

2017-01-01

The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway. PMID:28826208

Outcomes of cardiac pacing in adult patients after a Fontan operation.

PubMed

Egbe, Alexander C; Huntley, Geoffery D; Connolly, Heidi M; Ammash, Naser M; Deshmukh, Abhishek J; Khan, Arooj R; Said, Sameh M; Akintoye, Emmanuel; Warnes, Carole A; Kapa, Suraj

2017-12-01

Cardiac pacing can be challenging after a Fontan operation, and limited data exist regarding pacing in adult Fontan patients. The objectives of our study were to determine risk factors for pacing and occurrence of device-related complications (DRCs) and pacemaker reinterventions. We performed a retrospective review of Fontan patients from 1994 through 2014. We defined DRCs as lead failure, lead recall, cardiac perforation, lead thrombus/vegetation, or device-related infection, and cardiovascular adverse events (CAEs) as venous thrombosis, stroke, death, or heart transplant. Pacemaker reintervention was defined as lead failure or recall. Of 439 patients, 166 (38%) had pacemakers implanted (79 during childhood; 87, adulthood); 114 patients (69%) received epicardial leads initially, and 52 (31%), endocardial leads. Pacing was initially atrial in 52 patients (31%); ventricular, 30 (18%); or dual chamber, 84 (51%). There were 37 reinterventions (1.9% per year) and 48 DRCs (2.4% per year). Pacemaker implantation during childhood was a risk factor for DRCs (hazard ratio, 2.01 [CI, 1.22-5.63]; P = .03). There were 70 CAEs (venous thrombosis, 5; stroke, 11; transplant, 8; and death, 46), yielding a rate of 3.5% per year. DRCs, CAEs, and reintervention rates were comparable for patients with epicardial or endocardial leads. More than one-third of adult Fontan patients referred to Mayo Clinic had pacemaker implantation. Epicardial leads were associated with high rate of pacemaker reinterventions but similar DRC rates in comparison to endocardial leads. Copyright © 2017 Elsevier Inc. All rights reserved.

Ideal hydrodynamics and elliptic flow at CERN Super Proton Synchrotron (SPS) energies: Importance of the initial conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petersen, Hannah; Institut fuer Theoretische Physik, Johann Wolfgang Goethe-Universitaet, Max-von-Laue-Str. 1, D-60438 Frankfurt am Main; Bleicher, Marcus

2009-05-15

The elliptic flow excitation function calculated in a full (3+1) dimensional hybrid Boltzmann approach with an intermediate hydrodynamic stage for heavy ion reactions from GSI Schwerionen Synchrotron to the highest CERN Super Proton Synchrotron (SPS) energies is discussed in the context of the experimental data. In this study, we employ a hadron gas equation of state to investigate the differences in the dynamics and viscosity effects. The specific event-by-event setup with initial conditions and freeze-out from a nonequilibrium transport model allows for a direct comparison between ideal fluid dynamics and transport simulations. At higher SPS energies, where the pure transportmore » calculation cannot account for the high elliptic flow values, the smaller mean free path in the hydrodynamic evolution leads to higher elliptic flow values. In contrast to previous studies within pure hydrodynamics, the more realistic initial conditions employed here and the inclusion of a sequential final state hadronic decoupling provides results that are in line with the experimental data almost over the whole energy range from E{sub lab}=2-160A GeV. Thus, this new approach leads to a substantially different shape of the v{sub 2}/{epsilon} scaling curve as a function of (1/SdN{sub ch}/dy) in line with the experimental data compared to previous ideal hydrodynamic calculations. This hints at a strong influence of the initial conditions for the hydrodynamic evolution on the finally observed v{sub 2} values, thus questioning the standard interpretation that the hydrodynamic limit is only reached at BNL Relativistic Heavy Ion Collider energies.« less

Data normalization in biosurveillance: an information-theoretic approach.

PubMed

Peter, William; Najmi, Amir H; Burkom, Howard

2007-10-11

An approach to identifying public health threats by characterizing syndromic surveillance data in terms of its surprisability is discussed. Surprisability in our model is measured by assigning a probability distribution to a time series, and then calculating its entropy, leading to a straightforward designation of an alert. Initial application of our method is to investigate the applicability of using suitably-normalized syndromic counts (i.e., proportions) to improve early event detection.

KENNEDY SPACE CENTER, FLA. - NASA’s Ed Weiler, associate administrator for Space Science, speaks to employees and guests during the rollout at KSC of the Agency initiative One NASA . The event was held at the IMAX Theater®. Explaining how their respective centers contribute to One NASA, along with Weiler, were KSC Director Jim Kennedy; James Jennings, NASA’s associate deputy administrator for institutions and asset management; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

NASA Image and Video Library

2003-08-20

KENNEDY SPACE CENTER, FLA. - NASA’s Ed Weiler, associate administrator for Space Science, speaks to employees and guests during the rollout at KSC of the Agency initiative One NASA . The event was held at the IMAX Theater®. Explaining how their respective centers contribute to One NASA, along with Weiler, were KSC Director Jim Kennedy; James Jennings, NASA’s associate deputy administrator for institutions and asset management; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

Biophysical Approaches for Oral Wound Healing: Emphasis on Photobiomodulation

PubMed Central

Khan, Imran; Arany, Praveen

2015-01-01

Significance: Oral wounds can lead to significant pain and discomfort as well as affect overall general health due to poor diet and inadequate nutrition. Besides many biological and pharmaceutical methods being investigated, there is growing interest in exploring various biophysical devices that utilize electric, magnetic, ultrasound, pressure, and light energy. Recent Advances: Significant insight into mechanisms of these biophysical devices could provide a clear rationale for their clinical use. Preclinical studies are essential precursors in determining physiological mechanisms and elucidation of causal pathways. This will lead to development of safe and effective therapeutic protocols for clinical wound management. Critical Issues: Identification of precise events initiated by biophysical devices, specifically photobiomodulation—the major focus of this review, offers promising avenues in improving oral wound management. The primary phase responses initiated by the interventions that distinctly contribute to the therapeutic response must be clearly delineated from secondary phase responses. The latter events are a consequence of the wound healing process and must not be confused with causal mechanisms. Future Direction: Clinical adoption of these biophysical devices needs robust and efficacious protocols that can be developed by well-designed preclinical and clinical studies. Elucidation of the precise molecular mechanisms of these biophysical approaches could determine optimization of their applications for predictive oral wound care. PMID:26634185

Analysis of arrhythmic events is useful to detect lead failure earlier in patients followed by remote monitoring.

PubMed

Nishii, Nobuhiro; Miyoshi, Akihito; Kubo, Motoki; Miyamoto, Masakazu; Morimoto, Yoshimasa; Kawada, Satoshi; Nakagawa, Koji; Watanabe, Atsuyuki; Nakamura, Kazufumi; Morita, Hiroshi; Ito, Hiroshi

2018-03-01

Remote monitoring (RM) has been advocated as the new standard of care for patients with cardiovascular implantable electronic devices (CIEDs). RM has allowed the early detection of adverse clinical events, such as arrhythmia, lead failure, and battery depletion. However, lead failure was often identified only by arrhythmic events, but not impedance abnormalities. To compare the usefulness of arrhythmic events with conventional impedance abnormalities for identifying lead failure in CIED patients followed by RM. CIED patients in 12 hospitals have been followed by the RM center in Okayama University Hospital. All transmitted data have been analyzed and summarized. From April 2009 to March 2016, 1,873 patients have been followed by the RM center. During the mean follow-up period of 775 days, 42 lead failure events (atrial lead 22, right ventricular pacemaker lead 5, implantable cardioverter defibrillator [ICD] lead 15) were detected. The proportion of lead failures detected only by arrhythmic events, which were not detected by conventional impedance abnormalities, was significantly higher than that detected by impedance abnormalities (arrhythmic event 76.2%, 95% CI: 60.5-87.9%; impedance abnormalities 23.8%, 95% CI: 12.1-39.5%). Twenty-seven events (64.7%) were detected without any alert. Of 15 patients with ICD lead failure, none has experienced inappropriate therapy. RM can detect lead failure earlier, before clinical adverse events. However, CIEDs often diagnose lead failure as just arrhythmic events without any warning. Thus, to detect lead failure earlier, careful human analysis of arrhythmic events is useful. © 2017 Wiley Periodicals, Inc.

Master Logic Diagram: An Approach to Identify Initiating Events of HTGRs

NASA Astrophysics Data System (ADS)

Purba, J. H.

2018-02-01

Initiating events of a nuclear power plant being evaluated need to be firstly identified prior to applying probabilistic safety assessment on that plant. Various types of master logic diagrams (MLDs) have been proposedforsearching initiating events of the next generation of nuclear power plants, which have limited data and operating experiences. Those MLDs are different in the number of steps or levels and different in the basis for developing them. This study proposed another type of MLD approach to find high temperature gas cooled reactor (HTGR) initiating events. It consists of five functional steps starting from the top event representing the final objective of the safety functions to the basic event representing the goal of the MLD development, which is an initiating event. The application of the proposed approach to search for two HTGR initiating events, i.e. power turbine generator trip and loss of offsite power, is provided. The results confirmed that the proposed MLD is feasiblefor finding HTGR initiating events.

Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors.

PubMed

Hernández-Saavedra, Diego; Strakovsky, Rita S; Ostrosky-Wegman, Patricia; Pan, Yuan-Xiang

2017-11-01

The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy. © 2017 American Society for Nutrition.

Ensemble-based flash-flood modelling: Taking into account hydrodynamic parameters and initial soil moisture uncertainties

NASA Astrophysics Data System (ADS)

Edouard, Simon; Vincendon, Béatrice; Ducrocq, Véronique

2018-05-01

Intense precipitation events in the Mediterranean often lead to devastating flash floods (FF). FF modelling is affected by several kinds of uncertainties and Hydrological Ensemble Prediction Systems (HEPS) are designed to take those uncertainties into account. The major source of uncertainty comes from rainfall forcing and convective-scale meteorological ensemble prediction systems can manage it for forecasting purpose. But other sources are related to the hydrological modelling part of the HEPS. This study focuses on the uncertainties arising from the hydrological model parameters and initial soil moisture with aim to design an ensemble-based version of an hydrological model dedicated to Mediterranean fast responding rivers simulations, the ISBA-TOP coupled system. The first step consists in identifying the parameters that have the strongest influence on FF simulations by assuming perfect precipitation. A sensitivity study is carried out first using a synthetic framework and then for several real events and several catchments. Perturbation methods varying the most sensitive parameters as well as initial soil moisture allow designing an ensemble-based version of ISBA-TOP. The first results of this system on some real events are presented. The direct perspective of this work will be to drive this ensemble-based version with the members of a convective-scale meteorological ensemble prediction system to design a complete HEPS for FF forecasting.

How the toughness in metallic glasses depends on topological and chemical heterogeneity

PubMed Central

An, Qi; Samwer, Konrad; Demetriou, Marios D.; Floyd, Michael C.; Duggins, Danielle O.; Johnson, William L.; Goddard, William A.

2016-01-01

To gain insight into the large toughness variability observed between metallic glasses (MGs), we examine the origin of fracture toughness through bending experiments and molecular dynamics (MD) simulations for two binary MGs: Pd82Si18 and Cu46Zr54. The bending experiments show that Pd82Si18 is considerably tougher than Cu46Zr54, and the higher toughness of Pd82Si18 is attributed to an ability to deform plastically in the absence of crack nucleation through cavitation. The MD simulations study the initial stages of cavitation in both materials and extract the critical factors controlling cavitation. We find that for the tougher Pd82Si18, cavitation is governed by chemical inhomogeneity in addition to topological structures. In contrast, no such chemical correlations are observed in the more brittle Cu46Zr54, where topological low coordination number polyhedra are still observed around the critical cavity. As such, chemical inhomogeneity leads to more difficult cavitation initiation in Pd82Si18 than in Cu46Zr54, leading to a higher toughness. The absence of chemical separation during cavitation initiation in Cu46Zr54 decreases the energy barrier for a cavitation event, leading to lower toughness. PMID:27307438

Hydrodynamic Flow Fluctuations in √sNN = 5:02 TeV PbPbCollisions

NASA Astrophysics Data System (ADS)

Castle, James R.

The collective, anisotropic expansion of the medium created in ultrarelativistic heavy-ion collisions, known as flow, is characterized through a Fourier expansion of the final-state azimuthal particle density. In the Fourier expansion, flow harmonic coefficients vn correspond to shape components in the final-state particle density, which are a consequence of similar spatial anisotropies in the initial-state transverse energy density of a collision. Flow harmonic fluctuations are studied for PbPb collisions at √sNN = 5.02 TeV using the CMS detector at the CERN LHC. Flow harmonic probability distributions p( vn) are obtained using particles with 0.3 < pT < 3.0 GeV/c and ∥eta∥ < 1.0 by removing finite-multiplicity resolution effects from the observed azimuthal particle density through an unfolding procedure. Cumulant elliptic flow harmonics (n = 2) are determined from the moments of the unfolded p(v2) distributions and used to construct observables in 5% wide centrality bins up to 60% that relate to the initial-state spatial anisotropy. Hydrodynamic models predict that fluctuations in the initial-state transverse energy density will lead to a non-Gaussian component in the elliptic flow probability distributions that manifests as a negative skewness. A statistically significant negative skewness is observed for all centrality bins as evidenced by a splitting between the higher-order cumulant elliptic flow harmonics. The unfolded p (v2) distributions are transformed assuming a linear relationship between the initial-state spatial anisotropy and final-state flow and are fitted with elliptic power law and Bessel Gaussian parametrizations to infer information on the nature of initial-state fluctuations. The elliptic power law parametrization is found to provide a more accurate description of the fluctuations than the Bessel-Gaussian parametrization. In addition, the event-shape engineering technique, where events are further divided into classes based on an observed ellipticity, is used to study fluctuation-driven differences in the initial-state spatial anisotropy for a given collision centrality that would otherwise be destroyed by event-averaging techniques. Correlations between the first and second moments of p( vn) distributions and event ellipticity are measured for harmonic orders n = 2 - 4 by coupling event-shape engineering to the unfolding technique.

Seasonal Climate Predictability in a Coupled OAGCM Using a Different Approach for Ensemble Forecasts.

NASA Astrophysics Data System (ADS)

Luo, Jing-Jia; Masson, Sebastien; Behera, Swadhin; Shingu, Satoru; Yamagata, Toshio

2005-11-01

Predictabilities of tropical climate signals are investigated using a relatively high resolution Scale Interaction Experiment Frontier Research Center for Global Change (FRCGC) coupled GCM (SINTEX-F). Five ensemble forecast members are generated by perturbing the model’s coupling physics, which accounts for the uncertainties of both initial conditions and model physics. Because of the model’s good performance in simulating the climatology and ENSO in the tropical Pacific, a simple coupled SST-nudging scheme generates realistic thermocline and surface wind variations in the equatorial Pacific. Several westerly and easterly wind bursts in the western Pacific are also captured.Hindcast results for the period 1982 2001 show a high predictability of ENSO. All past El Niño and La Niña events, including the strongest 1997/98 warm episode, are successfully predicted with the anomaly correlation coefficient (ACC) skill scores above 0.7 at the 12-month lead time. The predicted signals of some particular events, however, become weak with a delay in the phase at mid and long lead times. This is found to be related to the intraseasonal wind bursts that are unpredicted beyond a few months of lead time. The model forecasts also show a “spring prediction barrier” similar to that in observations. Spatial SST anomalies, teleconnection, and global drought/flood during three different phases of ENSO are successfully predicted at 9 12-month lead times.In the tropical North Atlantic and southwestern Indian Ocean, where ENSO has predominant influences, the model shows skillful predictions at the 7 12-month lead times. The distinct signal of the Indian Ocean dipole (IOD) event in 1994 is predicted at the 6-month lead time. SST anomalies near the western coast of Australia are also predicted beyond the 12-month lead time because of pronounced decadal signals there.

Prediction and Predictability of the Madden Julian Oscillation in the NASA GEOS-5 Seasonal-to-Subseasonal System

NASA Technical Reports Server (NTRS)

Achuthavarier, Deepthi; Koster, Randal; Marshak, Jelena; Schubert, Siegfried; Molod, Andrea

2018-01-01

In this study, we examine the prediction skill and predictability of the Madden Julian Oscillation (MJO) in a recent version of the NASA GEOS-5 atmosphere-ocean coupled model run at at 1/2 degree horizontal resolution. The results are based on a suite of hindcasts produced as part of the NOAA SubX project, consisting of seven ensemble members initialized every 5 days for the period 1999-2015. The atmospheric initial conditions were taken from the Modern-Era Retrospective analysis for Research and Applications, Version 2 (MERRA-2), and the ocean and the sea ice were taken from a GMAO ocean analysis. The land states were initialized from the MERRA-2 land output, which is based on observation-corrected precipitation fields. We investigated the MJO prediction skill in terms of the bivariate correlation coefficient for the real-time multivariate MJO (RMM) indices. The correlation coefficient stays at or above 0.5 out to forecast lead times of 26-36 days, with a pronounced increase in skill for forecasts initialized from phase 3, when the MJO convective anomaly is located in the central tropical Indian Ocean. A corresponding estimate of the upper limit of the predictability is calculated by considering a single ensemble member as the truth and verifying the ensemble mean of the remaining members against that. The predictability estimates fall between 35-37 days (taken as forecast lead when the correlation reaches 0.5) and are rather insensitive to the initial MJO phase. The model shows slightly higher skill when the initial conditions contain strong MJO events compared to weak events, although the difference in skill is evident only from lead 1 to 20. Similar to other models, the RMM-index-based skill arises mostly from the circulation components of the index. The skill of the convective component of the index drops to 0.5 by day 20 as opposed to day 30 for circulation fields. The propagation of the MJO anomalies over the Maritime Continent does not appear problematic in the GEOS-5 hindcasts implying that the Maritime Continent predictability barrier may not be a major concern in this model. Finally, the MJO prediction skill in this version of GEOS-5 is superior to that of the current seasonal prediction system at the GMAO; this could be partly attributed to a slightly better representation of the MJO in the free running version of this model and partly to the improved atmospheric initialization from MERRA-2.

Beam Thrust Cross Section for Drell-Yan Production at Next-to-Next-to-Leading-Logarithmic Order

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, Iain W.; Tackmann, Frank J.; Waalewijn, Wouter J.

2011-01-21

At the LHC and Tevatron strong initial-state radiation (ISR) plays an important role. It can significantly affect the partonic luminosity available to the hard interaction or contaminate a signal with additional jets and soft radiation. An ideal process to study ISR is isolated Drell-Yan production, pp{yields}Xl{sup +}l{sup -} without central jets, where the jet veto is provided by the hadronic event shape beam thrust {tau}{sub B}. Most hadron collider event shapes are designed to study central jets. In contrast, requiring {tau}{sub B}<<1 provides an inclusive veto of central jets and measures the spectrum of ISR. For {tau}{sub B}<<1 we carrymore » out a resummation of {alpha}{sub s}{sup n}ln{sup m{tau}}{sub B} corrections at next-to-next-to-leading-logarithmic order. This is the first resummation at this order for a hadron-hadron collider event shape. Measurements of {tau}{sub B} at the Tevatron and LHC can provide crucial tests of our understanding of ISR and of {tau}{sub B}'s utility as a central jet veto.« less

Framework for Interpretation of Trypsin–antitrypsin Imbalance and Genetic Heterogeneity in Pancreatitis

PubMed Central

Lin, Kun; Gao, Feng; Chen, Qingquan; Liu, Qicai; Chen, Shu

2015-01-01

Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER), and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them. PMID:26228362

[Influence of cumulated sexual trauma on sexual life and relationship of a patient].

PubMed

Sobański, Jerzy A; Klasa, Katarzyna; Cyranka, Katarzyna; Müldner-Nieckowski, Lukasz; Dembińska, Edyta; Rutkowski, Krzysztof; Smiatek-Mazgaj, Bogna; Mielimaka, Michal

2014-01-01

The assessment of links of accumulated traumatic events of a sexual nature, recollected from the past, with the current functioning of the patients in the area of sexual life and relationship. Comorbidity of memories of traumatic sexual events from childhood and puberty in patients with the features of their current partner relationships and sexual life were analyzed on the basis of Live Inventory completed by 2,582 women and 1,347 men, before treatment in day hospital (years 1980-2002). The accumulation was evaluated for a combination of two or three selected events. The presence of relatively numerous traumatic events in the field of sexuality early initiation or enforced initiation, incest or its attempt, sub-optimal sexual education and punishment for masturbation was indicated. In some patients, these events occurred simultaneously. Especially in women, the presence in the same person of two or three aggravating circumstances of life was associated with a higher risk of among others fleeting, casual sexual contacts, marriage under the influence of environment pressures, reluctance to partner. Increased accumulation - the presence in the same patient of more than one adverse circumstances associated with sexual development - leads to a higher incidence of interference in relationship with a partner including the elements of sexual dysfunction. The obtained results are generally consistent with clinical observations and literature despite different, simplified methodology of the study based on the analysis of single variables from questionnaire interviews. Finding fewer links in the group of men can be explained by their much lower number in the study group and less frequent burdening with certain traumatic events or different experiencing.

Numerical modeling of coronal mass ejections based on various pre-event model atmospheres

NASA Technical Reports Server (NTRS)

Suess, S. T.; Wang, A. H.; Wu, S. T.; Poletto, G.

1994-01-01

We examine how the initial state (pre-event corona) affects the numerical MHD simulation for a coronal mass ejection (CME). Earlier simulations based on a pre-event corona with a homogeneous density and temperature distribution at lower boundary (i.e. solar surface) have been used to analyze the role of streamer properties in determining the characteristics of loop-like transients. The present paper extends these studies to show how a broader class of global coronal properties leads not only to different types of CME's, but also modifies the adjacent quiet corona and/or coronal holes. We consider four pre-event coronal cases: (1) Constant boundary conditions and a polytropic gas with gamma = 1.05; (2) Non-constant (latitude dependent) boundary conditions and a polytropic gas with gamma = 1.05; (3) Constant boundary conditions with a volumetric energy source and gamma = 1.67; (4) Non-constant (latitude dependent) boundary conditions with a volumetric energy source and gamma = 1.67. In all models, the pre-event magnetic fields separate the corona into closed field regions (streamers) and open field regions. The CME's initiation is simulated by introducing at the base of the corona, within the streamer region, a standard pressure pulse and velocity change. Boundary values are determined using MHD characteristic theory. The simulations show how different CME's, including loop-like transients, clouds, and bright rays, might occur. There are significant new features in comparison to published results. We conclude that the pre-event corona is a crucial factor in dictating CME's properties.

Numerical Modeling of Coronal Mass Ejections Based on Various Pre-event Model Atmospheres

NASA Technical Reports Server (NTRS)

Wang, A. H.; Wu, S. T.; Suess, S. T.; Poletto, G.

1995-01-01

We examine how the initial state (pre-event corona) affects the numerical MHD simulation for a coronal mass ejection (CME). Earlier simulations based on a pre-event corona with a homogeneous density and temperature distribution, at the lower boundary (i.e., solar surface) have been used to analyze the role of streamer properties in determining the characteristics of loop-like transients. The present paper extends these studies to show how a broader class of global coronal properties leads not only to different types of CME's, but also modifies the adjacent quiet corona and/or coronal holes. We consider four pre-event coronal cases: (1) constant boundary conditions and a polytropic gas with gamma = 1.05; (2) non-constant (latitude dependent) boundary conditions and a polytropic gas with gamma = 1.05; (3) constant boundary conditions with a volumetric energy source and gamma = 1.67; (4) non-constant (latitude dependent) boundary conditions with a volumetric energy source and gamma = 1.67. In all models, the pre-event magnetic fields separate the corona into closed field regions (streamers) and open field regions. The CME's initiation is simulated by introducing at the base of the corona, within the streamer region, a standard pressure pulse and velocity change. Boundary values are determined using magnetohydrodynamic (MHD) characteristic theory. The simulations show how different CME's, including loop-like transients, clouds and bright rays, might occur. There are significant new features in comparison to published results. We conclude that the pre-event corona is a crucial factor in dictating CME's properties.

A hydro-meteorological model chain to assess the influence of natural variability and impacts of climate change on extreme events and propose optimal water management

NASA Astrophysics Data System (ADS)

von Trentini, F.; Willkofer, F.; Wood, R. R.; Schmid, F. J.; Ludwig, R.

2017-12-01

The ClimEx project (Climate change and hydrological extreme events - risks and perspectives for water management in Bavaria and Québec) focuses on the effects of climate change on hydro-meteorological extreme events and their implications for water management in Bavaria and Québec. Therefore, a hydro-meteorological model chain is applied. It employs high performance computing capacity of the Leibniz Supercomputing Centre facility SuperMUC to dynamically downscale 50 members of the Global Circulation Model CanESM2 over European and Eastern North American domains using the Canadian Regional Climate Model (RCM) CRCM5. Over Europe, the unique single model ensemble is conjointly analyzed with the latest information provided through the CORDEX-initiative, to better assess the influence of natural climate variability and climatic change in the dynamics of extreme events. Furthermore, these 50 members of a single RCM will enhance extreme value statistics (extreme return periods) by exploiting the available 1500 model years for the reference period from 1981 to 2010. Hence, the RCM output is applied to drive the process based, fully distributed, and deterministic hydrological model WaSiM in high temporal (3h) and spatial (500m) resolution. WaSiM and the large ensemble are further used to derive a variety of hydro-meteorological patterns leading to severe flood events. A tool for virtual perfect prediction shall provide a combination of optimal lead time and management strategy to mitigate certain flood events following these patterns.

Taste receptors in the gastrointestinal tract. I. Bitter taste receptors and alpha-gustducin in the mammalian gut.

PubMed

Rozengurt, Enrique

2006-08-01

Molecular sensing by gastrointestinal (GI) cells plays a critical role in the control of multiple fundamental functions in digestion and also initiates hormonal and/or neural pathways leading to the regulation of caloric intake, pancreatic insulin secretion, and metabolism. Molecular sensing in the GI tract is also responsible for the detection of ingested harmful drugs and toxins, thereby initiating responses critical for survival. The initial recognition events and mechanism(s) involved remain incompletely understood. The notion to be discussed in this article is that there are important similarities between the chemosensory machinery elucidated in specialized neuroepithelial taste receptor cells of the lingual epithelium and the molecular transducers localized recently in enteroendocrine open GI cells that sense the chemical composition of the luminal contents of the gut.

ALTERNATE MECHANISMS OF INITIAL PATTERN RECOGNITION DRIVE DIFFERENTIAL IMMUNE RESPONSES TO RELATED POXVIRUSES

PubMed Central

O’Gorman, William E.; Sampath, Padma; Simonds, Erin F.; Sikorski, Rachel; O’Malley, Mark; Krutzik, Peter O.; Chen, Hannah; Panchanathan, Vijay; Chaudhri, Geeta; Karupiah, Gunasegaran; Lewis, David B.; Thorne, Steve H.; Nolan, Garry P.

2010-01-01

Summary Although vaccinia virus infection results in induction of a robust immunizing response, many closely related poxviruses such as variola (smallpox) and ectromelia (mousepox) are highly pathogenic in their natural hosts. We developed a strategy to map the activation of key signaling networks in vivo and applied this approach to define and compare the earliest signaling events elicited by poxvirus infections in mice. Vaccinia induced rapid TLR2-dependent responses leading to IL-6 production, which then initiated STAT3 signaling in dendritic cells and T cells. In contrast, ectromelia did not induce TLR2 activation and profound mouse strain-dependent responses were observed. In resistant C57BL/6 mice, the STAT1 and STAT3 pathways were rapidly activated, whereas in susceptible BALB/c mice, IL-6-dependent STAT3 activation did not occur. These results indicate that vaccination with vaccinia is dependent on rapid TLR2 and IL-6 driven responses and link the earliest immune signaling events to the outcome of infection. PMID:20709294

Reactive simulation of the chemistry behind the condensed-phase ignition of RDX from hot spots.

PubMed

Joshi, Kaushik L; Chaudhuri, Santanu

2015-07-28

Chemical events that lead to thermal initiation and spontaneous ignition of the high-pressure phase of RDX are presented using reactive molecular dynamics simulations. In order to initiate the chemistry behind thermal ignition, approximately 5% of RDX crystal is subjected to a constant temperature thermal pulse for various time durations to create a hot spot. After application of the thermal pulse, the ensuing chemical evolution of the system is monitored using reactive molecular dynamics under adiabatic conditions. Thermal pulses lasting longer than certain time durations lead to the spontaneous ignition of RDX after an incubation period. For cases where the ignition is observed, the incubation period is dominated by intermolecular and intramolecular hydrogen transfer reactions. Contrary to the widely accepted unimolecular models of initiation chemistry, N-N bond dissociations that produce NO2 species are suppressed in the condensed phase. The gradual temperature and pressure increase in the incubation period is accompanied by the accumulation of short-lived, heavier polyradicals. The polyradicals contain intact triazine rings from the RDX molecules. At certain temperatures and pressures, the polyradicals undergo ring-opening reactions, which fuel a series of rapid exothermic chemical reactions leading to a thermal runaway regime with stable gas-products such as N2, H2O and CO2. The evolution of the RDX crystal throughout the thermal initiation, incubation and thermal runaway phases observed in the reactive simulations contains a rich diversity of condensed-phase chemistry of nitramines under high-temperature/pressure conditions.

Microseismic Event Grouping Based on PageRank Linkage at the Newberry Volcano Geothermal Site

NASA Astrophysics Data System (ADS)

Aguiar, A. C.; Myers, S. C.

2016-12-01

The Newberry Volcano DOE FORGE site in Central Oregon has been stimulated two times using high-pressure fluid injection to study the Enhanced Geothermal Systems (EGS) technology. Several hundred microseismic events were generated during the first stimulation in the fall of 2012. Initial locations of this microseismicity do not show well defined subsurface structure in part because event location uncertainties are large (Foulger and Julian, 2013). We focus on this stimulation to explore the spatial and temporal development of microseismicity, which is key to understanding how subsurface stimulation modifies stress, fractures rock, and increases permeability. We use PageRank, Google's initial search algorithm, to determine connectivity within the events (Aguiar and Beroza, 2014) and assess signal-correlation topology for the micro-earthquakes. We then use this information to create signal families and compare these to the spatial and temporal proximity of associated earthquakes. We relocate events within families (identified by PageRank linkage) using the Bayesloc approach (Myers et al., 2007). Preliminary relocations show tight spatial clustering of event families as well as evidence of events relocating to a different cluster than originally reported. We also find that signal similarity (linkage) at several stations, not just one or two, is needed in order to determine that events are in close proximity to one another. We show that indirect linkage of signals using PageRank is a reliable way to increase the number of events that are confidently determined to be similar to one another, which may lead to efficient and effective grouping of earthquakes with similar physical characteristics, such as focal mechanisms and stress drop. Our ultimate goal is to determine whether changes in the state of stress and/or changes in the generation of subsurface fracture networks can be detected using PageRank topology as well as aid in the event relocation to obtain more accurate subsurface structure. Prepared by LLNL under Contract DE-AC52-07NA27344. LLNL-ABS-699142.

Regulation of ROS Production and Vascular Function by Carbon Monoxide

PubMed Central

Choi, Yoon Kyung; Por, Elaine D.; Kwon, Young-Guen; Kim, Young-Myeong

2012-01-01

Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). CO interacts with reduced iron of heme-containing proteins, leading to its involvement in various cellular events via its production of mitochondrial reactive oxygen species (ROS). CO-mediated ROS production initiates intracellular signal events, which regulate the expression of adaptive genes implicated in oxidative stress and functions as signaling molecule for promoting vascular functions, including angiogenesis and mitochondrial biogenesis. Therefore, CO generated either by exogenous delivery or by HO activity can be fundamentally involved in regulating mitochondria-mediated redox cascades for adaptive gene expression and improving blood circulation (i.e., O2 delivery) via neovascularization, leading to the regulation of mitochondrial energy metabolism. This paper will highlight the biological effects of CO on ROS generation and cellular redox changes involved in mitochondrial metabolism and angiogenesis. Moreover, cellular mechanisms by which CO is exploited for disease prevention and therapeutic applications will also be discussed. PMID:22928087

Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms

PubMed Central

Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano

2015-01-01

The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762

Pre-attentive processing of spectrally complex sounds with asynchronous onsets: an event-related potential study with human subjects.

PubMed

Tervaniemi, M; Schröger, E; Näätänen, R

1997-05-23

Neuronal mechanisms involved in the processing of complex sounds with asynchronous onsets were studied in reading subjects. The sound onset asynchrony (SOA) between the leading partial and the remaining complex tone was varied between 0 and 360 ms. Infrequently occurring deviant sounds (in which one out of 10 harmonics was different in pitch relative to the frequently occurring standard sound) elicited the mismatch negativity (MMN), a change-specific cortical event-related potential (ERP) component. This indicates that the pitch of standard stimuli had been pre-attentively coded by sensory-memory traces. Moreover, when the complex-tone onset fell within temporal integration window initiated by the leading-partial onset, the deviants elicited the N2b component. This indexes that involuntary attention switch towards the sound change occurred. In summary, the present results support the existence of pre-perceptual integration mechanism of 100-200 ms duration and emphasize its importance in switching attention towards the stimulus change.

Oscillation of neutrinos produced by the annihilation of dark matter inside the Sun

DOE Office of Scientific and Technical Information (OSTI.GOV)

Esmaili, Arman; School of Physics, Institute for Research in Fundamental Sciences; Farzan, Yasaman

2010-06-01

The annihilation of dark matter particles captured by the Sun can lead to a neutrino flux observable in neutrino detectors. Considering the fact that these dark matter particles are nonrelativistic, if a pair of dark matter annihilates to a neutrino pair, the spectrum of neutrinos will be monochromatic. We show that in this case, even after averaging over the production point inside the Sun, the oscillatory terms of the oscillation probability do not average to zero. This leads to interesting observable features in the annual variation of the number of muon track events. We show that smearing of the spectrummore » due to thermal distribution of dark matter inside the Sun is too small to wash out this variation. We point out the possibility of studying the initial flavor composition of neutrinos produced by the annihilation of dark matter particles via measuring the annual variation of the number of {mu}-track events in neutrino telescopes.« less

Mineral dust photochemistry induces nucleation events in the presence of SO2

PubMed Central

Dupart, Yoan; King, Stephanie M.; Nekat, Bettina; Nowak, Andreas; Wiedensohler, Alfred; Herrmann, Hartmut; David, Gregory; Thomas, Benjamin; Miffre, Alain; Rairoux, Patrick; D’Anna, Barbara; George, Christian

2012-01-01

Large quantities of mineral dust particles are frequently ejected into the atmosphere through the action of wind. The surface of dust particles acts as a sink for many gases, such as sulfur dioxide. It is well known that under most conditions, sulfur dioxide reacts on dust particle surfaces, leading to the production of sulfate ions. In this report, for specific atmospheric conditions, we provide evidence for an alternate pathway in which a series of reactions under solar UV light produces first gaseous sulfuric acid as an intermediate product before surface-bound sulfate. Metal oxides present in mineral dust act as atmospheric photocatalysts promoting the formation of gaseous OH radicals, which initiate the conversion of SO2 to H2SO4 in the vicinity of dust particles. Under low dust conditions, this process may lead to nucleation events in the atmosphere. The laboratory findings are supported by recent field observations near Beijing, China, and Lyon, France. PMID:23213230

W -Boson Production in Association with a Jet at Next-to-Next-to-Leading Order in Perturbative QCD

NASA Astrophysics Data System (ADS)

Boughezal, Radja; Focke, Christfried; Liu, Xiaohui; Petriello, Frank

2015-08-01

We present the complete calculation of W -boson production in association with a jet in hadronic collisions through next-to-next-to-leading order (NNLO) in perturbative QCD. To cancel infrared divergences, we discuss a new subtraction method that exploits the fact that the N -jettiness event-shape variable fully captures the singularity structure of QCD amplitudes with final-state partons. This method holds for processes with an arbitrary number of jets and is easily implemented into existing frameworks for higher-order calculations. We present initial phenomenological results for W +jet production at the LHC. The NNLO corrections are small and lead to a significantly reduced theoretical error, opening the door to precision measurements in the W +jet channel at the LHC.

Event plane dependence of the flow modulated background in dihadron and jet-hadron correlations in heavy ion collisions

NASA Astrophysics Data System (ADS)

Nattrass, Christine; Todoroki, Takahito

2018-05-01

Dihadron and jet-hadron correlationsare commonly used in relativistic heavy ion collisions to study the soft component of jets in a quark gluon plasma. There is a large correlated background which is described by the Fourier decomposition of the azimuthal anisotropy where vn is the n th order coefficient. The path length dependence of partonic energy loss can be studied by varying the angle of the high momentum trigger particle or jet relative to a reconstructed event plane. This modifies the shape of the background correlated with that event plane. The original derivation of the shape of this background only considered correlations relative to the second-order event plane, which is correlated to the initial participant plane. We derive the shape of this background for an event plane at an arbitrary order. There is a phase shift in the case of jets restricted to asymmetric regions relative to the event plane. For realistic correlations between event planes, the correlation between the second- and fourth-order event planes leads to a much smaller effect than the finite event plane resolution at each order. Finally, we assess the status of the rapidity even v1 term due to flow, which has been measured to be comparable to v2 and v3 terms.

Gunbarrel mafic magmatic event: A key 780 Ma time marker for Rodinia plate reconstructions

USGS Publications Warehouse

Harlan, S.S.; Heaman, L.; LeCheminant, A.N.; Premo, W.R.

2003-01-01

Precise U-Pb baddeleyite dating of mafic igneous rocks provides evidence for a widespread and synchronous magmatic event that extended for >2400 km along the western margin of the Neoproterozoic Laurentian craton. U-Pb baddeleyite analyses for eight intrusions from seven localities ranging from the northern Canadian Shield to northwestern Wyoming-southwestern Montana are statistically indistinguishable and yield a composite U-Pb concordia age for this event of 780.3 ?? 1.4 Ma (95% confidence level). This 780 Ma event is herein termed the Gunbarrel magmatic event. The mafic magmatism of the Gunbarrel event represents the largest mafic dike swarm yet identified along the Neoproterozoic margin of Laurentia. The origin of the mafic magmatism is not clear, but may be related to mantle-plume activity or upwelling asthenosphere leading to crustal extension accompanying initial breakup of the supercontinent Rodinia and development of the proto-Pacific Ocean. The mafic magmatism of the Gunbarrel magmatic event at 780 Ma predates the voluminous magmatism of the 723 Ma Franklin igneous event of the northwestern Canadian Shield by ???60 m.y. The precise dating of the extensive Neoproterozoic Gunbarrel and Franklin magmatic events provides unique time markers that can ultimately be used for robust testing of Neoproterozoic continental reconstructions.

Debris flow initiation by runoff in a recently burned basin: Is grain-by-grain sediment bulking or en masse failure to blame?

NASA Astrophysics Data System (ADS)

McGuire, Luke A.; Rengers, Francis K.; Kean, Jason W.; Staley, Dennis M.

2017-07-01

Postwildfire debris flows are frequently triggered by runoff following high-intensity rainfall, but the physical mechanisms by which water-dominated flows transition to debris flows are poorly understood relative to debris flow initiation from shallow landslides. In this study, we combined a numerical model with high-resolution hydrologic and geomorphic data sets to test two different hypotheses for debris flow initiation during a rainfall event that produced numerous debris flows within a recently burned drainage basin. Based on simulations, large volumes of sediment eroded from the hillslopes were redeposited within the channel network throughout the storm, leading to the initiation of numerous debris flows as a result of the mass failure of sediment dams that built up within the channel. More generally, results provide a quantitative framework for assessing the potential of runoff-generated debris flows based on sediment supply and hydrologic conditions.

Debris flow initiation by runoff in a recently burned basin: Is grain-by-grain sediment bulking or en masse failure to blame?

USGS Publications Warehouse

McGuire, Luke; Rengers, Francis K.; Kean, Jason W.; Staley, Dennis M.

2017-01-01

Postwildfire debris flows are frequently triggered by runoff following high-intensity rainfall, but the physical mechanisms by which water-dominated flows transition to debris flows are poorly understood relative to debris flow initiation from shallow landslides. In this study, we combined a numerical model with high-resolution hydrologic and geomorphic data sets to test two different hypotheses for debris flow initiation during a rainfall event that produced numerous debris flows within a recently burned drainage basin. Based on simulations, large volumes of sediment eroded from the hillslopes were redeposited within the channel network throughout the storm, leading to the initiation of numerous debris flows as a result of the mass failure of sediment dams that built up within the channel. More generally, results provide a quantitative framework for assessing the potential of runoff-generated debris flows based on sediment supply and hydrologic conditions.

Assessing various approaches for flash flood forecasting in the Yzeron periurban catchment (150 km2) south-east Lyon, France

NASA Astrophysics Data System (ADS)

Braud, Isabelle; Breil, Pascal; Javelle, Pierre; Pejakovic, Nikola; Guérin, Stéphane

2017-04-01

The Yzeron periurban catchment (150 km2) is prone to flash floods leading to overflow in the downstream part of the catchment. A prevention and management plan has been approved and the set-up of a flood forecasting system is planned. The present study presents a comparison of several solutions for flood forecasting in the catchment. It is based on an extensive data collection (rain gauges, radar/rain gauge reanalyses, discharge and water level data) from this experimental catchment. A set of rainfall-runoff events leading to floods (problematic and non-problematic floods) was extracted and formed the basis for the definition of a first forecasting method. It is based on data analysis and the identification of explaining factors amongst the following: rainfall amount, intensity, antecedent rainfall, initial discharge. Several statistical methods including Factorial Analysis of Mixed Data and Classification and Regression Tree were used for this purpose. They showed that several classes of problematic floods can be identified. The first one is related to wet conditions characterized with high initial discharge and antecedent rainfall. The second class is driven by rainfall amount, initial discharge and rainfall intensity. Thresholds of these variables can be identified to provide a first warning. The second forecasting method assessed in the study is the system that will be operational in France in 2017, based on the AIGA method (Javelle et al., 2016). For this purpose, 18-year discharge simulation using the hydrological model of the AIGA method, forced using radar/rain gauges reanalysis were available at 44 locations within the catchment. The dates for which quantiles of a given return period were overtopped were identified and compared with the list of problematic events. The AIGA method was found relevant in identifying the most problematic events, but the lead time needs further investigation in order to assess the usefulness for population warning. References: Pierre Javelle, Didier Organde, Julie Demargne, Clotilde Saint-Martin, Céline de Saint-Aubin, Léa Garandeau and Bruno Janet (2016). Setting up a French national flash flood warning system for ungauged catchments based on the AIGA method. E3S Web of Conferences 7, 18010 (2016), 3rd European Conference on Flood Risk Management (FLOODrisk 2016), http://dx.doi.org/10.1051/e3sconf/20160718010

Prospective Association Between Negative Life Events and Initiation of Sexual Intercourse: The Influence of Family Structure and Family Income

PubMed Central

Oman, Roy F.; Vesely, Sara K.; Aspy, Cheryl B.; Tolma, Eleni L.; John, Robert

2015-01-01

Objectives. We examined the prospective association between negative life events and time to initiation of sexual intercourse and the influence of family structure and family income on this association. Methods. We followed up a randomly selected sample (n = 649) of ethnically diverse parents and their children aged 12 to 17 years over a 5-year period. We conducted Cox proportional hazards regression analysis to examine the relation between negative life events and time to initiation of sexual intercourse. Family structure and family income were assessed as confounders. Results. Negative life events were significant predictors of time to initiation of sexual intercourse in adolescents. After controlling for demographic variables, youths reporting 1 negative life event had a hazard of initiation of sexual intercourse 1.40 times greater and youths reporting 2 or more negative life events had a hazard of initiation of sexual intercourse 1.61 times greater compared with youths reporting no negative life events. Family structure and family income were not significant confounders of the relation between initiation of sexual intercourse and negative life events. Conclusions. Interventions to prevent initiation of sexual intercourse should focus on youths with recent negative life events, regardless of family income and structure. PMID:25602885

Reliability of windstorm predictions in the ECMWF ensemble prediction system

NASA Astrophysics Data System (ADS)

Becker, Nico; Ulbrich, Uwe

2016-04-01

Windstorms caused by extratropical cyclones are one of the most dangerous natural hazards in the European region. Therefore, reliable predictions of such storm events are needed. Case studies have shown that ensemble prediction systems (EPS) are able to provide useful information about windstorms between two and five days prior to the event. In this work, ensemble predictions with the European Centre for Medium-Range Weather Forecasts (ECMWF) EPS are evaluated in a four year period. Within the 50 ensemble members, which are initialized every 12 hours and are run for 10 days, windstorms are identified and tracked in time and space. By using a clustering approach, different predictions of the same storm are identified in the different ensemble members and compared to reanalysis data. The occurrence probability of the predicted storms is estimated by fitting a bivariate normal distribution to the storm track positions. Our results show, for example, that predicted storm clusters with occurrence probabilities of more than 50% have a matching observed storm in 80% of all cases at a lead time of two days. The predicted occurrence probabilities are reliable up to 3 days lead time. At longer lead times the occurrence probabilities are overestimated by the EPS.

Inflammation, leukocytes and menstruation.

PubMed

Evans, Jemma; Salamonsen, Lois A

2012-12-01

Menstruation has many of the features of an inflammatory process. The complexity and sequence of inflammatory-type events leading to the final tissue breakdown and bleeding are slowly being unravelled. Progesterone has anti-inflammatory properties, and its rapidly declining levels (along with those of estrogen) in the late secretory phase of each non-conception cycle, initiates a sequence of interdependent events of an inflammatory nature involving local inter-cellular interactions within the endometrium. Intracellular responses to loss of progesterone (in decidualized stromal, vascular and epithelial cells) lead to decreased prostaglandin metabolism and loss of protection from reactive oxygen species (ROS). Increased ROS results in release of NFκB from suppression with activation of target gene transcription and increased synthesis of pro-inflammatory prostaglandins, cytokines, chemokines and matrix metalloproteinases (MMP). The resultant leukocyte recruitment, with changing phenotypes and activation, provide further degradative enzymes and MMP activators, which together with a hypoxic environment induced by prostaglandin actions, lead to the tissue breakdown and bleeding characteristic of menstruation. In parallel, at sites where shedding is complete, microenvironmentally-induced changes in phenotypes of neutrophils and macrophages from pro- to anti-inflammatory, in addition to induction of growth factors, contribute to the very rapid re-epithelialization and restoration of tissue integrity.

Analytical simulation and PROFAT II: a new methodology and a computer automated tool for fault tree analysis in chemical process industries.

PubMed

Khan, F I; Abbasi, S A

2000-07-10

Fault tree analysis (FTA) is based on constructing a hypothetical tree of base events (initiating events) branching into numerous other sub-events, propagating the fault and eventually leading to the top event (accident). It has been a powerful technique used traditionally in identifying hazards in nuclear installations and power industries. As the systematic articulation of the fault tree is associated with assigning probabilities to each fault, the exercise is also sometimes called probabilistic risk assessment. But powerful as this technique is, it is also very cumbersome and costly, limiting its area of application. We have developed a new algorithm based on analytical simulation (named as AS-II), which makes the application of FTA simpler, quicker, and cheaper; thus opening up the possibility of its wider use in risk assessment in chemical process industries. Based on the methodology we have developed a computer-automated tool. The details are presented in this paper.

Predictability of the atmospheric conditions leading to extreme weather events in the Western Mediterranean Region in comparison with the seasonal mean conditions

NASA Astrophysics Data System (ADS)

Khodayar, Samiro; Kalthoff, Norbert

2013-04-01

Among all severe convective weather situations, fall season heavy rainfall represents the most threatening phenomenon in the western Mediterranean region. Devastating flash floods occur every year somewhere in eastern Spain, southern France, Italy, or North Africa, being responsible for a great proportion of the fatalities, property losses, and destruction of infrastructure caused by natural hazards. Investigations in the area have shown that most of the heavy rainfall events in this region can be attributed to mesoscale convective systems. The main goal of this investigation is to understand and identify the atmospheric conditions that favor the initiation and development of such systems. Insight of the involved processes and conditions will improve their predictability and help preventing some of the fatal consequences related with the occurrence of these weather phenomena. The HyMeX (Hydrological cycle in the Mediterranean eXperiment) provides a unique framework to investigate this issue. Making use of high-resolution seasonal simulations with the COSMO-CLM model the mean atmospheric conditions of the fall season, September, October and November, are investigated in different western Mediterranean regions such as eastern Spain, Southern France, northern Africa and Italy. The precipitation distribution, its daily cycle, and probability distribution function are evaluated to ascertain the similarities and differences between the regions of interest, as well as the spatial distribution of extreme events. Additionally, the regional differences of the boundary layer and mid-tropospheric conditions, atmospheric stability and inhibition, and low-level triggering are presented. Selected high impact weather HyMeX episodes' are analyzed with special focus on the atmospheric pre-conditions leading to the extreme weather situations. These pre-conditions are then compared to the mean seasonal conditions to identify and point out possible anomalies in the atmospheric conditions which could favor the initiation and intensification of extreme precipitation weather events.

Breastfeeding Initiation and Maintenance Among African Americans and Blacks Enrolled in a Nurse Home Visitation Program: An Outcomes Focused Program Evaluation

DTIC Science & Technology

2013-12-11

coupled relationship (i.e., married or unmarried couple) breastfeeding were nearly 3.8 times as likely as women who were not in a coupled relationship...support, negative life events, being unmarried , and certain maternal hospital experiences, which may lead to formula supplementation. Moreover, these...live births, without chronic illnesses that might adversely affect the fetus, and with at least two socioeconomic risk factors (e.g., unmarried

Orthodontist's Role in Orthognathic Surgery

PubMed Central

Wirthlin, John O.; Shetye, Pradip R.

2013-01-01

Orthognathic surgery can eliminate severe esthetic and functional deformities and be a life-changing event for a patient. An orthodontist's role in orthognathic surgery can be divided into several phases: the initial evaluation, presurgical orthodontics, surgical planning, and postsurgical orthodontics. At each of these phases, collaboration between the orthodontist and the surgeon is critical. The ability of an orthodontist and a surgeon to coordinate their efforts during this time is what will lead to a successful outcome. PMID:24872759

Measurement of jet charge in dijet events from $$\\sqrt{s}$$ = 8 TeV $pp$ collisions with the ATLAS detector

DOE PAGES

Aad, G.; Abbott, B.; Abdallah, J.; ...

2016-03-02

In this study, the momentum-weighted sum of the charges of tracks associated to a jet is sensitive to the charge of the initiating quark or gluon. This paper presents a measurement of the distribution of momentum-weighted sums, called jet charge, in dijet events using 20.3 fb -1 of data recorded with the ATLAS detector at √s = 8 TeV in pp collisions at the LHC. The jet charge distribution is unfolded to remove distortions from detector effects and the resulting particle-level distribution is compared with several models. The p T dependence of the jet charge distribution average and standard deviationmore » are compared to predictions obtained with several leading-order and next-to-leading-order parton distribution functions. The data are also compared to different Monte Carlo simulations of QCD dijet production using various settings of the free parameters within these models. The chosen value of the strong coupling constant used to calculate gluon radiation is found to have a significant impact on the predicted jet charge. There is evidence for a p T dependence of the jet charge distribution for a given jet flavor. In agreement with perturbative QCD predictions, the data show that the average jet charge of quark-initiated jets decreases in magnitude as the energy of the jet increases.« less

KENNEDY SPACE CENTER, FLA. - KSC Director Jim Kennedy and Glenn Research Center Director Dr. Julian Earls share the stage during the rollout of the One NASA initiative at KSC. Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Kennedy and Earls, were James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson.

NASA Image and Video Library

2003-08-20

KENNEDY SPACE CENTER, FLA. - KSC Director Jim Kennedy and Glenn Research Center Director Dr. Julian Earls share the stage during the rollout of the One NASA initiative at KSC. Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Kennedy and Earls, were James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson.

KENNEDY SPACE CENTER, FLA. - Dryden Flight Research Center Director Kevin Peterson talks about One NASA during the rollout of the Agency initiative at KSC. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Peterson, were KSC Director Jim Kennedy, James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

NASA Image and Video Library

2003-08-20

KENNEDY SPACE CENTER, FLA. - Dryden Flight Research Center Director Kevin Peterson talks about One NASA during the rollout of the Agency initiative at KSC. The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Peterson, were KSC Director Jim Kennedy, James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; incoming KSC Deputy Director Woodrow Whitlow; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

KENNEDY SPACE CENTER, FLA. - KSC’s incoming Deputy Director Woodrow Whitlow speaks to employees and guests during the rollout at KSC of the Agency initiative One NASA . The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Whitlow, were KSC Director Jim Kennedy; James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

NASA Image and Video Library

2003-08-20

KENNEDY SPACE CENTER, FLA. - KSC’s incoming Deputy Director Woodrow Whitlow speaks to employees and guests during the rollout at KSC of the Agency initiative One NASA . The event was held at the IMAX Theater® where NASA leaders discussed One NASA with selected employees. Explaining how their respective centers contribute to One NASA, along with Whitlow, were KSC Director Jim Kennedy; James Jennings, NASA’s associate deputy administrator for institutions and asset management; Ed Weiler, associate administrator for Space Science; Kevin Peterson, Dryden Flight Research Center director; and implementation team lead Johnny Stevenson. Glenn Research Center Director Dr. Julian Earls gave a motivational speech during the luncheon held at the Visitor Complex Debus Conference Center.

Combined Aspirin and Anticoagulant Therapy in Patients with Atrial Fibrillation

PubMed Central

So, Charlotte H.; Eckman, Mark H.

2016-01-01

Background The combined use of aspirin and oral anticoagulant therapy in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) has been questioned due to an increased risk of major bleeding with little to no benefit in preventing ischemic events. Objective (1) To better understand patterns and indications for combined antiplatelet and anticoagulant therapy and identify patients who might reasonably be treated with oral anticoagulant (OAC) therapy alone. (2) To perform an updated literature review regarding the use of combined antiplatelet and OAC therapy in patients with AF and stable CAD. Design and Participants Retrospective review. Patients within the University of Cincinnati Health System with a diagnosis of non-valvular AF, excluding those with acute coronary syndrome or revascularization within the last 12 months. Main Measures Numbers and indications for combined antiplatelet and anticoagulant therapy and sequence of events leading to the initiation of each. Key Results Of 948 patients receiving OAC, 430 (45%) were receiving concomitant OAC and aspirin. Among patients receiving combined antiplatelet and anticoagulant therapy, 49% and 42% of patients respectively, had CAD or DM. In a more detailed analysis including chart review of 219 patients receiving combined OAC and aspirin, 27% had a diagnosis of CAD and 14% had a diagnosis of DM prior to the development of AF. These patients were initially treated with aspirin. Warfarin was added when they subsequently developed AF but aspirin wasn’t discontinued. A surprisingly large proportion of patients (22.8%) had no obvious indication for dual therapy. Conclusions Prior myocardial infarction, CAD, vascular disease and DM (among others) increase the likelihood of receiving combined antiplatelet and anticoagulant therapy among patients with AF. A literature review suggests this may lead to increased major bleeding with little benefit in decreasing either AF-related stroke or cardiovascular events. PMID:27665101

Curcumin induces crosstalk between autophagy and apoptosis mediated by calcium release from the endoplasmic reticulum, lysosomal destabilization and mitochondrial events

PubMed Central

Moustapha, A; Pérétout, PA; Rainey, NE; Sureau, F; Geze, M; Petit, J-M; Dewailly, E; Slomianny, C; Petit, PX

2015-01-01

Curcumin, a major active component of turmeric (Curcuma longa, L.), has anticancer effects. In vitro studies suggest that curcumin inhibits cancer cell growth by activating apoptosis, but the mechanism underlying these effects is still unclear. Here, we investigated the mechanisms leading to apoptosis in curcumin-treated cells. Curcumin induced endoplasmic reticulum stress causing calcium release, with a destabilization of the mitochondrial compartment resulting in apoptosis. These events were also associated with lysosomal membrane permeabilization and of caspase-8 activation, mediated by cathepsins and calpains, leading to Bid cleavage. Truncated tBid disrupts mitochondrial homeostasis and enhance apoptosis. We followed the induction of autophagy, marked by the formation of autophagosomes, by staining with acridine orange in cells exposed curcumin. At this concentration, only the early events of apoptosis (initial mitochondrial destabilization with any other manifestations) were detectable. Western blotting demonstrated the conversion of LC3-I to LC3-II (light chain 3), a marker of active autophagosome formation. We also found that the production of reactive oxygen species and formation of autophagosomes following curcumin treatment was almost completely blocked by N-acetylcystein, the mitochondrial specific antioxidants MitoQ10 and SKQ1, the calcium chelators, EGTA-AM or BAPTA-AM, and the mitochondrial calcium uniporter inhibitor, ruthenium red. Curcumin-induced autophagy failed to rescue all cells and most cells underwent type II cell death following the initial autophagic processes. All together, these data imply a fail-secure mechanism regulated by autophagy in the action of curcumin, suggesting a therapeutic potential for curcumin. Offering a novel and effective strategy for the treatment of malignant cells. PMID:27551451

USCT data challenge

NASA Astrophysics Data System (ADS)

Ruiter, Nicole V.; Zapf, Michael; Hopp, Torsten; Gemmeke, Hartmut; van Dongen, Koen W. A.

2017-03-01

In the past years we have perceived within the USCT research community a demand for freely available USCT data sets. Inspired by the idea of Open Science, this collection of data sets could stimulate the collaboration and the exchange of ideas and experiences between USCT researchers. In addition, it may lead to comprehensive comparison of different reconstruction algorithms and their results. Finally, by collecting feedback from the users about data and system architecture, valuable information is gathered for further development of measurement setups. For the above reasons, we have initiated a digital portal with several reference data sets and access scripts under free licenses. To kick off this initiative, we organized a USCT data challenge event at SPIE Medical Imaging 2017.

Inherent Safety Characteristics of Advanced Fast Reactors

NASA Astrophysics Data System (ADS)

Bochkarev, A. S.; Korsun, A. S.; Kharitonov, V. S.; Alekseev, P. N.

2017-01-01

The study presents SFR transient performance for ULOF events initiated by pump trip and pump seizure with simultaneous failure of all shutdown systems in both cases. The most severe cases leading to the pin cladding rupture and possible sodium boiling are demonstrated. The impact of various features on SFR inherent safety performance for ULOF events was analysed. The decrease in hydraulic resistance of primary loop and increase in primary pump coast down time were investigated. Performing analysis resulted in a set of recommendations to varying parameters for the purpose of enhancing the inherent safety performance of SFR. In order to prevent the safety barrier rupture for ULOF events the set of thermal hydraulic criteria defining the ULOF transient processes dynamics and requirements to these criteria were recommended based on achieved results: primary sodium flow dip under the natural circulation asymptotic level and natural circulation rise time.

Non-Gaussian statistics of extreme events in stimulated Raman scattering: The role of coherent memory and source noise

NASA Astrophysics Data System (ADS)

Monfared, Yashar E.; Ponomarenko, Sergey A.

2017-10-01

We explore theoretically and numerically extreme event excitation in stimulated Raman scattering in gases. We consider gas-filled hollow-core photonic crystal fibers as a particular system realization. We show that moderate amplitude pump fluctuations obeying Gaussian statistics lead to the emergence of heavy-tailed non-Gaussian statistics as coherent seed Stokes pulses are amplified on propagation along the fiber. We reveal the crucial role that coherent memory effects play in causing non-Gaussian statistics of the system. We discover that extreme events can occur even at the initial stage of stimulated Raman scattering when one can neglect energy depletion of an intense, strongly fluctuating Gaussian pump source. Our analytical results in the undepleted pump approximation explicitly illustrate power-law probability density generation as the input pump noise is transferred to the output Stokes pulses.

The Impact of Ocean Data Assimilation on Seasonal-to-Interannual Forecasts: A Case Study of the 2006 El Nino Event

NASA Technical Reports Server (NTRS)

Yang, Shu-Chih; Rienecker, Michele; Keppenne, Christian

2010-01-01

This study investigates the impact of four different ocean analyses on coupled forecasts of the 2006 El Nino event. Forecasts initialized in June 2006 using ocean analyses from an assimilation that uses flow-dependent background error covariances are compared with those using static error covariances that are not flow dependent. The flow-dependent error covariances reflect the error structures related to the background ENSO instability and are generated by the coupled breeding method. The ocean analyses used in this study result from the assimilation of temperature and salinity, with the salinity data available from Argo floats. Of the analyses, the one using information from the coupled bred vectors (BV) replicates the observed equatorial long wave propagation best and exhibits more warming features leading to the 2006 El Nino event. The forecasts initialized from the BV-based analysis agree best with the observations in terms of the growth of the warm anomaly through two warming phases. This better performance is related to the impact of the salinity analysis on the state evolution in the equatorial thermocline. The early warming is traced back to salinity differences in the upper ocean of the equatorial central Pacific, while the second warming, corresponding to the mature phase, is associated with the effect of the salinity assimilation on the depth of the thermocline in the western equatorial Pacific. The series of forecast experiments conducted here show that the structure of the salinity in the initial conditions is important to the forecasts of the extension of the warm pool and the evolution of the 2006 El Ni o event.

S-allyl cysteine in combination with clotrimazole downregulates Fas induced apoptotic events in erythrocytes of mice exposed to lead.

PubMed

Mandal, Samir; Mukherjee, Sudip; Chowdhury, Kaustav Dutta; Sarkar, Avik; Basu, Kankana; Paul, Soumosish; Karmakar, Debasish; Chatterjee, Mahasweta; Biswas, Tuli; Sadhukhan, Gobinda Chandra; Sen, Gargi

2012-01-01

Chronic lead (Pb(2+)) exposure leads to the reduced lifespan of erythrocytes. Oxidative stress and K(+) loss accelerate Fas translocation into lipid raft microdomains inducing Fas mediated death signaling in these erythrocytes. Pathophysiological-based therapeutic strategies to combat against erythrocyte death were evaluated using garlic-derived organosulfur compounds like diallyl disulfide (DADS), S allyl cysteine (SAC) and imidazole based Gardos channel inhibitor clotrimazole (CLT). Morphological alterations in erythrocytes were evaluated using scanning electron microscopy. Events associated with erythrocyte death were evaluated using radio labeled probes, flow cytometry and activity gel assay. Mass spectrometry was used for detection of GSH-4-hydroxy-trans-2-nonenal (HNE) adducts. Fas redistribution into the lipid rafts was studied using immunoblotting technique and confocal microscopy. Combination of SAC and CLT was better than DADS and CLT combination and monotherapy with these agents in prolonging the survival of erythrocytes during chronic Pb(2+) exposure. Combination therapy with SAC and CLT prevented redistribution of Fas into the lipid rafts of the plasma membrane and downregulated Fas-dependent death events in erythrocytes of mice exposed to Pb(2+). Ceramide generation was a critical component of Fas receptor-induced apoptosis, since inhibition of acid sphingomyelinase (aSMase) interfered with Fas-induced apoptosis during Pb(2+) exposure. Combination therapy with SAC and CLT downregulated apoptotic events in erythrocytes by antagonizing oxidative stress and Gardos channel that led to suppression of ceramide-initiated Fas aggregation in lipid rafts. Hence, combination therapy with SAC and CLT may be a potential therapeutic option for enhancing the lifespan of erythrocytes during Pb(2+) toxicity. Copyright © 2011 Elsevier B.V. All rights reserved.

Evasion of cell senescence in SHH medulloblastoma.

PubMed

Tamayo-Orrego, Lukas; Swikert, Shannon M; Charron, Frédéric

2016-08-17

The mechanisms leading to brain tumor formation are poorly understood. Using Ptch1 +/- mice as a medulloblastoma model, sequential mutations were found to shape tumor evolution. Initially, medulloblastoma preneoplastic lesions display loss of heterozygosity of the Ptch1 wild-type allele, an event associated with cell senescence in preneoplasia. Subsequently, p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma. These findings are consistent with a model where high levels of Hedgehog signaling caused by the loss of the tumor suppressor Ptch1 lead to oncogene-induced senescence and drive p53 mutations. Thus, cell senescence is an important characteristic of a subset of SHH medulloblastoma and might explain the acquisition of somatic TP53 mutations in human medulloblastoma. This mode of medulloblastoma formation contrasts with the one characterizing Li-Fraumeni patients with medulloblastoma, where TP53 germ-line mutations cause chromothriptic genomic instability and lead to mutations in Hedgehog signaling genes, which drive medulloblastoma growth. Here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis.

Evasion of cell senescence in SHH medulloblastoma

PubMed Central

Tamayo-Orrego, Lukas; Swikert, Shannon M.; Charron, Frédéric

2016-01-01

ABSTRACT The mechanisms leading to brain tumor formation are poorly understood. Using Ptch1+/− mice as a medulloblastoma model, sequential mutations were found to shape tumor evolution. Initially, medulloblastoma preneoplastic lesions display loss of heterozygosity of the Ptch1 wild-type allele, an event associated with cell senescence in preneoplasia. Subsequently, p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma. These findings are consistent with a model where high levels of Hedgehog signaling caused by the loss of the tumor suppressor Ptch1 lead to oncogene-induced senescence and drive p53 mutations. Thus, cell senescence is an important characteristic of a subset of SHH medulloblastoma and might explain the acquisition of somatic TP53 mutations in human medulloblastoma. This mode of medulloblastoma formation contrasts with the one characterizing Li-Fraumeni patients with medulloblastoma, where TP53 germ-line mutations cause chromothriptic genomic instability and lead to mutations in Hedgehog signaling genes, which drive medulloblastoma growth. Here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis. PMID:27229128

Data driven analysis of rain events: feature extraction, clustering, microphysical /macro physical relationship

NASA Astrophysics Data System (ADS)

Djallel Dilmi, Mohamed; Mallet, Cécile; Barthes, Laurent; Chazottes, Aymeric

2017-04-01

The study of rain time series records is mainly carried out using rainfall rate or rain accumulation parameters estimated on a fixed integration time (typically 1 min, 1 hour or 1 day). In this study we used the concept of rain event. In fact, the discrete and intermittent natures of rain processes make the definition of some features inadequate when defined on a fixed duration. Long integration times (hour, day) lead to mix rainy and clear air periods in the same sample. Small integration time (seconds, minutes) will lead to noisy data with a great sensibility to detector characteristics. The analysis on the whole rain event instead of individual short duration samples of a fixed duration allows to clarify relationships between features, in particular between macro physical and microphysical ones. This approach allows suppressing the intra-event variability partly due to measurement uncertainties and allows focusing on physical processes. An algorithm based on Genetic Algorithm (GA) and Self Organising Maps (SOM) is developed to obtain a parsimonious characterisation of rain events using a minimal set of variables. The use of self-organizing map (SOM) is justified by the fact that it allows to map a high dimensional data space in a two-dimensional space while preserving as much as possible the initial space topology in an unsupervised way. The obtained SOM allows providing the dependencies between variables and consequently removing redundant variables leading to a minimal subset of only five features (the event duration, the rain rate peak, the rain event depth, the event rain rate standard deviation and the absolute rain rate variation of order 0.5). To confirm relevance of the five selected features the corresponding SOM is analyzed. This analysis shows clearly the existence of relationships between features. It also shows the independence of the inter-event time (IETp) feature or the weak dependence of the Dry percentage in event (Dd%e) feature. This confirms that a rain time series can be considered by an alternation of independent rain event and no rain period. The five selected feature are used to perform a hierarchical clustering of the events. The well-known division between stratiform and convective events appears clearly. This classification into two classes is then refined in 5 fairly homogeneous subclasses. The data driven analysis performed on whole rain events instead of fixed length samples allows identifying strong relationships between macrophysics (based on rain rate) and microphysics (based on raindrops) features. We show that among the 5 identified subclasses some of them have specific microphysics characteristics. Obtaining information on microphysical characteristics of rainfall events from rain gauges measurement suggests many implications in development of the quantitative precipitation estimation (QPE), for the improvement of rain rate retrieval algorithm in remote sensing context.

Evaluation of thromboembolic events in cancer patients receiving bevacizumab according to the Japanese Adverse Drug Event Report database.

PubMed

Matsumura, Chikako; Chisaki, Yugo; Sakimoto, Satoko; Sakae, Honoka; Yano, Yoshitaka

2018-01-01

Purpose We aimed to examine the risk factors, time of onset, incidence rates, and outcomes of thromboembolic events induced by bevacizumab in patients with cancer using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceuticals and Medical Devices Agency. Methods Adverse event data recorded in the JADER database between January 2004 and January 2015 were used. After screening the data using the generic drug name bevacizumab, patient data were classified into two groups by age and five groups by cancer type. The histories of disorders were also categorized. Arterial thromboembolic event and venous thromboembolic event were classified as "favorable" or "unfavorable" outcomes. Results In total, 6076 patients were reported to have developed adverse events during the sample period, of which 233 and 453 developed arterial thromboembolic event and venous thromboembolic event, respectively. Logistic analysis suggested that the presence of cancer was a significant risk factor for both arterial thromboembolic event and venous thromboembolic event. Age (≥70 years), histories of either hypertension or diabetes mellitus were also risk factors for arterial thromboembolic event. Median cumulative times of onset for arterial thromboembolic event and venous thromboembolic event were 60 and 80 days, respectively, and were not significantly different by the log-rank test. By the chi-square test, the rate of unfavorable outcomes was found to be higher after developing arterial thromboembolic event than after venous thromboembolic event. Conclusion Thromboembolism is a leading cause of mortality in patients with cancer. Patients should be monitored for the symptoms of thromboembolic events right from the initial stages of bevacizumab treatment.

On the Principles of Building a Layered Intrusion

NASA Astrophysics Data System (ADS)

Marsh, B. D.

2009-12-01

An accurate and realistic understanding of all magmatic processes involves knowing the combined physical and chemical fundamentals governing the overall process. Magmatic processes involve such a vast array of sub-processes (e.g., heat and mass transfer, crystal growth, slurry transport and sorting, annealing, resorbtion, etc.) that rarely is there any single feature or measurement that can be safely inverted to solve the problem. And each event as in the formation of an intrusion must at some level for heuristic purposes be defined as an isolated event. This is commonly done without much forethought, as is the absolutely critical assumption of the initial conditions defining the beginning of the event. Almost without exception, it is the initial conditions that determine the outcome of the entire process in all physical and biological systems. Automobile factories produce motorized vehicles not water melons or chimpanzees. Nucleosynthesis of H and He always gives the same set of elements. The initial conditions of the magma giving rise to the end product for mafic layered systems are especially difficult to discern and must be bounded by observing simpler, real time magmatic and volcanic processes. Initial conditions come from posing a series of questions: What was the style and duration of filling? What was the rate of influx and final volume of each delivery of magma? What was the compositional variation and phenocryst content of the individual magmatic deliveries? If phenocrysts are present, were they sorted prior to injection during ascension? What was the original and ongoing shape of the magmatic reservoir? A failure to appreciate or answer such basic questions leads to vastly untenable evolutionary scenarios. Unrealistic initial conditions necessarily lead to unrealistic magmatic scenarios. There are certain safe starting points. Eruptive and emplacement fluxes are limited. The larger an intrusion is the longer it took to build and the longer to build the more varied are the deliveries in time, volume, and constitution. Instantaneous emplacement of crystal free magma are unlikely initial conditions for a large intrusion. The most realistic initial conditions are that intrusions are made of a combination of crystal poor and crystal-rich inputs. Examples abound of the outcomes of systems with clearly known initial conditions. The huge Sudbury magma was produced in 5 minutes at a temperature of 1700C. Clearly crystal free, it produced no layering whatsoever. Sills worldwide, regardless of size, approaching these initial conditions are similarly featureless. At the other extreme are the lava outputs of large volcanic systems like Kilauea. The ensuing lava lakes produced over months are filled with magma containing varied amounts of phenocrysts/xenocrysts and ultramafic layers are produced. Intrusions abound of all sizes that show the same characteristics. Ponding in crystal-laden sills forms layered systems with many of the features of large bodies. Rapid cooling preserves diagnostic textural relations lost to annealing in large bodies. Slow cooling promotes annealing to sharpen and accentuate the initial modal and cryptic layering. Initial conditions are fundamental to understanding the final product. Physical processes buttressed by chemistry mainly dominate magmatic systems.

The Role of Hemoglobin Laboratory Test Results for the Detection of Upper Gastrointestinal Bleeding Outcomes Resulting from the Use of Medications in Observational Studies.

PubMed

Patorno, Elisabetta; Gagne, Joshua J; Lu, Christine Y; Haynes, Kevin; Sterrett, Andrew T; Roy, Jason; Wang, Xingmei; Raebel, Marsha A

2017-01-01

The identification of upper gastrointestinal (UGI) bleeding and perforated ulcers in claims data typically relies on inpatient diagnoses. The use of hemoglobin laboratory results might increase the detection of UGI events that do not lead to hospitalization. Our objective was to evaluate whether hemoglobin results increase UGI outcome identification in electronic databases, using non-steroidal anti-inflammatory drugs (NSAIDs) as a test case. From three data partner sites within the Mini-Sentinel Distributed Database, we identified NSAID initiators aged ≥18 years between 2008 and 2013. Numbers of events and risks within 30 days after NSAID initiation were calculated for four mutually exclusive outcomes: (1) inpatient UGI diagnosis of bleeding or gastric ulcer (standard claims-based definition without laboratory results); (2) non-inpatient UGI diagnosis AND ≥3 g/dl hemoglobin decrease; (3) ≥3 g/dl hemoglobin decrease without UGI diagnosis in any clinical setting; (4) non-inpatient UGI diagnosis, without ≥3 g/dl hemoglobin decrease. We identified 2,289,772 NSAID initiators across three sites. Overall, 45.3% had one or more hemoglobin result available within 365 days before or 30 days after NSAID initiation; only 6.8% had results before and after. Of 7637 potential outcomes identified, outcome 1 accounted for 21.7%, outcome 2 for 0.8%, outcome 3 for 34.3%, and outcome 4 for 43.3%. Potential cases identified by outcome 3 were largely not suggestive of UGI events. Outcomes 1, 2, and 4 had similar distributions of specific UGI diagnoses. Using available hemoglobin result values combined with non-inpatient UGI diagnoses identified few additional UGI cases. Non-inpatient UGI diagnostic codes may increase outcome detection but would require validation.

The National Data Center Preparedness Exercise 2009 - First Results

NASA Astrophysics Data System (ADS)

Gestermann, Nicolai; Bönnemann, Christian; Ceranna, Lars; Wotawa, Gerhard

2010-05-01

The NDC preparedness initiative was initiated by 8 signature states. It has now a history of more than 2 years with two successful exercises and subsequent fruitful discussions during the NDC Evaluation Workshops of the CTBTO. The first exercise was carried out in 2007 (NPE07). The objectives of and the idea behind this exercise have been described in the working paper CTBT/WGB-28/DE-IT/1 of the CTBTO. The exercise simulates a fictitious violation of the CTBT and all NDCs are invited to clarify the nature of the selected event. This exercise should help to evaluate the effectiveness of analysis procedures applied at NDCs, as well as the quality, completeness, and usefulness of IDC products. Moreover, the NPE is a measure for the readiness of the NDCs to fulfil their duties in regard of the CTBT verification: the treaty compliance based judgments about the nature of events as natural or artificial and chemical or nuclear, respectively. The NPE09 has started on 1 October 2009, 00:00 UTC. In addition to the previous exercises, three technologies (seismology, infrasound, and radionuclide) have been taken into account leading to tentative mock events generated by strong explosions in open pit mines. Consequently, the first event, which fulfils all previously defined criteria, was close to the Kara-Zhyra mine in Eastern Kazakhstan and occurred on 28 November 2009 at 07:20:31 UTC. It generated seismic signals as well as infrasound signals at the closest IMS stations. The forward atmospheric transport modelling indicated that a sufficient number of radionuclide stations were also affected to enable the application of a negative testing scenario. First results of the seismo-acoustic analysis of the NPE09 event were presented along with details on the event selection process.

Prediction of Significant Wave Heights in the Tropics at Sub-seasonal Time Scales

NASA Astrophysics Data System (ADS)

Kinter, J. L.; Shukla, R. P.; Shin, C. S.

2017-12-01

Skillfully predicting the 14-day mean significant wave height (SWH) forecasts at 3 weeks lead-time over the Western Pacific and Indian Oceans has been demonstrated using the WAVEWATCH-3 (WW3) model coupled to a modified version of the National Centers for Environmental Prediction (NCEP) Climate Forecast System, version 2 (CFSv2). In this paper, we present results on the effect of the Madden Julian Oscillation (MJO) events and El Niño and the Southern Oscillation (ENSO) on such predictions. Forecasts initialized with multiple ocean analyses in both January and May for 1979-2008 are evaluated. A significant anomaly correlation of predicted and observed SWH anomalies (SWHA) at 3 weeks lead-time is found over portions of the domain in both January and May cases. The model successfully predicts almost all the important features of the observed SWHA during El Niño events in January, including negative SWHA in the central Indian Ocean and northern western tropical Pacific, and positive SWHA over the southern Ocean and western Pacific. The model also reproduces the spatial pattern of the inverse relationship between SWHA and sea level pressure anomalies during both composite El Niño and La Niña events at 3 weeks lead-time. The model successfully predicts the sign and magnitude of SWHA in May over the Bay of Bengal and South China Sea in composites of phases 2 and 6 of MJO. The observed leading mode of SWHA in May and the third mode of SWHA in January are influenced by the combined effects of MJO and ENSO. Analysis of the mechanisms for these relationships is described.

DNA reactivity as a mode of action and its relevance to cancer risk assessment.

PubMed

Preston, R Julian

2013-02-01

The ability of a chemical to induce mutations has long been a driver in the cancer risk assessment process. The default strategy has been that mutagenic chemicals demonstrate linear cancer dose responses, especially at low exposure levels. In the absence of additional confounding information, this is a reasonable approach, because risk assessment is appropriately considered as being protective of human health. The concept of mode of action has allowed for an opportunity to move off this default position; mutagenicity is now not considered as the driver but rather the mode of action is. In a more precise way, it is the set of key events that define a mode of action that is fundamental in defining the shape of a cancer dose response. A key event is an informative bioindicator of the cancer response and as such should be predictive of the tumor response, at least in a qualitative way. A clear example of the use of key events in cancer risk assessment is for DNA reactive chemicals. A series of such key events is initiated by the production of DNA damage in target cells from direct interaction of the chemical with DNA leading to the production of mutations by misreplication that results in enhanced cell replication. This enhanced cell replication eventually leads to the development of preneoplastic cells and ultimately overt neoplasms. The response of each of these key events to dose of the chemical can inform the cancer dose-response curve shape. Thus, the dose-response curve for any DNA-reactive chemical can be predicted from knowledge of its mode of action and the behavior of the induced key events.

A viscoplastic shear-zone model for deep (15-50 km) slow-slip events at plate convergent margins

NASA Astrophysics Data System (ADS)

Yin, An; Xie, Zhoumin; Meng, Lingsen

2018-06-01

A key issue in understanding the physics of deep (15-50 km) slow-slip events (D-SSE) at plate convergent margins is how their initially unstable motion becomes stabilized. Here we address this issue by quantifying a rate-strengthening mechanism using a viscoplastic shear-zone model inspired by recent advances in field observations and laboratory experiments. The well-established segmentation of slip modes in the downdip direction of a subduction shear zone allows discretization of an interseismic forearc system into the (1) frontal segment bounded by an interseismically locked megathrust, (2) middle segment bounded by episodically locked and unlocked viscoplastic shear zone, and (3) interior segment that slips freely. The three segments are assumed to be linked laterally by two springs that tighten with time, and the increasing elastic stress due to spring tightening eventually leads to plastic failure and initial viscous shear. This simplification leads to seven key model parameters that dictate a wide range of mechanical behaviors of an idealized convergent margin. Specifically, the viscoplastic rheology requires the initially unstable sliding to be terminated nearly instantaneously at a characteristic velocity, which is followed by stable sliding (i.e., slow-slip). The characteristic velocity, which is on the order of <10-7 m/s for the convergent margins examined in this study, depends on the (1) effective coefficient of friction, (2) thickness, (3) depth, and (4) viscosity of the viscoplastic shear zone. As viscosity decreases exponentially with temperature, our model predicts faster slow-slip rates, shorter slow-slip durations, more frequent slow-slip occurrences, and larger slow-slip magnitudes at warmer convergent margins.

Effect of initial conditions and of intra-event rainfall intensity variability on shallow landslide triggering return period

NASA Astrophysics Data System (ADS)

Peres, David Johnny; Cancelliere, Antonino

2016-04-01

Assessment of shallow landslide hazard is important for appropriate planning of mitigation measures. Generally, return period of slope instability is assumed as a quantitative metric to map landslide triggering hazard on a catchment. The most commonly applied approach to estimate such return period consists in coupling a physically-based landslide triggering model (hydrological and slope stability) with rainfall intensity-duration-frequency (IDF) curves. Among the drawbacks of such an approach, the following assumptions may be mentioned: (1) prefixed initial conditions, with no regard to their probability of occurrence, and (2) constant intensity-hyetographs. In our work we propose the use of a Monte Carlo simulation approach in order to investigate the effects of the two above mentioned assumptions. The approach is based on coupling a physically based hydrological and slope stability model with a stochastic rainfall time series generator. By this methodology a long series of synthetic rainfall data can be generated and given as input to a landslide triggering physically based model, in order to compute the return period of landslide triggering as the mean inter-arrival time of a factor of safety less than one. In particular, we couple the Neyman-Scott rectangular pulses model for hourly rainfall generation and the TRIGRS v.2 unsaturated model for the computation of transient response to individual rainfall events. Initial conditions are computed by a water table recession model that links initial conditions at a given event to the final response at the preceding event, thus taking into account variable inter-arrival time between storms. One-thousand years of synthetic hourly rainfall are generated to estimate return periods up to 100 years. Applications are first carried out to map landslide triggering hazard in the Loco catchment, located in highly landslide-prone area of the Peloritani Mountains, Sicily, Italy. Then a set of additional simulations are performed in order to compare the results obtained by the traditional IDF-based method with the Monte Carlo ones. Results indicate that both variability of initial conditions and of intra-event rainfall intensity significantly affect return period estimation. In particular, the common assumption of an initial water table depth at the base of the pervious strata may lead in practice to an overestimation of return period up to one order of magnitude, while the assumption of constant-intensity hyetographs may yield an overestimation by a factor of two or three. Hence, it may be concluded that the analysed simplifications involved in the traditional IDF-based approach generally imply a non-conservative assessment of landslide triggering hazard.

A mitocentric view of Alzheimer's disease suggests multi-faceted treatments.

PubMed

Gibson, Gary E; Shi, Qingli

2010-01-01

Alzheimer's disease (AD) is defined by senile plaques made of amyloid-beta peptide (Abeta), neurofibrillary tangles made of hyperphosphorylated tau proteins, and memory deficits. Thus, the events initiating the cascade leading to these end points may be more effective therapeutic targets than treating each facet individually. In the small percentage of cases of AD that are genetic (or animal models that reflect this form of AD), the factor initiating AD is clear (e.g., genetic mutations lead to high Abeta1-42 or hyperphosphorylated tau proteins). In the vast majority of AD cases, the cause is unknown. Substantial evidence now suggests that abnormalities in glucose metabolism/mitochondrial function/oxidative stress (GMO) are an invariant feature of AD and occur at an early stage of the disease process in both genetic and non-genetic forms of AD. Indeed, decreases in brain glucose utilization are diagnostic for AD. Changes in calcium homeostasis also precede clinical manifestations of AD. Abnormal GMO can lead to plaques, tangles, and the calcium abnormalities that accompany AD. Abnormalities in GMO diminish the ability of the brain to adapt. Therapies targeting mitochondria may ameliorate abnormalities in plaques, tangles, calcium homeostasis, and cognition that comprise AD.

Addison's disease.

PubMed

Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar

2012-10-01

Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered.

Addison's disease

PubMed Central

Sarkar, Soumya Brata; Sarkar, Subrata; Ghosh, Supratim; Bandyopadhyay, Subhankar

2012-01-01

Addison's disease is a rare endocrinal disorder, with several oral and systemic manifestations. A variety of pathological processes may cause Addison's disease. Classically, hyperpigmentation is associated with the disease, and intraoral pigmentation is perceived as the initial sign and develops earlier than the dermatological pigmentation. The symptoms of the disease usually progress slowly and an event of illness or accident can make the condition worse and may lead to a life-threatening crisis. In this case, several oral as well as systemic manifestation of the Addison's disease was encountered. PMID:23633816

Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

DTIC Science & Technology

2011-02-01

Thrombocytopenia, Grade 3 in 1 patient • Hypomagnesemia, Grade 3 in 1 patient • Hypokalemia, Grade 3 in 2 patient • Pneumonia , Grade 3 in 7 patients...urgently needed. While the molecular events involved in lung cancer pathogenesis are being unraveled by ongoing large scale genomics, proteomics, and...tumor initiation, progression and metastasis are an important first step leading to the development of new prognostic markers and targets for therapy

FREQUENCY OF TRAUMA EXPOSURE AND POST-TRAUMATIC STRESS DISORDERS IN ITALY: ANALYSIS FROM THE WORLD MENTAL HEALTH SURVEY INITIATIVE

PubMed Central

Carmassi, Claudia; Dell’Osso, Liliana; Manni, Corrado; Candini, Valentina; Dagani, Jessica; Iozzino, Laura; Koenen, Karestan C.; de Girolamo, Giovanni

2015-01-01

Epidemiological studies have examined the relative importance of Traumatic Events (TEs) in accounting for the societal burden of post-traumatic stress disorder (PTSD). However, most studies used the worst trauma experienced, which can lead to an overestimation of the conditional risk of PTSD. Although a number of epidemiological surveys on PTSD have been carried out in the United States, only a few studies in limited sample have been conducted in Italy. This study, carried out in the framework of the World Mental Health Survey Initiative, is a cross-sectional household survey of a representative sample of the Italian adult population. Lifetime prevalence of traumatic events (TEs) and 12-month prevalence of PTSD were evaluated using the Composite International Diagnostic Interview (CIDI). Reports of PTSD associated with randomly selected TEs were weighted by the individual-level probabilities of TE selection to generate estimates of population-level PTSD risk associated with each TE. Network events was the most commonly reported TE (29.4%). War events had the highest conditional risk of PTSD (12.2%). The TEs that contributed most to societal PTSD burden were unexpected death of a loved one (24.1%) and having seen atrocities (18.2%). Being female was related to high risk of PTSD after experiencing a TE. Exposure to network events is commonly reported among Italian adults, but two TE are responsible for the highest burden associated with PTSD: the unexpected death of someone close and sexual assault. These results can help designing public health interventions to reduce the societal PTSD burden. PMID:25266475

Developing and applying the adverse outcome pathway concept for understanding and predicting neurotoxicity

PubMed Central

Bal-Price, Anna; Lein, Pamela J.; Keil, Kimberly P.; Sethi, Sunjay; Shafer, Timothy; Barenys, Marta; Fritsche, Ellen; Sachana, Magdalini; Meek, M.E. (Bette)

2016-01-01

The Adverse Outcome Pathway (AOP) concept has recently been proposed to support a paradigm shift in regulatory toxicology testing and risk assessment. This concept is similar to the Mode of Action (MOA), in that it describes a sequence of measurable key events triggered by a molecular initiating event in which a stressor interacts with a biological target. The resulting cascade of key events includes molecular, cellular, structural and functional changes in biological systems, resulting in a measurable adverse outcome. Thereby, an AOP ideally provides information relevant to chemical structure-activity relationships as a basis for predicting effects of structurally similar compounds. AOPs could potentially also form the basis for qualitative and quantitative predictive modeling of the human adverse outcome resulting from molecular initiating or other key events for which higher-throughput testing methods are available or can be developed. A variety of cellular and molecular processes are known to be critical for normal function of the central (CNS) and peripheral nervous systems (PNS). Because of the biological and functional complexity of the CNS and PNS, it has been challenging to establish causative links and quantitative relationships between key events that comprise the pathways leading from chemical exposure to an adverse outcome in the nervous system. Following introduction of the principles of MOA and AOPs, examples of potential or putative adverse outcome pathways specific for developmental or adult neurotoxicity are summarized and aspects of their assessment considered. Their possible application in developing mechanistically informed Integrated Approaches to Testing and Assessment (IATA) is also discussed. PMID:27212452

Defining a Computational Framework for the Assessment of ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway (AOP) framework describes the effects of environmental stressors across multiple scales of biological organization and function. This includes an evaluation of the potential for each key event to occur across a broad range of species in order to determine the taxonomic applicability of each AOP. Computational tools are needed to facilitate this process. Recently, we developed a tool that uses sequence homology to evaluate the applicability of molecular initiating events across species (Lalone et al., Toxicol. Sci., 2016). To extend our ability to make computational predictions at higher levels of biological organization, we have created the AOPdb. This database links molecular targets identified associated with key events in the AOPwiki to publically available data (e.g. gene-protein, pathway, species orthology, ontology, chemical, disease) including ToxCast assay information. The AOPdb combines different data types in order to characterize the impacts of chemicals to human health and the environment and serves as a decision support tool for case study development in the area of taxonomic applicability. As a proof of concept, the AOPdb allows identification of relevant molecular targets, biological pathways, and chemical and disease associations across species for four AOPs from the AOP-Wiki (https://aopwiki.org): Estrogen receptor antagonism leading to reproductive dysfunction (Aop:30); Aromatase inhibition leading to reproductive d

The Modification of Orographic Snow Growth Processes by Cloud Nucleating Aerosols

NASA Astrophysics Data System (ADS)

Cotton, W. R.; Saleeby, S.

2011-12-01

Cloud nucleating aerosols have been found to modify the amount and spatial distribution of snowfall in mountainous areas where riming growth of snow crystals is known to contribute substantially to the total snow water equivalent precipitation. In the Park Range of Colorado, a 2km deep supercooled liquid water orographic cloud frequently enshrouds the mountaintop during snowfall events. This leads to a seeder-feeder growth regime in which snow falls through the orographic cloud and collects cloud water prior to surface deposition. The addition of higher concentrations of cloud condensation nuclei (CCN) modifies the cloud droplet spectrum toward smaller size droplets and suppresses riming growth. Without rime growth, the density of snow crystals remains low and horizontal trajectories carry them further downwind due to slower vertical fall speeds. This leads to a downwind shift in snowfall accumulation at high CCN concentrations. Cloud resolving model simulations were performed (at 600m horizontal grid spacing) for six snowfall events over the Park Range. The chosen events were well simulated and occurred during intensive observations periods as part of two winter field campaigns in 2007 and 2010 based at Storm Peak Laboratory in Steamboat Springs, CO. For each event, sensitivity simulations were run with various initial CCN concentration vertical profiles that represent clean to polluted aerosol environments. Microphysical budget analyses were performed for these simulations in order to determine the relative importance of the various cloud properties and growth processes that contribute to precipitation production. Observations and modeling results indicate that initial vapor depositional growth of snow tends to be maximized within about 1km of mountaintop above the windward slope while the majority of riming growth occurs within 500m of mountaintop. This suggests that precipitation production is predominantly driven by locally enhanced orography. The large scale synoptic flow simply provides the background dynamics and moisture that impinge upon the steep terrain. The addition of cloud nucleating aerosols to this scenario tends to reduce the amount of riming and leads to greater snow vapor growth. Increased vapor growth leads to larger snow crystals but does not necessarily increase their density or fall speed. There is frequently a zone on the periphery of the orographic cloud where water saturation is low and ice saturation remains high. Here the Bergeron process allows for snow to continue growing at the expense of the cloud water. Furthermore, since less cloud water is removed by riming, and droplets are smaller in polluted conditions, there is an increase in cloud water evaporation along the lee slope. This enhanced droplet evaporation in polluted conditions allows for more saturated air to persist to the lee of the ridge. Higher saturation reduces the amount of snow crystal sublimation prior to surface deposition. In very moist winter events, the lee slope evaporation relative to the primary mountain barrier can saturate the air relative to a downstream ridge and aid in further orographic cloud development. The combination of reduced riming, the Bergeron process, and reduced lee-side sublimation leads to the snowfall spillover effect under polluted conditions.

The initiation of metabolic inflammation in childhood obesity.

PubMed

Singer, Kanakadurga; Lumeng, Carey N

2017-01-03

An understanding of the events that initiate metabolic inflammation (metainflammation) can support the identification of targets for preventing metabolic disease and its negative effects on health. There is ample evidence demonstrating that the initiating events in obesity-induced inflammation start early in childhood. This has significant implications on our understanding of how early life events in childhood influence adult disease. In this Review we frame the initiating events of metainflammation in the context of child development and discuss what this reveals about the mechanisms by which this unique form of chronic inflammation is initiated and sustained into adulthood.

The initiation of metabolic inflammation in childhood obesity

PubMed Central

2017-01-01

An understanding of the events that initiate metabolic inflammation (metainflammation) can support the identification of targets for preventing metabolic disease and its negative effects on health. There is ample evidence demonstrating that the initiating events in obesity-induced inflammation start early in childhood. This has significant implications on our understanding of how early life events in childhood influence adult disease. In this Review we frame the initiating events of metainflammation in the context of child development and discuss what this reveals about the mechanisms by which this unique form of chronic inflammation is initiated and sustained into adulthood. PMID:28045405

Effect of Medicare's nonpayment for Hospital-Acquired Conditions: lessons for future policy.

PubMed

Waters, Teresa M; Daniels, Michael J; Bazzoli, Gloria J; Perencevich, Eli; Dunton, Nancy; Staggs, Vincent S; Potter, Catima; Fareed, Naleef; Liu, Minzhao; Shorr, Ronald I

2015-03-01

In 2008, Medicare implemented the Hospital-Acquired Conditions (HACs) Initiative, a policy denying incremental payment for 8 complications of hospital care, also known as never events. The regulation's effect on these events has not been well studied. To measure the association between Medicare's nonpayment policy and 4 outcomes addressed by the HACs Initiative: central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), hospital-acquired pressure ulcers (HAPUs), and injurious inpatient falls. Quasi-experimental study of adult nursing units from 1381 US hospitals participating in the National Database of Nursing Quality Indicators (NDNQI), a program of the American Nurses Association. The NDNQI data were combined with American Hospital Association, Medicare Cost Report, and local market data to examine adjusted outcomes. Multilevel models were used to evaluate the effect of Medicare's nonpayment policy on never events. United States hospitals providing treatment for Medicare patients were subject to the new payment policy beginning in October 2008. Changes in unit-level rates of HAPUs, injurious falls, CLABSIs, and CAUTIs after initiation of the policy. Medicare's nonpayment policy was associated with an 11% reduction in the rate of change in CLABSIs (incidence rate ratio [IRR], 0.89; 95% CI, 0.83-0.95) and a 10% reduction in the rate of change in CAUTIs (IRR, 0.90; 95% CI, 0.85-0.95), but was not associated with a significant change in injurious falls (IRR, 0.99; 95% CI, 0.99-1.00) or HAPUs (odds ratio, 0.98; 95% CI, 0.96-1.01). Consideration of unit-, hospital-, and market-level factors did not significantly alter our findings. The HACs Initiative was associated with improvements in CLABSI and CAUTI trends, conditions for which there is strong evidence that better hospital processes yield better outcomes. However, the HACs Initiative was not associated with improvements in HAPU or injurious fall trends, conditions for which there is less evidence that changing hospital processes leads to significantly better outcomes.

Testing the sulfate-phosphorous hypothesis for initiation of the early Aptian OAE1a

NASA Astrophysics Data System (ADS)

Mills, J. V.; Gomes, M. L.; Sageman, B. B.; Hurtgen, M. T.

2012-12-01

Oceanic anoxic events (OAEs) were short-lived (<1-myr) episodes of widespread marine organic carbon burial and anoxia that occurred during the Mesozoic. Several hypotheses have been proposed to explain these intervals of increased organic carbon production and preservation, yet none have satisfactorily accounted for the short-term character and widespread effects of the events. Some recent work has focused on the role of sulfur in the initiation/termination mechanism of these events, specifically the potential impact of a large increase in marine sulfate levels upon a very low sulfate background. Previous authors have suggested that a large pulse of volcanic-derived sulfur could have initiated widespread anoxia through a positive feedback cycle of enhanced phosphorous recycling and increased primary production. In this model, a sudden pulse of sulfur upon a low sulfate background impacts the biogeochemical cycles of sulfur and iron, leading to an escalation in phosphorous (P) release from sediments during organic matter degradation. The resulting sulfate-P feedback cycle, recognized in modern lake systems, continues until sulfate levels are drawn down by pyrite burial, thus ending the anoxic event. To test this hypothesis, we examine sulfur and carbon isotopes through the early Aptian OAE1a (~120 Ma) from Resolution Guyot in the Mid-Pacific Mountains (ODP Site 866). We present sulfur isotope records of carbonate-associated sulfate (CAS), which provide a higher resolution record than other sulfate records (e.g. marine barites), to infer how sulfate concentrations changed through the event. A decrease of ~5 permil in the CAS sulfur isotope composition through the event suggests either that massive volcanism delivered 34S-depleted sulfate to the oceans and/or that large-scale evaporite (calcium sulfate) deposition forced a reduction in marine sulfate levels and associated rates of pyrite burial. These results will be discussed within the context of evolving δ34Spyrite values in order to better constrain the evolution of marine sulfate concentrations through this time period and evaluate the importance of the sulfate-P feedback mechanism in regulating OAE1a.

Talking Climate Science in a Changing Media Landscape

NASA Astrophysics Data System (ADS)

Cullen, H. M.

2014-12-01

Founded in 2008 by leading scientists and communications experts at Princeton, Yale and Stanford, Climate Central brings together award-winning journalists and internationally recognized scientists to report the science and impacts of climate change through its research and journalism programs. Climate Central works to tackle the misperception that climate change is a distant thing - affecting other people and other places - by demonstrating the local and personal impacts of global warming. This talk will focus on describing three important Climate Central initiatives. First, our Climate Matters program delivers localized climate information at the regional and local level to weathercasters around the U.S., providing ready-to-use, broadcast quality graphics and analyses that put climate change in a local context. After three years, the program has grown from a pilot with just one TV meteorologist in Columbia, South Carolina to a network of more than 150 weathercasters across the country. Climate Central was also closely involved in the development and production of Years of Living Dangerously - a 9-part global warming documentary that premiered in April 2014. Finally, the World Weather Attribution project is a new initiative that aims to identify the human fingerprint in certain types of extreme weather events, including sea level rise and its contribution to storm surges, extreme heat events, heavy rainfall events/flooding, and drought. Our goal is to objectively and transparently assess certain extreme events and equip journalists and scientists with the tools to provide the larger global warming context in real-time while there is still media interest.

Constraining fault constitutive behavior with slip and stress heterogeneity

USGS Publications Warehouse

Aagaard, Brad T.; Heaton, T.H.

2008-01-01

We study how enforcing self-consistency in the statistical properties of the preshear and postshear stress on a fault can be used to constrain fault constitutive behavior beyond that required to produce a desired spatial and temporal evolution of slip in a single event. We explore features of rupture dynamics that (1) lead to slip heterogeneity in earthquake ruptures and (2) maintain these conditions following rupture, so that the stress field is compatible with the generation of aftershocks and facilitates heterogeneous slip in subsequent events. Our three-dimensional fmite element simulations of magnitude 7 events on a vertical, planar strike-slip fault show that the conditions that lead to slip heterogeneity remain in place after large events when the dynamic stress drop (initial shear stress) and breakdown work (fracture energy) are spatially heterogeneous. In these models the breakdown work is on the order of MJ/m2, which is comparable to the radiated energy. These conditions producing slip heterogeneity also tend to produce narrower slip pulses independent of a slip rate dependence in the fault constitutive model. An alternative mechanism for generating these confined slip pulses appears to be fault constitutive models that have a stronger rate dependence, which also makes them difficult to implement in numerical models. We hypothesize that self-consistent ruptures could also be produced by very narrow slip pulses propagating in a self-sustaining heterogeneous stress field with breakdown work comparable to fracture energy estimates of kJ/M2. Copyright 2008 by the American Geophysical Union.

Spatio-Temporal b Value Trends For a PMMA-PMMA Frictional Interface

NASA Astrophysics Data System (ADS)

Parker, J.; Selvadurai, P. A.; Glaser, S. D.

2016-12-01

We develop a catalog of seismic events observed on a well-characterized PMMA-PMMA frictional interface to allow for an in depth study of spatio-temporal trends in along-fault b values. Recent studies of the 2009 L'Aquila [Gulia et al., GRL, 2016] and 2011 Tohoku-oki [Tormann et al., Nature Geo., 2015] events have found significant decrease in b values near the epicenters in the months leading up to rupture. Here, a fault is experimentally modeled using two Poly(methyl methacrylate) samples in a direct shear configuration. The initial, non-uniform distribution of asperities along the frictional interface was measured using a pressure sensitive film. Prior to a stick-slip event, localized seismicity was captured using 16 acoustic emission (AE) sensors, which provide the catalog events and b value analysis. We observe similar decreasing trends in b values prior to failure as observed in nature. We discuss the spatio-temporal variations in b values with respect to a slowly expanding shear rupture captured using dense `along-strike' arrays of 9 slip sensors and 24 strain gauges. The rate at which the shear rupture moved along the interface depended on the shear strength heterogeneity characterized by the non-uniform distribution of asperities. In the latter stages of nucleation, b values decrease primarily in a region with larger and more densely distributed asperities. The combined analysis will help confirm recent field observations and provide insight into the mechanics of foreshock sequences leading to earthquake rupture.

Development and Testing of Operational Dual-Polarimetric Radar Based Lightning Initiation Forecast Techniques

NASA Technical Reports Server (NTRS)

Woodard, Crystal; Carey, Lawrence D.; Petersen, Walter A.; Felix, Mariana; Roeder, William P.

2011-01-01

Lightning is one of Earth s natural dangers, destructive not only to life but also physical property. According to the National Weather Service, there are on average 58 lightning fatalities each year, with over 300 related injuries (NWS 2010). The ability to forecast lightning is critical to a host of activities ranging from space vehicle launch operations to recreational sporting events. For example a single lightning strike to a Space Shuttle could cause billions of dollars of damage and possible loss of life. While forecasting that provides longer lead times could provide sporting officials with more time to respond to possible threatening weather events, thus saving the lives of player and bystanders. Many researchers have developed and tested different methods and tools of first flash forecasting, however few have done so using dual-polarimetric radar variables and products on an operational basis. The purpose of this study is to improve algorithms for the short-term prediction of lightning initiation through development and testing of operational techniques that rely on parameters observed and diagnosed using C-band dual-polarimetric radar.

Ontogeny of the Human Pelvis.

PubMed

Verbruggen, Stefaan W; Nowlan, Niamh C

2017-04-01

The human pelvis has evolved over time into a remarkable structure, optimised into an intricate architecture that transfers the entire load of the upper body into the lower limbs, while also facilitating bipedal movement. The pelvic girdle is composed of two hip bones, os coxae, themselves each formed from the gradual fusion of the ischium, ilium and pubis bones. Unlike the development of the classical long bones, a complex timeline of events must occur in order for the pelvis to arise from the embryonic limb buds. An initial blastemal structure forms from the mesenchyme, with chondrification of this mass leading to the first recognisable elements of the pelvis. Primary ossification centres initiate in utero, followed post-natally by secondary ossification at a range of locations, with these processes not complete until adulthood. This cascade of events can vary between individuals, with recent evidence suggesting that fetal activity can affect the normal development of the pelvis. This review surveys the current literature on the ontogeny of the human pelvis. Anat Rec, 300:643-652, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Numerical simulations of catastrophic disruption: Recent results

NASA Technical Reports Server (NTRS)

Benz, W.; Asphaug, E.; Ryan, E. V.

1994-01-01

Numerical simulations have been used to study high velocity two-body impacts. In this paper, a two-dimensional Largrangian finite difference hydro-code and a three-dimensional smooth particle hydro-code (SPH) are described and initial results reported. These codes can be, and have been, used to make specific predictions about particular objects in our solar system. But more significantly, they allow us to explore a broad range of collisional events. Certain parameters (size, time) can be studied only over a very restricted range within the laboratory; other parameters (initial spin, low gravity, exotic structure or composition) are difficult to study at all experimentally. The outcomes of numerical simulations lead to a more general and accurate understanding of impacts in their many forms.

An experimental study of compression failure of fibrous laminated composites in the presence of stress gradients

NASA Technical Reports Server (NTRS)

Waas, A. M.; Knauss, W. G.; Babcock, C. D., Jr.

1990-01-01

Mechanisms of failure in laminates in the presence of a stress raiser were experimentally studied. The damage initiation and propagation throughout the entire load history were examined via real-time holographic interferometry and photomicrography of the hole surface. Multilayered composite flat plates made of T300/BP907 and IM7/8551-7 were tested. It is shown that the failure is initiated as a localized instability in the 0-deg plies at the hole surface approximately at right angles to the loading direction. A series of events is described which culminates in the complete loss of flexural stiffness of each of the delaminated portions, leading to catastrophic failure of the plate.

Can test fields destroy the event horizon in the Kerr–Taub–NUT spacetime?

NASA Astrophysics Data System (ADS)

Düztaş, Koray

2018-02-01

In this work we investigate if the interaction of the Kerr–Taub–NUT spacetime with test scalar and neutrino fields can lead to the destruction of the event horizon. It turns out that both extremal and nearly extremal black holes can be destroyed by scalar and neutrino fields if the initial angular momentum of the spacetime is sufficiently large relative to its mass and NUT charge. This is the first example in which a classical field satisfying the null energy condition can actually destroy an extremal black hole. For scalar fields, the modes that can lead to the destruction of the horizon are restricted to a narrow range due to superradiance. Since superradiance does not occur for neutrino fields, the destruction of the horizon by neutrino fields is generic, and it cannot be fixed by backreaction effects. We also show that the extremal black holes that can be destroyed by scalar fields correspond to naked singularities in the Kerr limit, in accord with the previous results which imply that extremal Kerr black holes cannot be destroyed by scalar test fields.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarrack, A.G.

The purpose of this report is to document fault tree analyses which have been completed for the Defense Waste Processing Facility (DWPF) safety analysis. Logic models for equipment failures and human error combinations that could lead to flammable gas explosions in various process tanks, or failure of critical support systems were developed for internal initiating events and for earthquakes. These fault trees provide frequency estimates for support systems failures and accidents that could lead to radioactive and hazardous chemical releases both on-site and off-site. Top event frequency results from these fault trees will be used in further APET analyses tomore » calculate accident risk associated with DWPF facility operations. This report lists and explains important underlying assumptions, provides references for failure data sources, and briefly describes the fault tree method used. Specific commitments from DWPF to provide new procedural/administrative controls or system design changes are listed in the ''Facility Commitments'' section. The purpose of the ''Assumptions'' section is to clarify the basis for fault tree modeling, and is not necessarily a list of items required to be protected by Technical Safety Requirements (TSRs).« less

Phototropism: translating light into directional growth.

PubMed

Hohm, Tim; Preuten, Tobias; Fankhauser, Christian

2013-01-01

Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

Thin-Film Module Reverse-Bias Breakdown Sites Identified by Thermal Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, Steven; Sulas, Dana; Guthrey, Harvey L

Thin-film module sections are stressed under reverse bias to simulate partial shading conditions. Such stresses can cause permanent damage in the form of 'wormlike' defects due to thermal runaway. When large reverse biases with limited current are applied to the cells, dark lock-in thermography (DLIT) can detect where spatially-localized breakdown initiates before thermal runaway leads to permanent damage. Predicted breakdown defect sites have been identified in both CIGS and CdTe modules using DLIT. These defects include small pinholes, craters, or voids in the absorber layer of the film that lead to built-in areas of weakness where high current densities maymore » cause thermal damage in a partial-shading event.« less

From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis.

PubMed

Usman, Ammara; Ribatti, Domenico; Sadat, Umar; Gillard, Jonathan H

2015-08-26

Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed.

Electrocardiographic predictors of adverse cardiovascular events in suspected poisoning.

PubMed

Manini, Alex F; Nelson, Lewis S; Skolnick, Adam H; Slater, William; Hoffman, Robert S

2010-06-01

Poisoning is the second leading cause of injury-related fatality in the USA and the leading cause of cardiac arrest in victims under 40 years of age. The study objective was to define the electrocardiographic (ECG) predictors of adverse cardiovascular events (ACVE) complicating suspected acute poisoning (SAP). This was a case-control study in adults at three tertiary-care hospitals and one regional Poison Control Center. We compared 34 cases of SAP complicated by ACVE to 101 consecutive control patients with uncomplicated SAP. The initial ECG was analyzed for rhythm, intervals, QT dispersion, ischemia, and infarction. ECGs were interpreted by a cardiologist, blinded to study hypothesis and case data. Subjects were 48% male, with mean age 42 +/- 19 years. In addition to clinical suspicion of poisoning in 100% of patients, routine toxicology screens were positive in 77%, most commonly for benzodiazepines, opioids, and/or acetaminophen. Neither the ventricular rate, the QRS duration, nor the presence of infarction predicted the risk of ACVE. However, the rhythm, QTc, QT dispersion, and presence of ischemia correlated with the risk of ACVE. Independent predictors of ACVE based on multivariable logistic regression were prolonged QTc, any non-sinus rhythm, ventricular ectopy, and ischemia. Recursive partitioning analysis identified very low risk criteria (94.1% sensitivity, 96.2% NPV) and high risk criteria (95% specificity). Among patients with SAP, the presence of QTc prolongation, QT dispersion, ventricular ectopy, any non-sinus rhythm, and evidence of ischemia on the initial ECG are strongly associated with ACVE.

The Evolving Field of Human Papillomavirus Receptor Research: a Review of Binding and Entry

PubMed Central

Raff, Adam B.; Woodham, Andrew W.; Raff, Laura M.; Skeate, Joseph G.; Yan, Lisa; Da Silva, Diane M.; Schelhaas, Mario

2013-01-01

Human papillomaviruses (HPVs) infect epithelia and can lead to the development of lesions, some of which have malignant potential. HPV type 16 (HPV16) is the most oncogenic genotype and causes various types of cancer, including cervical, anal, and head and neck cancers. However, despite significant research, our understanding of the mechanism by which HPV16 binds to and enters host cells remains fragmented. Over several decades, many HPV receptors and entry pathways have been described. This review puts those studies into context and offers a model of HPV16 binding and entry as a framework for future research. Our model suggests that HPV16 binds to heparin sulfate proteoglycans (HSPGs) on either the epithelial cell surface or basement membrane through interactions with the L1 major capsid protein. Growth factor receptors may also become activated through HSPG/growth factor/HPV16 complexes that initiate signaling cascades during early virion-host cell interactions. After binding to HSPGs, the virion undergoes conformational changes, leading to isomerization by cyclophilin B and proprotein convertase-mediated L2 minor capsid protein cleavage that increases L2 N terminus exposure. Along with binding to HSPGs, HPV16 binds to α6 integrins, which initiate further intracellular signaling events. Following these primary binding events, HPV16 binds to a newly identified L2-specific receptor, the annexin A2 heterotetramer. Subsequently, clathrin-, caveolin-, lipid raft-, flotillin-, cholesterol-, and dynamin-independent endocytosis of HPV16 occurs. PMID:23536685

Why natural disaster planning scenarios are often so disastrously wrong.

NASA Astrophysics Data System (ADS)

Verosub, K. L.

2017-12-01

Taken together the four hurricanes that impacted the United States in the summer of 2017 demonstrate the difficulties involved in trying to plan for any natural disaster, not simply a major hurricane. They also highlight the extraordinary degree to which small and/or random variations in initial conditions can have enormous consequences on the outcome of an event and on the ability of a society to respond to it. For example, if Harvey had been moving faster, it would have meant less rainfall and hence less flooding in the Houston area whereas a slight change in the path of Irma would have significantly affected which portions of the Florida peninsula would have experienced greater or lesser devastation. In the case of Marie, hurricane intensity and path as well as the terrain in Puerto Rico and the inherent state of its infrastructure greatly complicated relief and recovery efforts there. An additional factor that makes planning scenarios so difficult to develop is that major natural disasters can often be analyzed as a sequence of events. At each juncture in the sequence, the event might evolve along two or more very different pathways, which can lead to different outcomes. Sometimes, as with Nate, an event evolves more or less "as expected" and the planning scenario does what it was supposed to do, namely, help people respond to the event. But to a much greater extent than is usually recognized, small or random variations can drive an event off its expected trajectory and into a response realm that "no one could have foreseen." Even worse is when those small or random variations allow an event to bifurcate and follow two or more different pathways simultaneously, leading to a cascading disaster that totally overwhelms whatever planning and preparation has been put in place. Perhaps the main lessons to be learned from these storms is that planning for any disaster requires greater recognition of the importance of small or random factors and greater appreciation of the complexity of these events. One plan or one model scenario does not provide adequate preparation for all events of a particular type and is probably unlikely to provide adequate preparation for any single given event.

Initialization shock in decadal hindcasts due to errors in wind stress over the tropical Pacific

NASA Astrophysics Data System (ADS)

Pohlmann, Holger; Kröger, Jürgen; Greatbatch, Richard J.; Müller, Wolfgang A.

2017-10-01

Low prediction skill in the tropical Pacific is a common problem in decadal prediction systems, especially for lead years 2-5 which, in many systems, is lower than in uninitialized experiments. On the other hand, the tropical Pacific is of almost worldwide climate relevance through its teleconnections with other tropical and extratropical regions and also of importance for global mean temperature. Understanding the causes of the reduced prediction skill is thus of major interest for decadal climate predictions. We look into the problem of reduced prediction skill by analyzing the Max Planck Institute Earth System Model (MPI-ESM) decadal hindcasts for the fifth phase of the Climate Model Intercomparison Project and performing a sensitivity experiment in which hindcasts are initialized from a model run forced only by surface wind stress. In both systems, sea surface temperature variability in the tropical Pacific is successfully initialized, but most skill is lost at lead years 2-5. Utilizing the sensitivity experiment enables us to pin down the reason for the reduced prediction skill in MPI-ESM to errors in wind stress used for the initialization. A spurious trend in the wind stress forcing displaces the equatorial thermocline in MPI-ESM unrealistically. When the climate model is then switched into its forecast mode, the recovery process triggers artificial El Niño and La Niña events at the surface. Our results demonstrate the importance of realistic wind stress products for the initialization of decadal predictions.

Initiating Event Analysis of a Lithium Fluoride Thorium Reactor

NASA Astrophysics Data System (ADS)

Geraci, Nicholas Charles

The primary purpose of this study is to perform an Initiating Event Analysis for a Lithium Fluoride Thorium Reactor (LFTR) as the first step of a Probabilistic Safety Assessment (PSA). The major objective of the research is to compile a list of key initiating events capable of resulting in failure of safety systems and release of radioactive material from the LFTR. Due to the complex interactions between engineering design, component reliability and human reliability, probabilistic safety assessments are most useful when the scope is limited to a single reactor plant. Thus, this thesis will study the LFTR design proposed by Flibe Energy. An October 2015 Electric Power Research Institute report on the Flibe Energy LFTR asked "what-if?" questions of subject matter experts and compiled a list of key hazards with the most significant consequences to the safety or integrity of the LFTR. The potential exists for unforeseen hazards to pose additional risk for the LFTR, but the scope of this thesis is limited to evaluation of those key hazards already identified by Flibe Energy. These key hazards are the starting point for the Initiating Event Analysis performed in this thesis. Engineering evaluation and technical study of the plant using a literature review and comparison to reference technology revealed four hazards with high potential to cause reactor core damage. To determine the initiating events resulting in realization of these four hazards, reference was made to previous PSAs and existing NRC and EPRI initiating event lists. Finally, fault tree and event tree analyses were conducted, completing the logical classification of initiating events. Results are qualitative as opposed to quantitative due to the early stages of system design descriptions and lack of operating experience or data for the LFTR. In summary, this thesis analyzes initiating events using previous research and inductive and deductive reasoning through traditional risk management techniques to arrive at a list of key initiating events that can be used to address vulnerabilities during the design phases of LFTR development.

Using SDO Data in the Classroom to Do Real Science -- A Community College Laboratory Investigation

NASA Astrophysics Data System (ADS)

Dave, T. A.; Hildreth, S.; Lee, S.; Scherrer, D. K.

2013-12-01

The incredible accessibility of extremely high spatial and temporal resolution data from the Solar Dynamics Observatory creates an opportunity for students to do almost real-time investigation in an Astronomy Lab. We are developing a short series of laboratory exercises using SDO data, targeted for Community College students in an introductory lab class, extendable to high school and university students. The labs initially lead students to explore what SDO can do, online, through existing SDO video clips taken on specific dates. Students then investigate solar events using the Heliophysics Events Knowledgebase (HEK), and make their own online movies of events, to discuss and share with classmates. Finally, students can investigate specific events and areas, selecting specific dates, locations, wavelength regions, and time cadences to create and gather their own SDO datasets for more detailed investigation. In exploring the Sun using actual data, students actually do real science. We are in the process of beta testing the sequence of labs, and are seeking interested community college, university, and high school astronomy lab teachers who might consider trying the labs themselves.

Solar Flare Super-Events: When they Can Occur and the Energy Limits of their Realization

NASA Astrophysics Data System (ADS)

Ishkov, Vitaly N.

2015-03-01

For the successful development of terrestrial civilization it is necessary to estimate the space factors, including phenomena on Sun, which can ruin it or cause such catastrophic loss, that the restoration to the initial level can take unacceptably long time. Super-powerful solar flares are the only such phenomena. Therefore an attempt is undertaken to estimate the possibility of such super-event occurrence at this stage of our star evolution. Since solar flare events are the consequence of the newly emerging magnetic fluxes interacting with the already existing magnetic fields of active regions, are investigated the observed cases which lead to the realization of such super-events. From the observations of the maximal magnetic fluxes during the period of reliable solar observations, the conclusion is made that the super- extreme solar flares cannot significantly exceed the most powerful solar flares which have already been observed. On the statistics of the reliable solar cycles the sunspot groups, in which occurred the most powerful solar super-events (August- September 1859 - solar cycle 10; June 1991 - SC 22; October-November 2003 - SC 23) appeared in the periods of the solar magnetic field reorganization between the epochs of "increased" and "lowered" solar activity.

Extended-range ensemble forecasting of tropical cyclogenesis in the northern Indian Ocean: Modulation of Madden-Julian Oscillation

NASA Astrophysics Data System (ADS)

Fu, Xiouhua; Hsu, Pang-chi

2011-08-01

A conventional atmosphere-ocean coupled system initialized with NCEP FNL analysis has successfully predicted a tropical cyclogenesis event in the northern Indian Ocean with a lead time of two weeks. The coupled forecasting system reproduces the westerly wind bursts in the equatorial Indian Ocean associated with an eastward-propagating Madden-Julian Oscillation (MJO) event as well as the accompanying northward-propagating westerly and convective disturbances. After reaching the Bay of Bengal, this northward-propagating Intra-Seasonal Variability (ISV) fosters the tropical cyclogenesis. The present finding demonstrates that a realistic MJO/ISV prediction will make the extended-range forecasting of tropical cyclogenesis possible and also calls for improved representation of the MJO/ISV in contemporary weather and climate forecast models.

Lithium carbonate as a treatment for paliperidone extended-release-induced leukopenia and neutropenia in a patient with schizoaffective disorder; a case report.

PubMed

Matsuura, Hiroki; Kimoto, Sohei; Harada, Izumi; Naemura, Satoshi; Yamamuro, Kazuhiko; Kishimoto, Toshifumi

2016-05-26

Antipsychotic drug treatment can potentially lead to adverse events such as leukopenia and neutropenia. Although these events are rare, they represent serious and life-threatening hematological side effects. We present a case study of a patient with schizoaffective disorder in a 50-year-old woman. We report a case of paliperidone extended-release (ER)-induced leukopenia and neutropenia in a female patient with schizoaffective disorder. Initiating lithium carbonate treatment and decreasing the dose of valproic acid improved the observed leukopenia and neutropenia. This treatment did not influence psychotic symptoms. The combination of paliperidone ER and valproic acid induces increased paliperidone ER plasma levels. Lithium carbonate was successfully used to treat paliperidone ER-induced leukopenia and neutropenia.

Beyond Verb Meaning: Experimental Evidence for Incremental Processing of Semantic Roles and Event Structure.

PubMed

Philipp, Markus; Graf, Tim; Kretzschmar, Franziska; Primus, Beatrice

2017-01-01

We present an event-related potentials (ERP) study that addresses the question of how pieces of information pertaining to semantic roles and event structure interact with each other and with the verb's meaning. Specifically, our study investigates German verb-final clauses with verbs of motion such as fliegen 'fly' and schweben 'float, hover,' which are indeterminate with respect to agentivity and event structure. Agentivity was tested by manipulating the animacy of the subject noun phrase and event structure by selecting a goal adverbial, which makes the event telic, or a locative adverbial, which leads to an atelic reading. On the clause-initial subject, inanimates evoked an N400 effect vis-à-vis animates. On the adverbial phrase in the atelic (locative) condition, inanimates showed an N400 in comparison to animates. The telic (goal) condition exhibited a similar amplitude like the inanimate-atelic condition. Finally, at the verbal lexeme, the inanimate condition elicited an N400 effect against the animate condition in the telic (goal) contexts. In the atelic (locative) condition, items with animates evoked an N400 effect compared to inanimates. The combined set of findings suggest that clause-initial animacy is not sufficient for agent identification in German, which seems to be completed only at the verbal lexeme in our experiment. Here non-agents (inanimates) changing their location in a goal-directed way and agents (animates) lacking this property are dispreferred and this challenges the assumption that change of (locational) state is generally a defining characteristic of the patient role. Besides this main finding that sheds new light on role prototypicality, our data seem to indicate effects that, in our view, are related to complexity, i.e., minimality. Inanimate subjects or goal arguments increase processing costs since they have role or event structure restrictions that animate subjects or locative modifiers lack.

Climatological and meteorological conditions associated with rain-induced periglacial debris flows in the Cascade Range, USA

NASA Astrophysics Data System (ADS)

Parker, L.; Nolin, A. W.

2009-04-01

Title: Climatological and meteorological conditions associated with rain-induced periglacial debris flows in the Cascade Range, USA Authors: L. Parker, A.W. Nolin Affiliation: Department of Geosciences, Oregon State University, Corvallis, Oregon, USA In November of 2006 an intense rainstorm of tropical origin, known colloquially as "Pineapple Express," inundated the Pacific Northwest region of the United States, initiating numerous periglacial debris flows on several of the stratovolcanoes in the Cascade Range of Oregon and Washington. Rain-induced periglacial debris flows are the result of the over-saturation and subsequent collapse of steep moraine in formerly glaciated valleys. These debris flows rapidly aggrade channels, deposit thick sediments in their path, and severely damage infrastructure. Here we focus on Mount Hood, Oregon and Mount Rainier, Washington in the investigation of meteorological and climatological conditions surrounding rain-induced periglacial debris flow events and their variability over time. Both anecdotal and observational evidence suggest that the Pineapple Express storms are a likely triggering mechanism for these rain-induced debris flows on the stratovolcanoes. Dates for the debris flow events for each mountain were linked with corresponding Pineapple Express storm events. Preliminary analysis suggests that one or more particular climatological or meteorological conditions may be central to the initiation of debris flows, though these conditions may not always be present during Pineapple Express storms. Antecedent snowpack conditions are also hypothesized to play an important role in periglacial rain-induced debris flow initiation as the presence of snow cover on the moraines and glaciers is thought to reduce the likelihood of a debris flow. Radiosonde and precipitation data from Salem, Oregon (KSLE) and Quillayute, Washington (KUIL) data are used to determine if freezing levels and precipitation amounts have changed over time for all documented Pineapple Express events. Particular focus is placed on those events associated with debris flows. Additionally, Snowpack Telemetry (SNOTEL) data are used to examine the antecedent snowpack conditions for each debris flow event. These results will ultimately be coupled with research concerning the geomorphological mechanisms behind debris flows on stratovolcanoes in the Cascades, and may lead to improved understanding and future projections concerning the timing, frequency and intensity of rain-induced periglacial debris flow events.

Automatic Classification of volcano-seismic events based on Deep Neural Networks.

NASA Astrophysics Data System (ADS)

Titos Luzón, M.; Bueno Rodriguez, A.; Garcia Martinez, L.; Benitez, C.; Ibáñez, J. M.

2017-12-01

Seismic monitoring of active volcanoes is a popular remote sensing technique to detect seismic activity, often associated to energy exchanges between the volcano and the environment. As a result, seismographs register a wide range of volcano-seismic signals that reflect the nature and underlying physics of volcanic processes. Machine learning and signal processing techniques provide an appropriate framework to analyze such data. In this research, we propose a new classification framework for seismic events based on deep neural networks. Deep neural networks are composed by multiple processing layers, and can discover intrinsic patterns from the data itself. Internal parameters can be initialized using a greedy unsupervised pre-training stage, leading to an efficient training of fully connected architectures. We aim to determine the robustness of these architectures as classifiers of seven different types of seismic events recorded at "Volcán de Fuego" (Colima, Mexico). Two deep neural networks with different pre-training strategies are studied: stacked denoising autoencoder and deep belief networks. Results are compared to existing machine learning algorithms (SVM, Random Forest, Multilayer Perceptron). We used 5 LPC coefficients over three non-overlapping segments as training features in order to characterize temporal evolution, avoid redundancy and encode the signal, regardless of its duration. Experimental results show that deep architectures can classify seismic events with higher accuracy than classical algorithms, attaining up to 92% recognition accuracy. Pre-training initialization helps these models to detect events that occur simultaneously in time (such explosions and rockfalls), increase robustness against noisy inputs, and provide better generalization. These results demonstrate deep neural networks are robust classifiers, and can be deployed in real-environments to monitor the seismicity of restless volcanoes.

Characterization of susceptible chiasma configurations that increase the risk for maternal nondisjunction of chromosome 21.

PubMed

Lamb, N E; Feingold, E; Savage, A; Avramopoulos, D; Freeman, S; Gu, Y; Hallberg, A; Hersey, J; Karadima, G; Pettay, D; Saker, D; Shen, J; Taft, L; Mikkelsen, M; Petersen, M B; Hassold, T; Sherman, S L

1997-09-01

Recent studies of trisomy 21 have shown that altered levels of recombination are associated with maternal non-disjunction occurring at both meiosis I (MI) and meiosis II (MII). To comprehend better the association of recombination with nondisjunction, an understanding of the pattern of meiotic exchange, i.e. the exchange of genetic material at the four-strand stage during prophase, is required. We examined this underlying exchange pattern to determine if specific meiotic configurations are associated with a higher risk of non-disjunction than others. We examined the crossover frequencies of chromosome 21 for three populations: (i) normal female meiotic events; (ii) meiotic events leading to MI non-disjunction; and (iii) those leading to MII non-disjunction. From these crossover frequencies, we estimated the array of meiotic tetrads that produced the observed crossovers. Using this approach, we found that nearly one-half of MI errors were estimated to be achiasmate. The majority of the remaining MI bivalents had exchanges that clustered at the telomere. In contrast, exchanges occurring among MII cases clustered at the pericentromeric region of the chromosome. Unlike the single exchange distributions, double exchanges from the non-disjoined populations seemed to approximate the distribution in the normal population. These data suggest that the location of certain exchanges makes a tetrad susceptible to non-disjunction. Specifically, this susceptibility is associated with the distance between the centromere and closest exchange. This result challenges the widely held concept that events occurring at MII are largely independent of events occurring at MI, and suggests that all non-disjunction events may be initiated during MI and simply resolved at either of the two meiotic stages.

The ocean-atmosphere response to wind-induced thermocline changes in the tropical South Western Indian Ocean

NASA Astrophysics Data System (ADS)

Manola, Iris; Selten, F. M.; de Ruijter, W. P. M.; Hazeleger, W.

2015-08-01

In the Indian Ocean basin the sea surface temperatures (SSTs) are most sensitive to changes in the oceanic depth of the thermocline in the region of the Seychelles Dome. Observational studies have suggested that the strong SST variations in this region influence the atmospheric evolution around the basin, while its impact could extend far into the Pacific and the extra-tropics. Here we study the adjustments of the coupled atmosphere-ocean system to a winter shallow doming event using dedicated ensemble simulations with the state-of-the-art EC-Earth climate model. The doming creates an equatorial Kelvin wave and a pair of westward moving Rossby waves, leading to higher SST 1-2 months later in the Western equatorial Indian Ocean. Atmospheric convection is strengthened and the Walker circulation responds with reduced convection over Indonesia and cooling of the SST in that region. The Pacific warm pool convection shifts eastward and an oceanic Kelvin wave is triggered at thermocline depth. The wave leads to an SST warming in the East Equatorial Pacific 5-6 months after the initiation of the Seychelles Dome event. The atmosphere responds to this warming with weak anomalous atmospheric convection. The changes in the upper tropospheric divergence in this sequence of events create large-scale Rossby waves that propagate away from the tropics along the atmospheric waveguides. We suggest to repeat these types of experiments with other models to test the robustness of the results. We also suggest to create the doming event in June so that the East-Pacific warming occurs in November when the atmosphere is most sensitive to SST anomalies and El Niño could possibly be triggered by the doming event under suitable conditions.

Developing an event stratigraphy for Heinrich Event 4 at Eirik Drift, South of Greenland

NASA Astrophysics Data System (ADS)

Stanford, Jennifer; Abbott, Peter; Davies, Siwan

2014-05-01

Heinrich events are characterised in North Atlantic sediments by horizons with increased Ice Rafted Debris (IRD) concentrations, low foraminiferal abundances, and light planktonic foraminiferal calcite δ18O (meltwater dilution). They occurred quasi-periodically with a spacing of 5,000-14,000 yrs (Hemming, 2004). It is commonly believed that large iceberg/meltwater injections likely caused slowdowns of the Atlantic Meridional Overturning Circulation (AMOC). However, Stanford et al. (2011) showed, using a basin-wide reconstruction of Heinrich Event 1 (~19-15 ka BP), which was based upon marine and terrestrial records on carefully scrutinised age models, that the main iceberg discharge event occurred some ~1000 years after the initial AMOC slowdown. The study highlighted the importance of robust chronological constraints in order to permit the development of a process understanding of the evolution of such climate events, by evaluation of statistical uncertainty and robust quantification of leads and lags in the ocean-climate system. Here, we present initial results from a marine sediment core recovered from Eirik Drift, South of Greenland, that span the time period that encompasses Heinrich Event 4 (35-45 ka BP). Today, sediments on Eirik Drift are deposited and reworked by the Deep Western Boundary Current (DWBC) and are also located beneath the pathway of the East Greenland and East Greenland Coastal Currents. Hence, Eirik Drift is a crucial monitoring site of surface and deep waters that exit the Arctic via the Denmark Strait. We here combine a proxy record for North Atlantic Deep Water (NADW) flow intensity (κARM/κ) with co-registered records of surface water conditions and place these on a palaeomagnetic and tephrochronologic stratigraphic framework. Given that this chronological framework is independent of environmental influences, basin-wide signal comparison is therefore permissible. Hemming, S. R. (2004), Heinrich Events: Massive Late Pleistocene detritus layers of the North Atlantic and their global imprint, Rev. Geophys., 42, 1-43. J.D. Stanford, Rohling, E. J., Bacon, S., Roberts, A. P, Grousset, F. E. & Bolshaw, M. (2011), A new concept for the paleoceanographic evolution of Heinrich event 1 in the North Atlantic, Quaternary Science Reviews, 20, 1047-1066

Evaluating average and atypical response in radiation effects simulations

NASA Astrophysics Data System (ADS)

Weller, R. A.; Sternberg, A. L.; Massengill, L. W.; Schrimpf, R. D.; Fleetwood, D. M.

2003-12-01

We examine the limits of performing single-event simulations using pre-averaged radiation events. Geant4 simulations show the necessity, for future devices, to supplement current methods with ensemble averaging of device-level responses to physically realistic radiation events. Initial Monte Carlo simulations have generated a significant number of extremal events in local energy deposition. These simulations strongly suggest that proton strikes of sufficient energy, even those that initiate purely electronic interactions, can initiate device response capable in principle of producing single event upset or microdose damage in highly scaled devices.

Effects of Context on Eye Movements When Reading About Possible and Impossible Events

PubMed Central

Warren, Tessa; McConnell, Kerry; Rayner, Keith

2009-01-01

Plausibility violations resulting in impossible scenarios lead to earlier and longer lasting eye movement disruption than violations resulting in highly unlikely scenarios (K. Rayner, T. Warren, B. J. Juhasz, & S. P. Liversedge, 2004; T. Warren & K. McConnell, 2007). This could reflect either differences in the timing of availability of different kinds of information (e.g., selectional restrictions, world knowledge, and context) or differences in their relative power to guide semantic interpretation. The authors investigated eye movements to possible and impossible events in real-world and fantasy contexts to determine when contextual information influences detection of impossibility cued by a semantic mismatch between a verb and an argument. Gaze durations on a target word were longer to impossible events independent of context. However, a measure of the time elapsed from first fixating the target word to moving past it showed disruption only in the real-world context. These results suggest that contextual information did not eliminate initial disruption but moderated it quickly thereafter. PMID:18605885

The Slope of Change: An Environmental Management Approach to Reduce Drinking on a Day of Celebration at a U.S. College

PubMed Central

Marchell, Timothy C.; Lewis, Deborah D.; Croom, Katherine; Lesser, Martin L.; Murphy, Susan H.; Reyna, Valerie F.; Frank, Jeremy; Staiano-Coico, Lisa

2013-01-01

OBJECTIVE This research extends the literature on event-specific environmental management with a case study evaluation of an intervention designed to reduce student drinking at a university's year-end celebration. PARTICIPANTS Cornell University undergraduates were surveyed each May from 2001 through 2009. Sample sizes ranged from 322 to 1,973. METHODS Randomly sampled surveys were conducted after a large, annual spring campus celebration. An environmental management plan was initiated in 2003 that included increased enforcement of the minimum age drinking law (MADL). RESULTS In the short-term, drinking at the campus celebration decreased while drinking before the event increased. Over time, the intervention significantly reduced high-risk drinking on the day of the event, especially among those under the age of 21. CONCLUSION These findings are contrary to the argument that enforcement of MADLs simply lead to increased high-risk drinking, and therefore have implications for how colleges approach the challenge of student alcohol misuse. PMID:23930747

Irreversible Markov chains in spin models: Topological excitations

NASA Astrophysics Data System (ADS)

Lei, Ze; Krauth, Werner

2018-01-01

We analyze the convergence of the irreversible event-chain Monte Carlo algorithm for continuous spin models in the presence of topological excitations. In the two-dimensional XY model, we show that the local nature of the Markov-chain dynamics leads to slow decay of vortex-antivortex correlations while spin waves decorrelate very quickly. Using a Fréchet description of the maximum vortex-antivortex distance, we quantify the contributions of topological excitations to the equilibrium correlations, and show that they vary from a dynamical critical exponent z∼ 2 at the critical temperature to z∼ 0 in the limit of zero temperature. We confirm the event-chain algorithm's fast relaxation (corresponding to z = 0) of spin waves in the harmonic approximation to the XY model. Mixing times (describing the approach towards equilibrium from the least favorable initial state) however remain much larger than equilibrium correlation times at low temperatures. We also describe the respective influence of topological monopole-antimonopole excitations and of spin waves on the event-chain dynamics in the three-dimensional Heisenberg model.

Lead-Lag relationships? Asynchrounous and Abrupt Shifts in Atmospheric Circulation, Temperature, and Vegetation during the 8.2 ka Event in the Eastern Mediterranean at Tenaghi Philippon, Greece

NASA Astrophysics Data System (ADS)

Niedermeyer, E. M.; Mulch, A.; Pross, J.

2017-12-01

The "8.2 ka event" has been an abrupt and prominent climate perturbation during the Holocene, and is characterized by an episode of generally colder and dryer conditions in the Northern Hemisphere realm. However, evidence to what extent this event has had an impact on climate in the Mediterranean region is ambiguous, in particular with respect to rainfall, temperature and vegetation change on land. Here we present a new, high-resolution record (ø 15 years during the event) of paleotemperatures from the Tenaghi Philippon peat deposit, Eastern Macedonia, Greece, using the MBT'/CBT index based on brGDGTs (branched Glycerol-Dialkyl-Glycerol-Tetraethers). Our data show fairly stable temperatures before the event, which is initiated at 8.1 ka by an abrupt and continuous cooling during the first 35 years of the event. After a short, 10-year episode of minimum temperatures, the event is ended by a similarly abrupt and continuous warming within 38 years. Comparison of our record with a previous study of the stable hydrogen isotopic composition of higher-plant waxes (δDwax) on the same core1 shows that changes in temperature occurred simultaneously with shifts in atmospherics moisture sources (Mediterranean vs Atlantic). Interestingly, further comparison of our data with a previous palynological study of the same core2 reveals that changes in vegetation associated with the 8.2 ka event precede shifts in hydrology and temperature by 100 years. This suggests either pronounced changes in seasonality of temperature and rainfall after the onset of the 8.2 ka event, i.e. at the peak of the event, or that changes in local atmospheric circulation (moisture sources) and temperature where not the initial trigger of changes in vegetation. References: Pross, J., Kotthoff, U., Müller, U.C., Peyron, O., Dormoy, I., Schmiedl, G., Kalaitzidis, S. and Smith, A.M. (2009): Massive perturbation in terrestrial ecosystems of the Eastern Mediterranean region associated with the 8.2 kyr B.P. climatic event. Geology 37, 887-890. Schemmel, F., Niedermeyer, E.M., Schwab, V.F., Gleixner, G., Pross, J. and Mulch, A. (2016): Plant wax δD values record changing Eastern Mediterranean atmospheric circulation patterns during the 8.2 kyr B.P. climatic event. Quaternary Science Reviews 133, 96-107.

Landquake dynamics inferred from seismic source inversion: Greenland and Sichuan events of 2017

NASA Astrophysics Data System (ADS)

Chao, W. A.

2017-12-01

In June 2017 two catastrophic landquake events occurred in Greenland and Sichuan. The Greenland event leads to tsunami hazard in the small town of Nuugaarsiaq. A landquake in Sichuan hit the town, which resulted in over 100 death. Both two events generated the strong seismic signals recorded by the real-time global seismic network. I adopt an inversion algorithm to derive the landquake force time history (LFH) using the long-period waveforms, and the landslide volume ( 76 million m3) can be rapidly estimated, facilitating the tsunami-wave modeling for early warning purpose. Based on an integrated approach involving tsunami forward simulation and seismic waveform inversion, this study has significant implications to issuing actionable warnings before hazardous tsunami waves strike populated areas. Two single-forces (SFs) mechanism (two block model) yields the best explanation for Sichuan event, which demonstrates that secondary event (seismic inferred volume: 8.2 million m3) may be mobilized by collapse-mass hitting from initial rock avalanches ( 5.8 million m3), likely causing a catastrophic disaster. The later source with a force magnitude of 0.9967×1011 N occurred 70 seconds after first mass-movement occurrence. In contrast, first event has the smaller force magnitude of 0.8116×1011 N. In conclusion, seismically inferred physical parameters will substantially contribute to improving our understanding of landquake source mechanisms and mitigating similar hazards in other parts of the world.

Matrix Metalloproteinase Stromelysin-1 Triggers a Cascade of Molecular Alterations that leads to stable epithelial-to-Mesenchymal Conversion and a Premalignant Phenotype in Mammary Epithelial Cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lochter, A.; Galosy, S.; Muschler, J.

1997-08-11

Matrix metalloproteinases (MMPs) regulate ductal morphogenesis, apoptosis, and neoplastic progression in mammary epithelial cells. To elucidate the direct effects of MMPs on mammary epithelium, we generated functionally normal cells expressing an inducible autoactivating stromelysin-1 (SL-1) transgene. Induction of SL-1 expression resulted in cleavage of E-cadherin, and triggered progressive phenotypic conversion characterized by disappearance of E-cadherin and catenins from cell-cell contacts, downregulation of cytokeratins, upregulation of vimentin, induction of keratinocyte growth factor expression and activation, and upregulation of endogenous MMPs. Cells expressing SL-1 were unable to undergo lactogenic differentiation and became invasive. Once initiated, this phenotypic conversion was essentially stable, andmore » progressed even in the absence of continued SL-1 expression. These observations demonstrate that inappropriate expression of SL-1 initiates a cascade of events that may represent a coordinated program leading to loss of the differentiated epithelial phenotype and gain of some characteristics of tumor cells. Our data provide novel insights into how MMPs function in development and neoplastic conversion.« less

Impact of the quasi-biennial oscillation on predictability of the Madden-Julian oscillation

NASA Astrophysics Data System (ADS)

Marshall, Andrew G.; Hendon, Harry H.; Son, Seok-Woo; Lim, Yuna

2017-08-01

The Madden-Julian oscillation (MJO) during boreal winter is observed to be stronger during the easterly phase of the quasi-biennial oscillation (QBO) than during the westerly phase, with the QBO zonal wind at 50 hPa leading enhanced MJO activity by about 1 month. Using 30 years of retrospective forecasts from the POAMA coupled model forecast system, we show that this strengthened MJO activity during the easterly QBO phase translates to improved prediction of the MJO and its convective anomalies across the tropical Indo-Pacific region by about 8 days lead time relative to that during westerly QBO phases. These improvements in forecast skill result not just from the fact that forecasts initialized with stronger MJO events, such as occurs during QBO easterly phases, have greater skill, but also from the more persistent behaviour of the MJO for a similar initial amplitude during QBO easterly phases as compared to QBO westerly phases. The QBO is thus an untapped source of subseasonal predictability that can provide a window of opportunity for improved prediction of global climate.

Plasma membrane signaling in HIV-1 infection.

PubMed

Abbas, Wasim; Herbein, Georges

2014-04-01

Plasma membrane is a multifunctional structure that acts as the initial barrier against infection by intracellular pathogens. The productive HIV-1 infection depends upon the initial interaction of virus and host plasma membrane. Immune cells such as CD4+ T cells and macrophages contain essential cell surface receptors and molecules such as CD4, CXCR4, CCR5 and lipid raft components that facilitate HIV-1 entry. From plasma membrane HIV-1 activates signaling pathways that prepare the grounds for viral replication. Through viral proteins HIV-1 hijacks host plasma membrane receptors such as Fas, TNFRs and DR4/DR5, which results in immune evasion and apoptosis both in infected and uninfected bystander cells. These events are hallmark in HIV-1 pathogenesis that leads towards AIDS. The interplay between HIV-1 and plasma membrane signaling has much to offer in terms of viral fitness and pathogenicity, and a better understanding of this interplay may lead to development of new therapeutic approaches. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking. Copyright © 2013 Elsevier B.V. All rights reserved.

The antidepressant sertraline inhibits translation initiation by curtailing mammalian target of rapamycin signaling.

PubMed

Lin, Chen-Ju; Robert, Francis; Sukarieh, Rami; Michnick, Stephen; Pelletier, Jerry

2010-04-15

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2alpha phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Emu-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. (c) 2010 AACR.

Next Generation Wiring

NASA Technical Reports Server (NTRS)

Medelius, Petro; Jolley, Scott; Fitzpatrick, Lilliana; Vinje, Rubiela; Williams, Martha; Clayton, LaNetra; Roberson, Luke; Smith, Trent; Santiago-Maldonado, Edgardo

2007-01-01

Wiring is a major operational component on aerospace hardware that accounts for substantial weight and volumetric space. Over time wire insulation can age and fail, often leading to catastrophic events such as system failure or fire. The next generation of wiring must be reliable and sustainable over long periods of time. These features will be achieved by the development of a wire insulation capable of autonomous self-healing that mitigates failure before it reaches a catastrophic level. In order to develop a self-healing insulation material, three steps must occur. First, methods of bonding similar materials must be developed that are capable of being initiated autonomously. This process will lead to the development of a manual repair system for polyimide wire insulation. Second, ways to initiate these bonding methods that lead to materials that are similar to the primary insulation must be developed. Finally, steps one and two must be integrated to produce a material that has no residues from the process that degrades the insulating properties of the final repaired insulation. The self-healing technology, teamed with the ability to identify and locate damage, will greatly improve reliability and safety of electrical wiring of critical systems. This paper will address these topics, discuss the results of preliminary testing, and remaining development issues related to self-healing wire insulation.

Suppressed translation as a mechanism of initiation of CASP8 (caspase 8)-dependent apoptosis in autophagy-deficient NSCLC cells under nutrient limitation.

PubMed

Allavena, Giulia; Cuomo, Francesca; Baumgartner, Georg; Bele, Tadeja; Sellgren, Alexander Yarar; Oo, Kyaw Soe; Johnson, Kaylee; Gogvadze, Vladimir; Zhivotovsky, Boris; Kaminskyy, Vitaliy O

2018-01-01

Macroautophagy/autophagy inhibition under stress conditions is often associated with increased cell death. We found that under nutrient limitation, activation of CASP8/caspase-8 was significantly increased in autophagy-deficient lung cancer cells, which precedes mitochondria outer membrane permeabilization (MOMP), CYCS/cytochrome c release, and activation of CASP9/caspase-9, indicating that under such conditions the activation of CASP8 is a primary event in the initiation of apoptosis as well as essential to reduce clonogenic survival of autophagy-deficient cells. Starvation leads to suppression of CFLAR proteosynthesis and accumulation of CASP8 in SQSTM1 puncta. Overexpression of CFLARs reduces CASP8 activation and apoptosis during starvation, while its silencing promotes efficient activation of CASP8 and apoptosis in autophagy-deficient U1810 lung cancer cells even under nutrient-rich conditions. Similar to starvation, inhibition of protein translation leads to efficient activation of CASP8 and cell death in autophagy-deficient lung cancer cells. Thus, here for the first time we report that suppressed translation leads to activation of CASP8-dependent apoptosis in autophagy-deficient NSCLC cells under conditions of nutrient limitation. Our data suggest that targeting translational machinery can be beneficial for elimination of autophagy-deficient cells via the CASP8-dependent apoptotic pathway.

Requirement for the Murine Zinc Finger Protein ZFR in Perigastrulation Growth and Survival

PubMed Central

Meagher, Madeleine J.; Braun, Robert E.

2001-01-01

The transition from preimplantation to postimplantation development leads to the initiation of complex cellular differentiation and morphogenetic movements, a dramatic decrease in cell cycle length, and a commensurate increase in the size of the embryo. Accompanying these changes is the need for the transfer of nutrients from the mother to the embryo and the elaboration of sophisticated genetic networks that monitor genomic integrity and the homeostatic control of cellular growth, differentiation, and programmed cell death. To determine the function of the murine zinc finger protein ZFR in these events, we generated mice carrying a null mutation in the gene encoding it. Homozygous mutant embryos form normal-appearing blastocysts that implant and initiate the process of gastrulation. Mutant embryos form mesoderm but they are delayed in their development and fail to form normal anterior embryonic structures. Loss of ZFR function leads to both an increase in programmed cell death and a decrease in mitotic index, especially in the region of the distal tip of the embryonic ectoderm. Mutant embryos also have an apparent reduction in apical vacuoles in the columnar visceral endoderm cells in the extraembryonic region. Together, these cellular phenotypes lead to a dramatic development delay and embryonic death by 8 to 9 days of gestation, which are independent of p53 function. PMID:11283266

The time course of syntactic activation during language processing: a model based on neuropsychological and neurophysiological data.

PubMed

Friederici, A D

1995-09-01

This paper presents a model describing the temporal and neurotopological structure of syntactic processes during comprehension. It postulates three distinct phases of language comprehension, two of which are primarily syntactic in nature. During the first phase the parser assigns the initial syntactic structure on the basis of word category information. These early structural processes are assumed to be subserved by the anterior parts of the left hemisphere, as event-related brain potentials show this area to be maximally activated when phrase structure violations are processed and as circumscribed lesions in this area lead to an impairment of the on-line structural assignment. During the second phase lexical-semantic and verb-argument structure information is processed. This phase is neurophysiologically manifest in a negative component in the event-related brain potential around 400 ms after stimulus onset which is distributed over the left and right temporo-parietal areas when lexical-semantic information is processed and over left anterior areas when verb-argument structure information is processed. During the third phase the parser tries to map the initial syntactic structure onto the available lexical-semantic and verb-argument structure information. In case of an unsuccessful match between the two types of information reanalyses may become necessary. These processes of structural reanalysis are correlated with a centroparietally distributed late positive component in the event-related brain potential.(ABSTRACT TRUNCATED AT 250 WORDS)

Cavitation-induced fragmentation of an acoustically-levitated droplet

NASA Astrophysics Data System (ADS)

Gonzalez Avila, Silvestre Roberto; Ohl, Claus-Dieter

2015-12-01

In this paper we investigate the initial sequence of events that lead to the fragmentation of a millimetre sized water droplets when interacting with a focused ns-laser pulse. The experimental results show complex processes that result from the reflection of an initial shock wave from plasma generation with the soft boundary of the levitating droplet; furthermore, when the reflected waves from the walls of the droplet refocus they leave behind a trail of microbubbles that later act as cavitation inception regions. Numerical simulations of a shock wave impacting and reflecting from a soft boundary are also reported; the simulated results show that the lowest pressure inside the droplet occurs at the equatorial plane. The results of the numerical model display good agreement with the experimental results both in time and in space.

Th2 and Th1 Responses: Clear and Hidden Sides of Immunity Against Intestinal Helminths.

PubMed

Cortés, Alba; Muñoz-Antoli, Carla; Esteban, J Guillermo; Toledo, Rafael

2017-09-01

Intestinal helminthiases affect millions of people worldwide, mainly in developing regions, where they cause a significant negative impact on human health and socioeconomic growth of affected populations. However, intestinal helminthiases are still among the most neglected tropical diseases. Protective immunity against intestinal helminths is associated with development of type 2 responses. Nevertheless, in some host-intestinal helminth combinations, local Th1 responses are initiated, inducing chronicity. The usage of helminth-mouse models is useful for elucidating the mechanisms behind the initiation of each type of response. Herein, the current knowledge on these topics is reviewed, paying particular attention to the earliest events of the immune cascade which eventually lead to either susceptibility or resistance to infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Tobacco Advertising and Promotional Expenditures in Sports and Sporting Events - United States, 1992-2013.

PubMed

Agaku, Israel T; Odani, Satomi; Sturgis, Stephanie; Harless, Charles; Glover-Kudon, Rebecca

2016-08-19

Smokeless tobacco has been actively promoted by tobacco companies using endorsements by major sport figures, and research indicates that tobacco advertising can lead to youth initiation of tobacco use (1,2). Television and radio advertisements for cigarettes and smokeless tobacco have been prohibited since 1969,* and the 1998 Master Settlement Agreement(†) further prohibited tobacco companies from targeting youths with tobacco product advertisements in specified areas. In 2010, the Food and Drug Administration (FDA), under authority of the 2009 Family Smoking Prevention and Tobacco Control Act (FSPTCA), prohibited tobacco-brand sponsorship (i.e., sponsorship of sports and entertainment events or other social or cultural events using the tobacco brand name or anything identifiable with any brand of cigarettes or smokeless tobacco).(§) However, corporate-name tobacco sponsorship (i.e., sponsorship using the name of the corporation that manufactures regulated tobacco products) is still permitted under certain conditions.(¶) To monitor tobacco advertising and promotional activities in sports in the United States, CDC analyzed trends in sports-related marketing expenditures for cigarettes and smokeless tobacco during 1992-2013 using data from the Federal Trade Commission (FTC). During 1992-2013, sports-related marketing expenditures, adjusted by the consumer price index to constant 2013 dollars, decreased significantly for both cigarettes (from $136 million in 1992 to $0 in 2013) and smokeless tobacco (from $34.8 million in 1992 to $2.1 million in 2013). During 2010-2013, after the prohibition of tobacco-brand sponsorship in sports under the FSPTCA, cigarette manufacturers reported no spending (i.e., $0) on sports-related advertising and promotional activities; in contrast, smokeless tobacco manufacturers reported expenditures of $16.3 million on advertising and promoting smokeless tobacco in sports during 2010-2013. These findings indicate that despite prohibitions on brand sponsorship, smokeless tobacco products continue to be marketed in sports in the United States, potentially through other indirect channels such as corporate-name sponsorship. Enhanced measures are warranted to restrict youth-oriented tobacco marketing and promotional activities that could lead to tobacco initiation and use among children and adolescents (2). Reducing tobacco industry promotion through sponsorship of public and private events is an evidence-based strategy for preventing youth initiation of tobacco use (3). In addition, other proven interventions (e.g., tobacco price increases, anti-tobacco mass media campaigns, tobacco-free policies inclusive of smokeless tobacco, and barrier-free access to cessation services), could help reduce smokeless tobacco use in the United States (1).

Monoamines stimulate sex reversal in the saddleback wrasse.

PubMed

Larson, Earl T; Norris, David O; Gordon Grau, E; Summers, Cliff H

2003-02-15

Monoamine neurotransmitters (norepinephrine, dopamine, and serotonin) play an important role in reproduction and sexual behavior throughout the vertebrates. They are the first endogenous chemical signals in the regulation of the hypothalamo-pituitary-gonadal (HPG) axis. In teleosts with behavioral sex determination, much is known about behavioral cues that induce sex reversal. The cues are social, processed via the visual system and depend on the ratio of females to males in the population. The mechanisms by which these external behavioral cues are converted to an internal chemical regulatory process are largely unknown. The protogynous Hawaiian saddleback wrasse, Thalassoma duperrey, was used to investigate the biological pathway mediating the conversion of a social cue into neuroendocrine events regulating sex reversal. Because monoamines play an important role in the regulation of the HPG axis, they were selected as likely candidates for such a conversion. To determine if monoamines could affect sex reversal, drugs affecting monoamines were used in an attempt to either induce sex reversal under non-permissive conditions, or prevent sex reversal under permissive conditions. Increasing norepinephrine or blocking dopamine or serotonin lead to sex reversal in experimental animals under non-permissive conditions. Increasing serotonin blocked sex reversal under permissive conditions, while blocking dopamine or norepinephrine retarded the process. The results presented here demonstrate that monoamines contribute significantly to the control sex reversal. Norepinephrine stimulates initiation and completion of gonadal sex of reversal as well as color change perhaps directly via its effects on the HPG axis. Dopamine exercises inhibitory action on the initiation of sex reversal while 5-HT inhibits both initiation and completion of sex reversal. The serotonergic system appears to be an integral part of the pathway mediating the conversion of a social cue into a neuroendocrine event. The complex organization of neurochemical events controlling the psychosocial, physiological, and anatomical events that constitute reversal of sexual identity includes monoamine neurotransmitters. Copyright 2003 Elsevier Science (USA)

The Role of Climatic Conditions in Controlling Observed Variability of Timing and Peak Discharge of Glacial Lake Outburst Floods: Lago Cachet Dos, Chile

NASA Astrophysics Data System (ADS)

Jacquet, J.; McCoy, S. W.; McGrath, D.; Nimick, D.; Friesen, B.; Fahey, M. J.; Leidich, J.; Okuinghttons, J.

2016-12-01

The sudden release of water from an ice-dammed lake poses substantial hazard to the downstream environment, but predicting the timing and magnitude of such an event is difficult. We use a series of high-resolution discharge measurements from a glacier-dammed lake, Lago Cachet Dos (LC2), during outburst events to evaluate the environmental conditions that influence the timing of initiation and peak discharge of observed glacial lake outburst floods (GLOFs). Since April 2008, 20 GLOFs have initiated out of LC2, located on the eastern edge of the Northern Patagonia Icefield, Chile and flooded areas along the Rio Colonia- Rio Baker system. GLOF frequency has averaged 2-3 events annually and peak discharges exiting LC2 have ranged widely from 2,000 to >15,000 m3 s-1. Although some LC2 GLOFs are consistent with global compilations relating peak discharge to lake volume, large deviations from the global trend and large intra-event variability are striking and call into question the predictive ability of simple empirical scaling equations. To evaluate the environmental conditions that lead to variability in observed peak discharge, we use a variation of the theoretical model of Nye (1976), which describes the process of englacial conduit evolution as a competition between thermally induced conduit growth and viscous flow of ice causing conduit collapse. We show that, consistent with theory, initial lake volume, lake temperature, and the rate of meltwater input into the glacially dammed lake all influence the peak discharge of measured GLOFs. Consequently, evolving climatic conditions of a region can greatly influence the potential hazard of GLOFs. Our results suggest that more accurate predictions of GLOF timing and magnitude from ice dammed lakes can be made by incorporating additional measurements of environmental conditions.

A fuzzy Petri-net-based mode identification algorithm for fault diagnosis of complex systems

NASA Astrophysics Data System (ADS)

Propes, Nicholas C.; Vachtsevanos, George

2003-08-01

Complex dynamical systems such as aircraft, manufacturing systems, chillers, motor vehicles, submarines, etc. exhibit continuous and event-driven dynamics. These systems undergo several discrete operating modes from startup to shutdown. For example, a certain shipboard system may be operating at half load or full load or may be at start-up or shutdown. Of particular interest are extreme or "shock" operating conditions, which tend to severely impact fault diagnosis or the progression of a fault leading to a failure. Fault conditions are strongly dependent on the operating mode. Therefore, it is essential that in any diagnostic/prognostic architecture, the operating mode be identified as accurately as possible so that such functions as feature extraction, diagnostics, prognostics, etc. can be correlated with the predominant operating conditions. This paper introduces a mode identification methodology that incorporates both time- and event-driven information about the process. A fuzzy Petri net is used to represent the possible successive mode transitions and to detect events from processed sensor signals signifying a mode change. The operating mode is initialized and verified by analysis of the time-driven dynamics through a fuzzy logic classifier. An evidence combiner module is used to combine the results from both the fuzzy Petri net and the fuzzy logic classifier to determine the mode. Unlike most event-driven mode identifiers, this architecture will provide automatic mode initialization through the fuzzy logic classifier and robustness through the combining of evidence of the two algorithms. The mode identification methodology is applied to an AC Plant typically found as a component of a shipboard system.

The Influence of Aerosol Hygroscopicity on Precipitation Intensity During a Mesoscale Convective Event

NASA Astrophysics Data System (ADS)

Kawecki, Stacey; Steiner, Allison L.

2018-01-01

We examine how aerosol composition affects precipitation intensity using the Weather and Research Forecasting Model with Chemistry (version 3.6). By changing the prescribed default hygroscopicity values to updated values from laboratory studies, we test model assumptions about individual component hygroscopicity values of ammonium, sulfate, nitrate, and organic species. We compare a baseline simulation (BASE, using default hygroscopicity values) with four sensitivity simulations (SULF, increasing the sulfate hygroscopicity; ORG, decreasing organic hygroscopicity; SWITCH, using a concentration-dependent hygroscopicity value for ammonium; and ALL, including all three changes) to understand the role of aerosol composition on precipitation during a mesoscale convective system (MCS). Overall, the hygroscopicity changes influence the spatial patterns of precipitation and the intensity. Focusing on the maximum precipitation in the model domain downwind of an urban area, we find that changing the individual component hygroscopicities leads to bulk hygroscopicity changes, especially in the ORG simulation. Reducing bulk hygroscopicity (e.g., ORG simulation) initially causes fewer activated drops, weakened updrafts in the midtroposphere, and increased precipitation from larger hydrometeors. Increasing bulk hygroscopicity (e.g., SULF simulation) simulates more numerous and smaller cloud drops and increases precipitation. In the ALL simulation, a stronger cold pool and downdrafts lead to precipitation suppression later in the MCS evolution. In this downwind region, the combined changes in hygroscopicity (ALL) reduces the overprediction of intense events (>70 mm d-1) and better captures the range of moderate intensity (30-60 mm d-1) events. The results of this single MCS analysis suggest that aerosol composition can play an important role in simulating high-intensity precipitation events.

Intermittent blood pressure control: potential consequences for outcome.

PubMed

Leenen, F H

1999-05-01

Although both blood pressure (BP) and left ventricular (LV) mass at initial evaluation predict future cardiovascular risk, the actual BP and LV mass achieved over years of treatment more clearly relate to cardiovascular event rates. Intermittent compliance or noncompliance is the major reason for uncontrolled hypertension and presumably persistent LV hypertrophy. In general, drugs with rapid onset and short duration of action are not desirable because this profile may lead to large variations in BP lowering effect during actual drug intake and rapid disappearance of the antihypertensive effect with missed doses. In addition, intermittent compliance per se introduces the potential for adverse events. For drugs requiring several dose-titrations (e.g., alpha1-blockers), restarting at full doses may lead to excessive drug action and symptomatic hypotension. For other drugs (e.g., short acting beta-blockers or clonidine-like drugs), sudden discontinuation with intermittent compliance may lead to rebound-enhanced sympathetic responsiveness after one to two days, resulting not only in side effects, but also in adverse events, particularly in patients with (silent) coronary artery disease. The rapid onset, short acting dihydropyridines cause intermittent BP control at each dosing, particularly at higher doses. This intermittent control of BP is even more apparent at dosing intervals that are long relative to the duration of action. Thus, sympathetic activation and potential for adverse events can be anticipated at each dosing unless these drugs are being taken frequently at relatively low doses. For diuretics, angiotensin-converting enzyme inhibitors and angiotensin I receptor blockers, no adverse effects have been identified with intermittent compliance. Intermittent BP control is, in general, not an appropriate approach to the management of hypertension and introduces additional risks depending on the type of antihypertensive drug. In contrast, drugs with slow onset and long duration of action provide a more consistent effect during actual drug intake and a more persistent effect during short periods of noncompliance.

Reconstruction of flood events based on documentary data and transnational flood risk analysis of the Upper Rhine and its French and German tributaries since AD 1480

NASA Astrophysics Data System (ADS)

Himmelsbach, I.; Glaser, R.; Schoenbein, J.; Riemann, D.; Martin, B.

2015-10-01

This paper presents the long-term analysis of flood occurrence along the southern part of the Upper Rhine River system and of 14 of its tributaries in France and Germany covering the period starting from 1480 BC. Special focus is given on the temporal and spatial variations of flood events and their underlying meteorological causes over time. Examples are presented of how long-term information about flood events and knowledge about the historical aspect of flood protection in a given area can help to improve the understanding of risk analysis and therefor transnational risk management. Within this context, special focus is given to flood vulnerability while comparing selected historical and modern extreme events, establishing a common evaluation scheme. The transnational aspect becomes especially evident analyzing the tributaries: on this scale, flood protection developed impressively different on the French and German sides. We argue that comparing high technological standards of flood protection, which were initiated by the dukes of Baden on the German side starting in the early 19th century, misled people to the common belief that the mechanical means of flood protection like dams and barrages can guarantee the security from floods and their impacts. This lead to widespread settlements and the establishment of infrastructure as well as modern industries in potentially unsafe areas until today. The legal status in Alsace on the French side of the Rhine did not allow for continuous flood protection measurements, leading to a constant - and probably at last annoying - reminder that the floodplains are a potentially unsafe place to be. From a modern perspective of flood risk management, this leads to a significant lower aggregation of value in the floodplains of the small rivers in Alsace compared to those on the Baden side - an interesting fact - especially if the modern European Flood directive is taken into account.

WRF model performance under flash-flood associated rainfall

NASA Astrophysics Data System (ADS)

Mejia-Estrada, Iskra; Bates, Paul; Ángel Rico-Ramírez, Miguel

2017-04-01

Understanding the natural processes that precede the occurrence of flash floods is crucial to improve the future flood projections in a changing climate. Using numerical weather prediction tools allows to determine one of the triggering conditions for these particularly dangerous events, difficult to forecast due to their short lead-time. However, simulating the spatial and temporal evolution of the rainfall that leads to a rapid rise in river levels requires determining the best model configuration without compromising the computational efficiency. The current research involves the results of the first part of a cascade modeling approach, where the Weather Research and Forecasting (WRF) model is used to simulate the heavy rainfall in the east of the UK in June 2012 when stationary thunderstorms caused 2-hour accumulated values to match those expected in the whole month of June over the city of Newcastle. The optimum model set-up was obtained after extensive testing regarding physics parameterizations, spin-up times, datasets used as initial conditions and model resolution and nesting, hence determining its sensitivity to reproduce localised events of short duration. The outputs were qualitatively and quantitatively assessed using information from the national weather radar network as well as interpolated rainfall values from gauges, respectively. Statistical and skill score values show that the model is able to produce reliable accumulated precipitation values while explicitly solving the atmospheric equations in high resolution domains as long as several hydrometeors are considered with a spin-up time that allows the model to assimilate the initial conditions without going too far back in time from the event of interest. The results from the WRF model will serve as input to run a semi-distributed hydrological model to determine the rainfall-runoff relationship within an uncertainty assessment framework that will allow evaluating the implications of assumptions at the top of the modeling process in the final outputs of the cascade.

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE PAGES

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela; ...

2017-03-15

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

Modeling the influence of string collective phenomena on the long range rapidity correlations between the transverse momentum and the multiplicities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andronov, E.; Vechernin, V.

2016-01-22

The long-range rapidity correlations between the multiplicities (n-n) and the transverse momentum and the multiplicity (pT-n) of charge particles are analyzed in the framework of the simple string inspired model with two types of sources. The sources of the first type correspond to the initial strings formed in a hadronic collision. The sources of the second type imitate the appearance of the emitters of a new kind resulting from interaction (fusion) of the initial strings. The model enabled to describe effectively the influence of the string fusion effects on the strength both the n-n and the pT-n correlations. It wasmore » found that in the region, where the process of string fusion comes into play, the calculation results predict the non-monotonic behaviour of the n-n and pT-n correlation coefficients with the growth of the mean number of initial strings, i.e. with the increase of the collision centrality. It was shown also that the increase of the event-by-event fluctuation in the number of primary strings leads to the change of the pT-n correlation sign from negative to positive. One can try to search these signatures of string collective phenomena in interactions of various nuclei at different energies varying the class of collision centrality and its width.« less

Breath-giving cooperation: critical review of origin of mitochondria hypotheses : Major unanswered questions point to the importance of early ecology.

PubMed

Zachar, István; Szathmáry, Eörs

2017-08-14

The origin of mitochondria is a unique and hard evolutionary problem, embedded within the origin of eukaryotes. The puzzle is challenging due to the egalitarian nature of the transition where lower-level units took over energy metabolism. Contending theories widely disagree on ancestral partners, initial conditions and unfolding of events. There are many open questions but there is no comparative examination of hypotheses. We have specified twelve questions about the observable facts and hidden processes leading to the establishment of the endosymbiont that a valid hypothesis must address. We have objectively compared contending hypotheses under these questions to find the most plausible course of events and to draw insight on missing pieces of the puzzle. Since endosymbiosis borders evolution and ecology, and since a realistic theory has to comply with both domains' constraints, the conclusion is that the most important aspect to clarify is the initial ecological relationship of partners. Metabolic benefits are largely irrelevant at this initial phase, where ecological costs could be more disruptive. There is no single theory capable of answering all questions indicating a severe lack of ecological considerations. A new theory, compliant with recent phylogenomic results, should adhere to these criteria. This article was reviewed by Michael W. Gray, William F. Martin and Purificación López-García.

SeqAPASS: Sequence alignment to predict across-species ...

EPA Pesticide Factsheets

Efforts to shift the toxicity testing paradigm from whole organism studies to those focused on the initiation of toxicity and relevant pathways have led to increased utilization of in vitro and in silico methods. Hence the emergence of high through-put screening (HTS) programs, such as U.S. EPA ToxCast, and application of the adverse outcome pathway (AOP) framework for identifying and defining biological key events triggered upon perturbation of molecular initiating events and leading to adverse outcomes occuring at a level of organization relevant for risk assessment [1]. With these recent initiatives to harness the power of “the pathway” in describing and evaluating toxicity comes the need to extrapolate data beyond the model species. Sequence alignment to predict across-species susceptibilty (SeqAPASS) is a web-based tool that allows the user to begin to understand how broadly HTS data or AOP constructs may plausibly be extrapolated across species, while describing the relative intrinsic susceptibiltiy of different taxa to chemicals with known modes of action (e.g., pharmaceuticals and pesticides). The tool rapidly and strategically assesses available molecular target information to describe protein sequence similarity at the primary amino acid sequence, conserved domain, and individual amino acid residue levels. This in silico approach to species extrapolation was designed to automate and streamline the relatively complex and time-consuming process of co

Surgically induced neuropathic pain: understanding the perioperative process.

PubMed

Borsook, David; Kussman, Barry D; George, Edward; Becerra, Lino R; Burke, Dennis W

2013-03-01

Nerve damage takes place during surgery. As a consequence, significant numbers (10%-40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in "peripheral and central sensitization," with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients, these initial events produce chemical, structural, and functional changes in the peripheral and central nervous systems (CNS). The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state-allodynia, sensory loss, shooting pains, etc, that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed "centralization of pain" and affect sensory, emotional, and other (eg, cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (eg, depression). Currently there are no objective measures of nociception and pain in the perioperative period. As such, intermittent or continuous pain may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition, appear to provide initial opportunities for decreasing the burden of SNPP, until treatments with high efficacy and low adverse effects that either prevent or treat pain are discovered.

Staged induction of HIV-1 glycan–dependent broadly neutralizing antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bonsignori, Mattia; Kreider, Edward F.; Fera, Daniela

A preventive HIV-1 vaccine should induce HIV-1–specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3- glycan bnAb. Two autologousmore » neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3- glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs.« less

An important erosion process on steep burnt hillslopes

NASA Astrophysics Data System (ADS)

Langhans, Christoph; Nyman, Petter; Noske, Philip; Lane, Patrick; Sheridan, Gary

2016-04-01

Steep forested hillslopes often display a high degree of armouring where diffusive erosion processes preferentially remove the fine fraction of the surface soil. High infiltration capacities, hydraulic resistance to overland flow and physical anchoring by cover plants and litter mean that even the most extreme rainfall events usually do not erode the armouring substantially. We argue that fire (wild or planned) is essential to the mobilization and transport of the armouring by increasing the rates of overland flow and decreasing trapping opportunities. We present evidence of the types of erosion that lead to the stripping of the surface armouring using post-event surveys and high-rate overland flow experiments. The type of erosion depends on the relative abundance of non-cohesive surface material to overland flow, but we found that a particular type of transport dominates that has no representation in current erosion models: On steep slopes overland flow can lead to incipient motion of individual stones that transfer their momentum to other stones leading to a rapid mobilization of the whole non-cohesive, armoured surface layer. Once in motion, the layer quickly separates out into a granular flow front and liquefied body, akin to debris flows in channels. Depending on the size of the event, these hillslope debris flows (HDF) either get trapped or enter into the channel, stripping the hillslope of most armouring on their way. They provide channels with the material and shear stress needed to erode into the channel bed, increasing the risk of channel debris flows. We present a simple physical model of HDF initiation, movement, and possible re-mobilization on hillslopes that was derived from debris flow theory. Understanding this process, its frequency, and magnitude are important for assessing the role of fire in landscape evolution and risk to humans through debris flow impacts.

Evaluation of the skill of North-American Multi-Model Ensemble (NMME) Global Climate Models in predicting average and extreme precipitation and temperature over the continental USA

NASA Astrophysics Data System (ADS)

Slater, Louise J.; Villarini, Gabriele; Bradley, Allen A.

2016-08-01

This paper examines the forecasting skill of eight Global Climate Models from the North-American Multi-Model Ensemble project (CCSM3, CCSM4, CanCM3, CanCM4, GFDL2.1, FLORb01, GEOS5, and CFSv2) over seven major regions of the continental United States. The skill of the monthly forecasts is quantified using the mean square error skill score. This score is decomposed to assess the accuracy of the forecast in the absence of biases (potential skill) and in the presence of conditional (slope reliability) and unconditional (standardized mean error) biases. We summarize the forecasting skill of each model according to the initialization month of the forecast and lead time, and test the models' ability to predict extended periods of extreme climate conducive to eight `billion-dollar' historical flood and drought events. Results indicate that the most skillful predictions occur at the shortest lead times and decline rapidly thereafter. Spatially, potential skill varies little, while actual model skill scores exhibit strong spatial and seasonal patterns primarily due to the unconditional biases in the models. The conditional biases vary little by model, lead time, month, or region. Overall, we find that the skill of the ensemble mean is equal to or greater than that of any of the individual models. At the seasonal scale, the drought events are better forecast than the flood events, and are predicted equally well in terms of high temperature and low precipitation. Overall, our findings provide a systematic diagnosis of the strengths and weaknesses of the eight models over a wide range of temporal and spatial scales.

75 FR 38078 - Manufacturing and Services' Manufacture America Initiative and Events

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-01

... DEPARTMENT OF COMMERCE International Trade Administration Manufacturing and Services' Manufacture America Initiative and Events ACTION: Notice of series of regional events and supportive resources to promote growth and retooling in manufacturing. SUMMARY: The International Trade Administration's...

Cell-type-specific replication initiation programs set fragility of the FRA3B fragile site.

PubMed

Letessier, Anne; Millot, Gaël A; Koundrioukoff, Stéphane; Lachagès, Anne-Marie; Vogt, Nicolas; Hansen, R Scott; Malfoy, Bernard; Brison, Olivier; Debatisse, Michelle

2011-02-03

Common fragile sites have long been identified by cytogeneticists as chromosomal regions prone to breakage upon replication stress. They are increasingly recognized to be preferential targets for oncogene-induced DNA damage in pre-neoplastic lesions and hotspots for chromosomal rearrangements in various cancers. Common fragile site instability was attributed to the fact that they contain sequences prone to form secondary structures that may impair replication fork movement, possibly leading to fork collapse resulting in DNA breaks. Here we show, in contrast to this view, that the fragility of FRA3B--the most active common fragile site in human lymphocytes--does not rely on fork slowing or stalling but on a paucity of initiation events. Indeed, in lymphoblastoid cells, but not in fibroblasts, initiation events are excluded from a FRA3B core extending approximately 700 kilobases, which forces forks coming from flanking regions to cover long distances in order to complete replication. We also show that origins of the flanking regions fire in mid-S phase, leaving the site incompletely replicated upon fork slowing. Notably, FRA3B instability is specific to cells showing this particular initiation pattern. The fact that both origin setting and replication timing are highly plastic in mammalian cells explains the tissue specificity of common fragile site instability we observed. Thus, we propose that common fragile sites correspond to the latest initiation-poor regions to complete replication in a given cell type. For historical reasons, common fragile sites have been essentially mapped in lymphocytes. Therefore, common fragile site contribution to chromosomal rearrangements in tumours should be reassessed after mapping fragile sites in the cell type from which each tumour originates.

Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage.

PubMed

Mayer, Wolfgang J; Hakim, Imad; Haritoglou, Christos; Gandorfer, Arnd; Ulbig, Michael; Kampik, Anselm; Wolf, Armin

2013-05-01

To report the 12 months efficacy of initial intravitreal bevacizumab or intravitreal recombinant tissue plasminogen activator (rtPA) combined with expansile gas in patients with subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). Forty-five eyes of 45 patients with subretinal haemorrhage (1-5 disc diameters) involving the fovea secondary to neovascular AMD were evaluated retrospectively consecutively. Thirty-two eyes underwent treatment with rtPA (50 μg/0.05 ml) combined with intravitreal sulphur hexafluoride (SF6). The other 13 eyes were treated with bevacizumab (1.25 mg/0.05 ml) and SF6. Thereafter, all patients received Vascular Endothelial Growth Factor (anti-VEGF) treatment according to modified PrONTO criteria. Main outcome was change of best-corrected visual acuity (VA) at 12 months as determined by Early Treatment Diabetic Retinopathy (ETDRS). There was more improvement in patients initially treated with rtPA and gas (14 letters; bevacizumab and gas eight letters) and not suffering from adverse events. The incidence of vitreous haemorrhages was significantly higher in the rtPA group (nine of 32 versus one of 13, p < 0.01). In both groups, an average of 3.5 anti-VEGF injections were performed per patient during 12 months (no difference between both groups). Both initial treatment regimen lead to improved functional results after 1 year. However, patients, not suffering from adverse events, who underwent initial treatment with rtPA and gas showed better results. To maintain VA, controlling neovascular AMD by anti-VEGF treatment regime after initial treatment with rtPA+gas is important for all cases. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Critical role of canonical transient receptor potential channel 7 in initiation of seizures.

PubMed

Phelan, Kevin D; Shwe, U Thaung; Abramowitz, Joel; Birnbaumer, Lutz; Zheng, Fang

2014-08-05

Status epilepticus (SE) is a life-threatening disease that has been recognized since antiquity but still causes over 50,000 deaths annually in the United States. The prevailing view on the pathophysiology of SE is that it is sustained by a loss of normal inhibitory mechanisms of neuronal activity. However, the early process leading to the initiation of SE is not well understood. Here, we show that, as seen in electroencephalograms, SE induced by the muscarinic agonist pilocarpine in mice is preceded by a specific increase in the gamma wave, and genetic ablation of canonical transient receptor potential channel (TRPC) 7 significantly reduces this pilocarpine-induced increase of gamma wave activity, preventing the occurrence of SE. At the cellular level, TRPC7 plays a critical role in the generation of spontaneous epileptiform burst firing in cornu ammonis (CA) 3 pyramidal neurons in brain slices. At the synaptic level, TRPC7 plays a significant role in the long-term potentiation at the CA3 recurrent collateral synapses and Schaffer collateral-CA1 synapses, but not at the mossy fiber-CA3 synapses. Taken together, our data suggest that epileptiform burst firing generated in the CA3 region by activity-dependent enhancement of recurrent collateral synapses may be an early event in the initiation process of SE and that TRPC7 plays a critical role in this cellular event. Our findings reveal that TRPC7 is intimately involved in the initiation of seizures both in vitro and in vivo. To our knowledge, this contribution to initiation of seizures is the first identified functional role for the TRPC7 ion channel.

Tropical river suspended sediment and solute dynamics in storms during an extreme drought

NASA Astrophysics Data System (ADS)

Clark, Kathryn E.; Shanley, James B.; Scholl, Martha A.; Perdrial, Nicolas; Perdrial, Julia N.; Plante, Alain F.; McDowell, William H.

2017-05-01

Droughts, which can strongly affect both hydrologic and biogeochemical systems, are projected to become more prevalent in the tropics in the future. We assessed the effects of an extreme drought during 2015 on stream water composition in the Luquillo Mountains of Puerto Rico. We demonstrated that drought base flow in the months leading up to the study was sourced from trade-wind orographic rainfall, suggesting a resistance to the effects of an otherwise extreme drought. In two catchments (Mameyes and Icacos), we sampled a series of four rewetting events that partially alleviated the drought. We collected and analyzed dissolved constituents (major cations and anions, organic carbon, and nitrogen) and suspended sediment (inorganic and organic matter (particulate organic carbon and particulate nitrogen)). The rivers appeared to be resistant to extreme drought, recovering quickly upon rewetting, as (1) the concentration-discharge (C-Q) relationships deviated little from the long-term patterns; (2) "new water" dominated streamflow during the latter events; (3) suspended sediment sources had accumulated in the channel during the drought flushed out during the initial events; and (4) the severity of the drought, as measured by the US drought monitor, was reduced dramatically after the rewetting events. Through this interdisciplinary study, we were able to investigate the impact of extreme drought through rewetting events on the river biogeochemistry.

Seismology-based early identification of dam-formation landquake events.

PubMed

Chao, Wei-An; Zhao, Li; Chen, Su-Chin; Wu, Yih-Min; Chen, Chi-Hsuan; Huang, Hsin-Hua

2016-01-12

Flooding resulting from the bursting of dams formed by landquake events such as rock avalanches, landslides and debris flows can lead to serious bank erosion and inundation of populated areas near rivers. Seismic waves can be generated by landquake events which can be described as time-dependent forces (unloading/reloading cycles) acting on the Earth. In this study, we conduct inversions of long-period (LP, period ≥20 s) waveforms for the landquake force histories (LFHs) of ten events, which provide quantitative characterization of the initiation, propagation and termination stages of the slope failures. When the results obtained from LP waveforms are analyzed together with high-frequency (HF, 1-3 Hz) seismic signals, we find a relatively strong late-arriving seismic phase (dubbed Dam-forming phase or D-phase) recorded clearly in the HF waveforms at the closest stations, which potentially marks the time when the collapsed masses sliding into river and perhaps even impacting the topographic barrier on the opposite bank. Consequently, our approach to analyzing the LP and HF waveforms developed in this study has a high potential for identifying five dam-forming landquake events (DFLEs) in near real-time using broadband seismic records, which can provide timely warnings of the impending floods to downstream residents.

Late Lutetian Thermal Maximum—Crossing a Thermal Threshold in Earth's Climate System?

NASA Astrophysics Data System (ADS)

Westerhold, T.; Röhl, U.; Donner, B.; Frederichs, T.; Kordesch, W. E. C.; Bohaty, S. M.; Hodell, D. A.; Laskar, J.; Zeebe, R. E.

2018-01-01

Recognizing and deciphering transient global warming events triggered by massive release of carbon into Earth's ocean-atmosphere climate system in the past are important for understanding climate under elevated pCO2 conditions. Here we present new high-resolution geochemical records including benthic foraminiferal stable isotope data with clear evidence of a short-lived (30 kyr) warming event at 41.52 Ma. The event occurs in the late Lutetian within magnetochron C19r and is characterized by a ˜2°C warming of the deep ocean in the southern South Atlantic. The magnitudes of the carbon and oxygen isotope excursions of the Late Lutetian Thermal Maximum are comparable to the H2 event (53.6 Ma) suggesting a similar response of the climate system to carbon cycle perturbations even in an already relatively cooler climate several million years after the Early Eocene Climate Optimum. Coincidence of the event with exceptionally high insolation values in the Northern Hemisphere at 41.52 Ma might indicate that Earth's climate system has a thermal threshold. When this tipping point is crossed, rapid positive feedback mechanisms potentially trigger transient global warming. The orbital configuration in this case could have caused prolonged warm and dry season leading to a massive release of terrestrial carbon into the ocean-atmosphere system initiating environmental change.

Simulations and experiments of ejecta generation in twice-shocked metals

NASA Astrophysics Data System (ADS)

Karkhanis, Varad; Ramaprabhu, Praveen; Buttler, William; Hammerberg, James; Cherne, Frank; Andrews, Malcolm

2016-11-01

Using continuum hydrodynamics embedded in the FLASH code, we model ejecta generation in recent target experiments, where a metallic surface was loaded by two successive shock waves. The experimental data were obtained from a two-shockwave, high-explosive tool at Los Alamos National Laboratory, capable of generating ejecta from a shocked tin surface in to a vacuum. In both simulations and experiment, linear growth is observed following the first shock event, while the second shock strikes a finite-amplitude interface leading to nonlinear growth. The timing of the second incident shock was varied systematically in our simulations to realize a finite-amplitude re-initialization of the RM instability driving the ejecta. We find the shape of the interface at the event of second shock is critical in determining the amount of ejecta, and thus must be used as an initial condition to evaluate subsequent ejected mass using a source model. In particular, the agreement between simulations, experiments and the mass model is improved when shape effects associated with the interface at second shock are incorporated. This work was supported in part by the (U.S.) Department of Energy (DOE) under Contract No. DE-AC52-06NA2-5396.

Stochastic phase of ventral furrow formation in the Drosophila embryo: cellular constriction chains, mechanical feedback, and robustness

NASA Astrophysics Data System (ADS)

Blawzdziewicz, Jerzy; Gao, Guo-Jie J.; Holcomb, Michael C.; Thomas, Jeffrey H.

The key process giving rise to ventral furrow formation (VFF) in Drosophila embryo is apical constriction of cells in the ventral region. The constriction produces negative spontaneous curvature of the cell layer. During the initial slower phase of VFF approximately 40% of cells constrict in a seemingly random order. We show that this initial phase of VFF does not depend on random uncorrelated events. Instead, constricted cell apices form well-defined correlated structures, i.e., cellular constriction chains (CCCs), indicative of strong spatial and directional correlations between the constriction events. We argue that this chain formation is a signature of mechanical signaling that coordinates apical constrictions through tensile stress. To gain insights into the mechanisms involved in this correlated constriction process, we propose an active granular fluid (AGF) model which considers a tissue as a collection of mechanically active, stress-responsive objects. Our AGF molecular dynamics simulations show that cell constriction sensitivity to tensile stress results in formation of CCCs whereas compressive-stress sensitivity leads to compact constricted cell clusters; the CCCs, which can penetrate less-active regions, increase the robustness of the VFF process.

Damage in gamma titanium aluminides due to small particle impacts

NASA Astrophysics Data System (ADS)

Stief, P. S.; Rubal, M. P.; Gray, G. T., III; Pereiras, J. M.

1998-10-01

Initiation of cracking due to small particle impacts on low ductility intermetallics is investigated experimentally and theoretically. The gamma titanium aluminide alloys of interest which are being considered for elevated temperature structural applications in aircraft engines exhibit tensile ductilities on the order of 1-2%. Cracking due to any source, including small particle impacts, is of concern given the rapid growth of cracks in fatigue. This investigation focuses on a model geometry which reproduces the rear face cracking that is induced by a small particle impinging on an air foil leading edge. Small steel spheres are projected onto thin plates at velocities ranging from 76 to 305 ms ; cracking is thereby induced on the rear surface of the plates. Through finite element analyses of the dynamic impact event and some analytical estimates, we examine the hypothesis that crack initiation due to small particle impacts can be correlated with material ductility and with the severity and spatial extent of the straining during the impact event. In addition, with the use of static indentation tests in which similar strain distributions are present, some insight is gained into the difference in ductility between high and low strain rates. 1998 Elsevier Science Ltd.

Interaction rules for symbol-oriented graphical user interfaces

NASA Astrophysics Data System (ADS)

Brinkschulte, Uwe; Vogelsang, Holger; Wolf, Luc

1999-03-01

This work describes a way of interactive manipulation of structured objects by interaction rules. Symbols are used as graphical representation of object states. State changes lead to different visual symbol instances. The manipulation of symbols using interactive devices lead to an automatic state change of the corresponding structured object without any intervention of the application. Therefore, interaction rules are introduced. These rules describe the way a symbol may be manipulated and the effects this manipulation has on the corresponding structured object. The rules are interpreted by the visualization and interaction service. For each symbol used, a set of interaction rules can be defined. In order to be the more general as possible, all the interactions on a symbol are defined as a triple, which specifies the preconditions of all the manipulations of this symbol, the manipulations themselves, and the postconditions of all the manipulations of this symbol. A manipulation is a quintuplet, which describes the possible initial events of the manipulation, the possible places of these events, the preconditions of this manipulation, the results of this manipulation, and the postconditions of this manipulation. Finally, reflection functions map the results of a manipulation to the new state of a structured object.

Pathophysiology of wound healing and alterations in venous leg ulcers-review.

PubMed

Raffetto, Joseph D

2016-03-01

Venous leg ulcer (VLU) is one of the most common lower extremity ulcerated wound, and is a significant healthcare problem with implications that affect social, economic, and the well-being of a patient. VLU can have debilitating related problems which require weekly medical care and may take months to years to heal. The pathophysiology of VLU is complex, and healing is delayed in many patients due to a persistent inflammatory condition. Patient genetic and environmental factors predispose individuals to chronic venous diseases including VLU. Changes in shear stress affecting the glycocalyx are likely initiating events, leading to activation of adhesion molecules on endothelial cells, and leukocyte activation with attachment and migration into vein wall, microcirculation, and in the interstitial space. Multiple chemokines, cytokines, growth factors, proteases and matrix metalloproteinases are produced. The pathology of VLU involves an imbalance of inflammation, inflammatory modulators, oxidative stress, and proteinase activity. Understanding the cellular and biochemical events that lead to the progression of VLU is critical. With further understanding of inflammatory pathways and potential mechanisms, certain biomarkers could be revealed and studied as both involvement in the pathophysiology of VLU but also as therapeutic targets for VLU healing. © The Author(s) 2016.

Acute Kidney Injury before Dialysis Initiation Predicts Adverse Outcomes in Hemodialysis Patients.

PubMed

Lee, Timmy; Shah, Silvi; Leonard, Anthony C; Parikh, Pratik; Thakar, Charuhas V

2018-06-07

Acute kidney injury (AKI) is associated with increased morbidity and mortality. Mortality in end-stage renal disease (ESRD) patients is highest during the first year of dialysis. The impact of pre-ESRD AKI events on long-term outcomes in incident ESRD patients remains unknown. We evaluated a retrospective cohort of 47,341 incident hemodialysis patients from the United States Renal Data System with linked Medicare data for at least 2 years prior to hemodialysis initiation. We examined the impact of pre-ESRD AKI events in the 2-year pre-ESRD period on the type of vascular access used at hemodialysis initiation (central venous catheter (CVC) versus arteriovenous access), and 1-year all-cause mortality after initiating hemodialysis. The mean age was 72 ± 11 years. Of the study cohort, 18% initiated hemodialysis with arteriovenous access, and 54% of patients had at least one pre-ESRD AKI event. One-year, all-cause mortality was 32%. Compared to 75% for patients without a pre-ESRD AKI event, 89% of patients with a pre-ESRD AKI event initiated hemodialysis with CVC than arteriovenous access (p < 0.001). A pre-ESRD AKI event was associated with lower adjusted odds of starting hemodialysis with an arteriovenous access (OR 0.47; 95% CI 0.44-0.50, p < 0.001), and higher adjusted odds of 1-year mortality (OR 1.36; 95% CI 1.30-1.42, p < 0.001). An AKI event prior to initiating hemodialysis independently increases the risk of CVC use and predicts 1-year mortality. Improving processes of care after AKI events may improve dialysis outcomes in patients who progress to ESRD. © 2018 S. Karger AG, Basel.

Optical rogue waves and stimulated supercontinuum generation

NASA Astrophysics Data System (ADS)

Solli, Daniel R.; Ropers, Claus; Jalali, Bahram

2010-06-01

Nonlinear action is known for its ability to create unusual phenomena and unexpected events. Optical rogue waves-freak pulses of broadband light arising in nonlinear fiber-testify to the fact that optical nonlinearities are no less capable of generating anomalous events than those in other physical contexts. In this paper, we will review our work on optical rogue waves, an ultrafast phenomenon counterpart to the freak ocean waves known to roam the open oceans. We will discuss the experimental observation of these rare events in real time and the measurement of their heavytailed statistical properties-a probabilistic form known to appear in a wide variety of other complex systems from financial markets to genetics. The nonlinear Schrödinger equation predicts the existence of optical rogue waves, offering a means to study their origins with simulations. We will also discuss the type of initial conditions behind optical rogue waves. Because a subtle but specific fluctuation leads to extreme waves, the rogue wave instability can be harnessed to produce these events on demand. By exploiting this property, it is possible to produce a new type of optical switch as well as a supercontinuum source that operates in the long pulse regime but still achieves a stable, coherent output.

Uranium isotope evidence for two episodes of deoxygenation during Oceanic Anoxic Event 2

NASA Astrophysics Data System (ADS)

Clarkson, Matthew O.; Stirling, Claudine H.; Jenkyns, Hugh C.; Dickson, Alexander J.; Porcelli, Don; Moy, Christopher M.; Pogge von Strandmann, Philip A. E.; Cooke, Ilsa R.; Lenton, Timothy M.

2018-03-01

Oceanic Anoxic Event 2 (OAE 2), occurring ˜94 million years ago, was one of the most extreme carbon cycle and climatic perturbations of the Phanerozoic Eon. It was typified by a rapid rise in atmospheric CO2, global warming, and marine anoxia, leading to the widespread devastation of marine ecosystems. However, the precise timing and extent to which oceanic anoxic conditions expanded during OAE 2 remains unresolved. We present a record of global ocean redox changes during OAE 2 using a combined geochemical and carbon cycle modeling approach. We utilize a continuous, high-resolution record of uranium isotopes in pelagic and platform carbonate sediments to quantify the global extent of seafloor anoxia during OAE 2. This dataset is then compared with a dynamic model of the coupled global carbon, phosphorus, and uranium cycles to test hypotheses for OAE 2 initiation. This unique approach highlights an intra-OAE complexity that has previously been underconstrained, characterized by two expansions of anoxia separated by an episode of globally significant reoxygenation coincident with the “Plenus Cold Event.” Each anoxic expansion event was likely driven by rapid atmospheric CO2 injections from multiphase Large Igneous Province activity.

Consensus Recommendations on Training and Competing in the Heat.

PubMed

Racinais, Sébastien; Alonso, Juan-Manuel; Coutts, Aaron J; Flouris, Andreas D; Girard, Olivier; González-Alonso, José; Hausswirth, Christophe; Jay, Ollie; Lee, Jason K W; Mitchell, Nigel; Nassis, George P; Nybo, Lars; Pluim, Babette M; Roelands, Bart; Sawka, Michael N; Wingo, Jonathan; Périard, Julien D

2015-07-01

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimize performance is to heat acclimatize. Heat acclimatization should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in an euhydrated state and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vests), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimizing the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events for hydration and body cooling opportunities when competitions are held in the heat.

Observation of a centrality-dependent dijet asymmetry in lead-lead collisions at sqrt[S(NN)] =2.76 TeV with the ATLAS detector at the LHC.

PubMed

Aad, G; Abbott, B; Abdallah, J; Abdelalim, A A; Abdesselam, A; Abdinov, O; Abi, B; Abolins, M; Abramowicz, H; Abreu, H; Acerbi, E; Acharya, B S; Ackers, M; Adams, D L; Addy, T N; Adelman, J; Aderholz, M; Adomeit, S; Adragna, P; Adye, T; Aefsky, S; Aguilar-Saavedra, J A; Aharrouche, M; Ahlen, S P; Ahles, F; Ahmad, A; Ahsan, M; Aielli, G; Akdogan, T; Akesson, T P A; Akimoto, G; Akimov, A V; Alam, M S; Alam, M A; Albrand, S; Aleksa, M; Aleksandrov, I N; Aleppo, M; Alessandria, F; Alexa, C; Alexander, G; Alexandre, G; Alexopoulos, T; Alhroob, M; Aliev, M; Alimonti, G; Alison, J; Aliyev, M; Allport, P P; Allwood-Spiers, S E; Almond, J; Aloisio, A; Alon, R; Alonso, A; Alonso, J; Alviggi, M G; Amako, K; Amaral, P; Amelung, C; Ammosov, V V; Amorim, A; Amorós, G; Amram, N; Anastopoulos, C; Andeen, T; Anders, C F; Anderson, K J; Andreazza, A; Andrei, V; Andrieux, M-L; Anduaga, X S; Angerami, A; Anghinolfi, F; Anjos, N; Annovi, A; Antonaki, A; Antonelli, M; Antonelli, S; Antos, J; Anulli, F; Aoun, S; Bella, L Aperio; Apolle, R; Arabidze, G; Aracena, I; Arai, Y; Arce, A T H; Archambault, J P; Arfaoui, S; Arguin, J-F; Arik, E; Arik, M; Armbruster, A J; Arms, K E; Armstrong, S R; Arnaez, O; Arnault, C; Artamonov, A; Artoni, G; Arutinov, D; Asai, S; Silva, J; Asfandiyarov, R; Ask, S; Asman, B; Asquith, L; Assamagan, K; Astbury, A; Astvatsatourov, A; Atoian, G; Aubert, B; Auerbach, B; Auge, E; Augsten, K; Aurousseau, M; Austin, N; Avramidou, R; Axen, D; Ay, C; Azuelos, G; Azuma, Y; Baak, M A; Baccaglioni, G; Bacci, C; Bach, A M; Bachacou, H; Bachas, K; Bachy, G; Backes, M; Badescu, E; Bagnaia, P; Bahinipati, S; Bai, Y; Bailey, D C; Bain, T; Baines, J T; Baker, O K; Baker, S; Pedrosa, F Baltasar Dos Santos; Banas, E; Banerjee, P; Banerjee, Sw; Banfi, D; Bangert, A; Bansal, V; Bansil, H S; Barak, L; Baranov, S P; Barashkou, A; Galtieri, A Barbaro; Barber, T; Barberio, E L; Barberis, D; Barbero, M; Bardin, D Y; Barillari, T; Barisonzi, M; Barklow, T; Barlow, N; Barnett, B M; Barnett, R M; 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Torrence, E; Pastor, E Torró; Toth, J; Touchard, F; Tovey, D R; Traynor, D; Trefzger, T; Treis, J; Tremblet, L; Tricoli, A; Trigger, I M; Trincaz-Duvoid, S; Trinh, T N; Tripiana, M F; Triplett, N; Trischuk, W; Trivedi, A; Trocmé, B; Troncon, C; Trottier-McDonald, M; Trzupek, A; Tsarouchas, C; Tseng, J C-L; Tsiakiris, M; Tsiareshka, P V; Tsionou, D; Tsipolitis, G; Tsiskaridze, V; Tskhadadze, E G; Tsukerman, I I; Tsulaia, V; Tsung, J-W; Tsuno, S; Tsybychev, D; Tua, A; Tuggle, J M; Turala, M; Turecek, D; Cakir, I Turk; Turlay, E; Tuts, P M; Tykhonov, A; Tylmad, M; Tyndel, M; Typaldos, D; Tyrvainen, H; Tzanakos, G; Uchida, K; Ueda, I; Ueno, R; Ugland, M; Uhlenbrock, M; Uhrmacher, M; Ukegawa, F; Unal, G; Underwood, D G; Undrus, A; Unel, G; Unno, Y; Urbaniec, D; Urkovsky, E; Urquijo, P; Urrejola, P; Usai, G; Uslenghi, M; Vacavant, L; Vacek, V; Vachon, B; Vahsen, S; Valderanis, C; Valenta, J; Valente, P; Valentinetti, S; Valkar, S; Gallego, E Valladolid; Vallecorsa, S; Ferrer, J A Valls; van der Graaf, H; van der Kraaij, E; van der Poel, E; van der Ster, D; Van Eijk, B; van Eldik, N; van Gemmeren, P; van Kesteren, Z; van Vulpen, I; Vandelli, W; Vandoni, G; Vaniachine, A; Vankov, P; Vannucci, F; Rodriguez, F Varela; Vari, R; Varnes, E W; Varouchas, D; Vartapetian, A; Varvell, K E; Vassilakopoulos, V I; Vazeille, F; Vegni, G; Veillet, J J; Vellidis, C; Veloso, F; Veness, R; Veneziano, S; Ventura, A; Ventura, D; Ventura, S; Venturi, M; Venturi, N; Vercesi, V; Verducci, M; Verkerke, W; Vermeulen, J C; Vest, A; Vetterli, M C; Vichou, I; Vickey, T; Viehhauser, G H A; Viel, S; Villa, M; Perez, M Villaplana; Vilucchi, E; Vincter, M G; Vinek, E; Vinogradov, V B; Virchaux, M; Viret, S; Virzi, J; Vitale, A; Vitells, O; Vivarelli, I; Vaque, F Vives; Vlachos, S; Vlasak, M; Vlasov, N; Vogel, A; Vokac, P; Volpi, M; Volpini, G; von der Schmitt, H; von Loeben, J; von Radziewski, H; von Toerne, E; Vorobel, V; Vorobiev, A P; Vorwerk, V; Vos, M; Voss, R; Voss, T T; Vossebeld, J H; Vovenko, A S; Vranjes, N; Milosavljevic, M Vranjes; Vrba, V; Vreeswijk, M; Anh, T Vu; Vuillermet, R; Vukotic, I; Wagner, W; Wagner, P; Wahlen, H; Wakabayashi, J; Walbersloh, J; Walch, S; Walder, J; Walker, R; Walkowiak, W; Wall, R; Waller, P; Wang, C; Wang, H; Wang, J; Wang, J; Wang, J C; Wang, S M; Warburton, A; Ward, C P; Warsinsky, M; Watkins, P M; Watson, A T; Watson, M F; Watts, G; Watts, S; Waugh, A T; Waugh, B M; Weber, J; Weber, M; Weber, M S; Weber, P; Weidberg, A R; Weingarten, J; Weiser, C; Wellenstein, H; Wells, P S; Wen, M; Wenaus, T; Wendler, S; Weng, Z; Wengler, T; Wenig, S; Wermes, N; Werner, M; Werner, P; Werth, M; Wessels, M; Whalen, K; Wheeler-Ellis, S J; Whitaker, S P; White, A; White, M J; White, S; Whitehead, S R; Whiteson, D; Whittington, D; Wicek, F; Wicke, D; Wickens, F J; Wiedenmann, W; Wielers, M; Wienemann, P; Wiglesworth, C; Wiik, L A M; Wildauer, A; Wildt, M A; Wilhelm, I; Wilkens, H G; Will, J Z; Williams, E; Williams, H H; Willis, W; Willocq, S; Wilson, J A; Wilson, M G; Wilson, A; Wingerter-Seez, I; Winkelmann, S; Winklmeier, F; Wittgen, M; Wolter, M W; Wolters, H; Wooden, G; Wosiek, B K; Wotschack, J; Woudstra, M J; Wraight, K; Wright, C; Wrona, B; Wu, S L; Wu, X; Wulf, E; Wunstorf, R; Wynne, B M; Xaplanteris, L; Xella, S; Xie, S; Xie, Y; Xu, C; Xu, D; Xu, G; Yabsley, B; Yamada, M; Yamamoto, A; Yamamoto, K; Yamamoto, S; Yamamura, T; Yamaoka, J; Yamazaki, T; Yamazaki, Y; Yan, Z; Yang, H; Yang, U K; Yang, Y; Yang, Y; Yang, Z; Yanush, S; Yao, W-M; Yao, Y; Yasu, Y; Ye, J; Ye, S; Yilmaz, M; Yoosoofmiya, R; Yorita, K; Yoshida, R; Young, C; Youssef, S P; Yu, D; Yu, J; Yu, J; Yuan, L; Yurkewicz, A; Zaets, V G; Zaidan, R; Zaitsev, A M; Zajacova, Z; Zalite, Yo K; Zanello, L; Zarzhitsky, P; Zaytsev, A; Zdrazil, M; Zeitnitz, C; Zeller, M; Zema, P F; Zemla, A; Zendler, C; Zenin, A V; Zenin, O; Zeniš, T; Zenonos, Z; Zenz, S; Zerwas, D; Della Porta, G Zevi; Zhan, Z; Zhang, H; Zhang, J; Zhang, X; Zhang, Z; Zhao, L; Zhao, T; Zhao, Z; Zhemchugov, A; Zheng, S; Zhong, J; Zhou, B; Zhou, N; Zhou, Y; Zhu, C G; Zhu, H; Zhu, Y; Zhuang, X; Zhuravlov, V; Zieminska, D; Zilka, B; Zimmermann, R; Zimmermann, S; Zimmermann, S; Ziolkowski, M; Zitoun, R; Zivković, L; Zmouchko, V V; Zobernig, G; Zoccoli, A; Zolnierowski, Y; Zsenei, A; zur Nedden, M; Zutshi, V; Zwalinski, L

2010-12-17

By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Synoptic Regulation of The 3 May 1999 Oklahoma Tornado Outbreak

NASA Astrophysics Data System (ADS)

Schultz, D. M.; Roebber, P. J.; Romero, R.

Despite the relatively successful long-lead-time forecasts of the storms during the 3 May 1999 tornadic outbreak in Oklahoma and Kansas, forecasters were unable to predict with confidence details concerning convective initiation and convective mode. The forecasters identified three synoptic processes they were monitoring for clues as to how the event would unfold. These elements were (a) the absence of strong surface convergence along a dryline in western Oklahoma and the Texas panhandle, (b) the presence of a cirrus shield that was hypothesized to limit surface heating, and (c) the arrival into Oklahoma of an upper-level wind-speed maximum (associated with the so- called southern PV anomaly) that was responsible for favorable synoptic-scale ascent and the cirrus shield. The Pennsylvania State University/National Center for Atmospheric Research Mesoscale Model Version 5 (MM5) is used in forecast mode (using the operational AVN run data to provide initial and lateral boundary conditions) to explore the sen- sitivity of the outbreak to these features using simulations down to 2-km horizontal grid spacing. A 30-h control simulation is compared to the available observations and captures important qualitative characteristics of the event, including convective initi- ation east of the dryline and organization of mesoscale convective systems into long lived, long-track supercells. Additional simulations in which the initial strength of the southern PV anomaly is altered suggest that synoptic regulation of the 3 May 1999 event was imposed by the effects of the southern PV anomaly. The model results in- dicate that: (1) convective initiation in the weakly forced environment was achieved through modification of the existing cap through both surface heating and synoptic- scale ascent associated with the southern PV anomaly; (2) supercellular organization was supported regardless of the strength of the southern PV anomaly, although weak- to-moderate forcing from this feature was most conducive to the production of long lived supercells and strong forcing resulted in a trend toward linear mesoscale convec- tive systems; (3) the cirrus shield was important in limiting development of convection and reducing competition between storms.

Community nurse-led initiation of antiviral therapy for chronic hepatitis C in people who inject drugs does not increase uptake of or adherence to treatment.

PubMed

Lewis, Heather; Kunkel, Jan; Axten, David; Dalton, Jane; Gardner, Hayley; Tippett, Andrew; Wynne, Stephanie; Wilkinson, Mandie; Foster, Graham R

2016-11-01

Chronic hepatitis C is common in people who inject drugs (PWID) and this population serves as a reservoir for infection. Treatment levels are low among this group, ranging from 1 to 19%. We explored whether a nurse-initiated community treatment model increased uptake of and adherence to interferon-based therapies. This was a cluster randomized trial of nurse-initiated versus physician-initiated antiviral therapy with pegylated interferon and ribavirin for hepatitis C virus in community clinics (trial registration: ISRCTN07774040). The proportion of participants initiating treatment during follow-up was 10% with nurse-initiated (6/62) and 9% with physician-initiated (6/76) therapy. Adherence was similar in both groups, with only one patient in each arm not adhering to therapy. There were no serious adverse events, but interferon-related side effects were common. Drug and alcohol use did not change during therapy. Despite easy access to antiviral therapy, uptake of treatment was poor, with no significant difference between the groups. Nurse-led initiation of interferon-based antiviral therapy in PWID did not lead to increased uptake of, response to or adherence with treatment. Further service improvement is unlikely to increase the proportion of PWID undergoing antiviral therapy for hepatitis C virus and early adoption of interferon-free regimens may increase the proportion initiating and completing treatment.

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

DOE PAGES

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn; ...

2017-11-27

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

Importance of initial and final state effects for azimuthal correlations in p + Pb collisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Greif, Moritz; Greiner, Carsten; Schenke, Bjorn

In this work, we investigate the relative importance of initial and final state effects on azimuthal correlations of gluons in low and high multiplicity p+Pb collisions. To achieve this, we couple Yang-Mills dynamics of pre-equilibrium gluon fields (IP-GLASMA) to a perturbative QCD based parton cascade for the final state evolution (BAMPS) on an event-by-event basis. We find that signatures of both the initial state correlations and final state interactions are seen in azimuthal correlation observables, such as v 2 {2PC} (p T), their strength depending on the event multiplicity and transverse momentum. Initial state correlations dominate v 2 {2PC} (pmore » T) in low multiplicity events for transverse momenta p T > 2 GeV. Lastly, while final state interactions are dominant in high multiplicity events, initial state correlations affect v 2 {2PC} (p T) for p T > 2 GeV as well as the pT integrated v 2 {2PC}.« less

Human visual response to nuclear particle exposures

NASA Technical Reports Server (NTRS)

Tobias, C. A.; Budinger, T. F.; Lyman, J. T.

1972-01-01

Experiments with accelerated helium ions were performed in an effort to localize the site of initial radiation interactions in the eye that lead to light flash observations by astronauts during spaceflight. The character and efficiency of helium ion induction of visual sensations depended on the state of dark adaptation of the retina; also, the same events were seen with different efficiencies and details when particle flux density changed. It was concluded that fast particles cause interactions in the retina, particularly in the receptor layer, and thus give rise to the sensations of light flashes, streaks, and supernovae.

Mod-2 wind turbine project assessment and cluster test plans

NASA Technical Reports Server (NTRS)

Gordon, L. H.

1982-01-01

An assessment of the Mod-2 Wind Turbine project is presented based on initial goals and present results. Specifically, the Mod-2 background, project flow, and a chronology of events/results leading to Mod-2 acceptance is presented. After checkout/acceptance of the three operating turbines, NASA/LeRC will continue management of a two year test program performed at the DOE Goodnoe Hills test site. This test program is expected to yield data necessary for the continued development and optimization of wind energy systems. These test activities, the implementation of, and the results to date are also presented.

CONSOLIDATING AND CRUSHING EXOPLANETS: DID IT HAPPEN HERE?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Volk, Kathryn; Gladman, Brett

2015-06-20

The Kepler mission results indicate that systems of tightly packed inner planets (STIPs) are present around of order 5% of FGK field stars (whose median age is ∼5 Gyr). We propose that STIPs initially surrounded nearly all such stars, and those observed are the final survivors of a process in which long-term metastability eventually ceases and the systems proceed to collisional consolidation or destruction, losing roughly equal fractions of systems every decade in time. In this context, we also propose that our solar system initially contained additional large planets interior to the current orbit of Venus, which survived in amore » metastable dynamical configuration for 1%–10% of the solar system’s age. Long-term gravitational perturbations caused the system orbits to cross, leading to a cataclysmic event that left Mercury as the sole surviving relic.« less

Directional Characteristics of Inner Shelf Internal Tides

DTIC Science & Technology

2007-06-01

Figure 18. YD 202-206 Current vector plot of significant events. Significant events include internal tidal bores, solibores, and solitons . The upper...Events (Bores, Solibores, and Solitons ): Upper column leading-edge cross-shore current velocity and cross-shore wind regression. The small ellipse...Significant Events (Bores, Solibores, and Solitons ): Upper column leading-edge along-shore current velocity and along-shore wind regression. The small

Long-term mipomersen treatment is associated with a reduction in cardiovascular events in patients with familial hypercholesterolemia.

PubMed

Duell, P Barton; Santos, Raul D; Kirwan, Bridget-Anne; Witztum, Joseph L; Tsimikas, Sotirios; Kastelein, John J P

2016-01-01

Familial hypercholesterolemia (FH) is characterized by severely elevated LDL-cholesterol and up to a 20-fold increase in premature cardiovascular disease (CVD). Mipomersen has been shown to lower the levels of these atherogenic lipoproteins, but whether it lowers major adverse cardiac events (MACEs) has not been addressed. This post hoc analysis of prospectively collected data of three randomized trials and an open-label extension phase included patients that were exposed to ≥12 months of mipomersen. MACE rates that occurred during 24 months before randomization in the mipomersen group were compared to MACE rates after initiation of mipomersen. Data from the trials included in this report are registered in Clinicaltrials.gov (NCT00607373, NCT00706849, NCT00794664, NCT00694109). The occurrence of MACE events, defined as cardiovascular death, nonfatal acute myocardial infarction, hospitalization for unstable angina, coronary revascularization and nonfatal ischemic stroke, was obtained from medical history data pre-treatment and adjudicated by an independent adjudication committee for events occurring post-treatment with mipomersen. MACEs were identified in 61.5% of patients (64 patients with 146 events [39 myocardial infarctions, 99 coronary revascularizations, 5 unstable angina episodes, 3 ischemic strokes]) during 24 months before mipomersen treatment, and in 9.6% of patients (10 patients with 13 events [1 cardiovascular death, 2 myocardial infarctions, 6 coronary interventions, 4 unstable angina episodes]) during a mean of 24.4 months after initiation of mipomersen (MACE rate 25.7 of 1000 patient-months vs 3.9 of 1000 patient-months, OR = 0.053 [95% CI, 0.016-0.168], P < .0001 by the exact McNemar test). The reduction in MACE coincided with a mean absolute reduction in LDL-C of 70 mg/dL (-28%) and of non-HDL cholesterol of 74 mg/dL (-26%) as well as reduction in Lp(a) of 11 mg/dL (-17%). Long-term mipomersen treatment not only lowers levels of atherogenic lipoproteins but may also lead to a reduction in cardiovascular events in FH patients. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Rates and Reasons for Early Change of First HAART in HIV-1-Infected Patients in 7 Sites throughout the Caribbean and Latin America

PubMed Central

Cesar, Carina; Shepherd, Bryan E.; Krolewiecki, Alejandro J.; Fink, Valeria I.; Schechter, Mauro; Tuboi, Suely H.; Wolff, Marcelo; Pape, Jean W.; Leger, Paul; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; Sued, Omar; McGowan, Catherine C.; Masys, Daniel R.; Cahn, Pedro E.

2010-01-01

Background HAART rollout in Latin America and the Caribbean has increased from approximately 210,000 in 2003 to 390,000 patients in 2007, covering 62% (51%–70%) of eligible patients, with considerable variation among countries. No multi-cohort study has examined rates of and reasons for change of initial HAART in this region. Methodology Antiretroviral-naïve patients > = 18 years who started HAART between 1996 and 2007 and had at least one follow-up visit from sites in Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru were included. Time from HAART initiation to change (stopping or switching any antiretrovirals) was estimated using Kaplan-Meier techniques. Cox proportional hazards modeled the associations between change and demographics, initial regimen, baseline CD4 count, and clinical stage. Principal Findings Of 5026 HIV-infected patients, 35% were female, median age at HAART initiation was 37 years (interquartile range [IQR], 31–44), and median CD4 count was 105 cells/uL (IQR, 38–200). Estimated probabilities of changing within 3 months and one year of HAART initiation were 16% (95% confidence interval (CI) 15–17%) and 28% (95% CI 27–29%), respectively. Efavirenz-based regimens and no clinical AIDS at HAART initiation were associated with lower risk of change (hazard ratio (HR) = 1.7 (95% CI 1.1–2.6) and 2.1 (95% CI 1.7–2.5) comparing neverapine-based regimens and other regimens to efavirenz, respectively; HR = 1.3 (95% CI 1.1–1.5) for clinical AIDS at HAART initiation). The primary reason for change among HAART initiators were adverse events (14%), death (5.7%) and failure (1.3%) with specific toxicities varying among sites. After change, most patients remained in first line regimens. Conclusions Adverse events were the leading cause for changing initial HAART. Predictors for change due to any reason were AIDS at baseline and the use of a non-efavirenz containing regimen. Differences between participant sites were observed and require further investigation. PMID:20531956

Familial polycystic ovarian disease.

PubMed

Givens, J R

1988-12-01

Emphasis is placed on the heterogeneity of the phenotypic presentation of PCOD. It is the common expression of an unknown number of disorders and thus is a sign and not a specific diagnosis. Two essential features are arrested follicular maturation and atresia of follicles. Normal folliculogenesis is described, emphasizing that a large number of areas could be subject to derangement causing PCOD. Any interference of the finely balanced sequence of events can lead to PCOD. The genetic defect causing familial PCOD is unknown and the initiating event remains undefined. Three families are described that illustrate four features of familial PCOD. A number of associated disorders such as diabetes, hyperinsulinemia, obesity, and hypertension are described. The potential importance of agents that modulate the LH and FSH activity that may cause PCOD is emphasized. The theoretic means by which similar male and female gonadal abnormalities may be coupled in families through growth factors EGF and alpha TGF are presented.

ENSO-based probabilistic forecasts of March-May U.S. tornado and hail activity

NASA Astrophysics Data System (ADS)

Lepore, Chiara; Tippett, Michael K.; Allen, John T.

2017-09-01

Extended logistic regression is used to predict March-May severe convective storm (SCS) activity based on the preceding December-February (DJF) El Niño-Southern Oscillation (ENSO) state. The spatially resolved probabilistic forecasts are verified against U.S. tornado counts, hail events, and two environmental indices for severe convection. The cross-validated skill is positive for roughly a quarter of the U.S. Overall, indices are predicted with more skill than are storm reports, and hail events are predicted with more skill than tornado counts. Skill is higher in the cool phase of ENSO (La Niña like) when overall SCS activity is higher. SCS forecasts based on the predicted DJF ENSO state from coupled dynamical models initialized in October of the previous year extend the lead time with only a modest reduction in skill compared to forecasts based on the observed DJF ENSO state.

Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea.

PubMed

Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Geo, Jini; Dilipkumar, Shilpa; Pasricha, Renu; Gulyani, Akash; Raghavan, Srikala; Palakodeti, Dasaradhi

2017-09-01

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1 , are translationally regulated by SMED-PABPC2 . Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration. © 2017. Published by The Company of Biologists Ltd.

Cytoplasmic poly (A)-binding protein critically regulates epidermal maintenance and turnover in the planarian Schmidtea mediterranea

PubMed Central

Bansal, Dhiru; Kulkarni, Jahnavi; Nadahalli, Kavana; Lakshmanan, Vairavan; Krishna, Srikar; Sasidharan, Vidyanand; Dilipkumar, Shilpa; Gulyani, Akash; Raghavan, Srikala

2017-01-01

Identifying key cellular events that facilitate stem cell function and tissue organization is crucial for understanding the process of regeneration. Planarians are powerful model system to study regeneration and stem cell (neoblast) function. Here, using planaria, we show that the initial events of regeneration, such as epithelialization and epidermal organization are critically regulated by a novel cytoplasmic poly A-binding protein, SMED-PABPC2. Knockdown of smed-pabpc2 leads to defects in epidermal lineage specification, disorganization of epidermis and ECM, and deregulated wound healing, resulting in the selective failure of neoblast proliferation near the wound region. Polysome profiling suggests that epidermal lineage transcripts, including zfp-1, are translationally regulated by SMED-PABPC2. Together, our results uncover a novel role for SMED-PABPC2 in the maintenance of epidermal and ECM integrity, critical for wound healing and subsequent processes for regeneration. PMID:28807897

A MODEL FOR MAGNETICALLY COUPLED SYMPATHETIC ERUPTIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toeroek, T.; Titov, V. S.; Mikic, Z.

2011-10-01

Sympathetic eruptions on the Sun have been observed for several decades, but the mechanisms by which one eruption can trigger another remain poorly understood. We present a three-dimensional MHD simulation that suggests two possible magnetic trigger mechanisms for sympathetic eruptions. We consider a configuration that contains two coronal flux ropes located within a pseudo-streamer and one rope located next to it. A sequence of eruptions is initiated by triggering the eruption of the flux rope next to the streamer. The expansion of the rope leads to two consecutive reconnection events, each of which triggers the eruption of a flux ropemore » by removing a sufficient amount of overlying flux. The simulation qualitatively reproduces important aspects of the global sympathetic event on 2010 August 1 and provides a scenario for the so-called twin filament eruptions. The suggested mechanisms are also applicable for sympathetic eruptions occurring in other magnetic configurations.« less

A statistical framework for evaluating neural networks to predict recurrent events in breast cancer

NASA Astrophysics Data System (ADS)

Gorunescu, Florin; Gorunescu, Marina; El-Darzi, Elia; Gorunescu, Smaranda

2010-07-01

Breast cancer is the second leading cause of cancer deaths in women today. Sometimes, breast cancer can return after primary treatment. A medical diagnosis of recurrent cancer is often a more challenging task than the initial one. In this paper, we investigate the potential contribution of neural networks (NNs) to support health professionals in diagnosing such events. The NN algorithms are tested and applied to two different datasets. An extensive statistical analysis has been performed to verify our experiments. The results show that a simple network structure for both the multi-layer perceptron and radial basis function can produce equally good results, not all attributes are needed to train these algorithms and, finally, the classification performances of all algorithms are statistically robust. Moreover, we have shown that the best performing algorithm will strongly depend on the features of the datasets, and hence, there is not necessarily a single best classifier.

An exemplary developing astronomy movement in Nepal

NASA Astrophysics Data System (ADS)

Neupane, Sudeep

2015-03-01

Astronomy and space science education had been given least importance by Nepalese government in the past. The modern astronomy movement is believed to have started when an official observation programme of Haley's comet was organized by Royal Nepal Academy of Science and Technology (RONAST) in 1986. Following the huge pressure from the scientific community, the Nepal government (Kingdom of Nepal at that time) established B.P. Koirala Memorial Planetarium, Observatory and Science Museum Development Board in 1992. Initiatives of the project started with observatory set up and the development of astrophysics syllabus for university students. Astrophysics is included as an elective paper in the Physics masters course. The lead astrophysicist of Nepal Dr. Binil Aryal is running a research group in Tribhuvan University since 2005 which has a significant number of international publications. The developing government initiatives and achievements will be discussed. In 2007, a group of astronomy enthusiastic students along with amateurs working independently in past established Nepal Astronomical Society (NASO), which surprisingly increased the amateur activities and inspired other amateur groups to revive. During IYA 2009, more than 80 outreach and observation events were organized solely by NASO. NASO was able to collaborate with many international programmes and projects like GHOU/GTTP, EurAstro, AWB, UNAWE, SGAC, Star Peace, TWAN etc during and beyond IYA2009. Currently Nepal is recognized as the most eventful country of outreach and astronomy education among the amateur community. The success story of the astronomy movement and the local difficulties while organizing the events will be explained.

ADAPT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reynolds, John; Jankovsky, Zachary; Metzroth, Kyle G

2018-04-04

The purpose of the ADAPT code is to generate Dynamic Event Trees (DET) using a user specified set of simulators. ADAPT can utilize any simulation tool which meets a minimal set of requirements. ADAPT is based on the concept of DET which uses explicit modeling of the deterministic dynamic processes that take place during a nuclear reactor plant system (or other complex system) evolution along with stochastic modeling. When DET are used to model various aspects of Probabilistic Risk Assessment (PRA), all accident progression scenarios starting from an initiating event are considered simultaneously. The DET branching occurs at user specifiedmore » times and/or when an action is required by the system and/or the operator. These outcomes then decide how the dynamic system variables will evolve in time for each DET branch. Since two different outcomes at a DET branching may lead to completely different paths for system evolution, the next branching for these paths may occur not only at separate times, but can be based on different branching criteria. The computational infrastructure allows for flexibility in ADAPT to link with different system simulation codes, parallel processing of the scenarios under consideration, on-line scenario management (initiation as well as termination), analysis of results, and user friendly graphical capabilities. The ADAPT system is designed for a distributed computing environment; the scheduler can track multiple concurrent branches simultaneously. The scheduler is modularized so that the DET branching strategy can be modified (e.g. biasing towards the worst-case scenario/event). Independent database systems store data from the simulation tasks and the DET structure so that the event tree can be constructed and analyzed later. ADAPT is provided with a user-friendly client which can easily sort through and display the results of an experiment, precluding the need for the user to manually inspect individual simulator runs.« less

Electron Tomography Reveals the Steps in Filovirus Budding

PubMed Central

Welsch, Sonja; Kolesnikova, Larissa; Krähling, Verena; Riches, James D.; Becker, Stephan; Briggs, John A. G.

2010-01-01

The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a “submarine-like” budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular “rocket-like” protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses. PMID:20442788

Lessons learnt from Dental Patient Safety Case Reports

PubMed Central

Obadan, Enihomo M.; Ramoni, Rachel B.; Kalenderian, Elsbeth

2015-01-01

Background Errors are commonplace in dentistry, it is therefore our imperative as dental professionals to intercept them before they lead to an adverse event, and/or mitigate their effects when an adverse event occurs. This requires a systematic approach at both the profession-level, encapsulated in the Agency for Healthcare Research and Quality’s Patient Safety Initiative structure, as well as at the practice-level, where Crew Resource Management is a tested paradigm. Supporting patient safety at both the dental practice and profession levels relies on understanding the types and causes of errors, an area in which little is known. Methods A retrospective review of dental adverse events reported in the literature was performed. Electronic bibliographic databases were searched and data were extracted on background characteristics, incident description, case characteristics, clinic setting where adverse event originated, phase of patient care that adverse event was detected, proximal cause, type of patient harm, degree of harm and recovery actions. Results 182 publications (containing 270 cases) were identified through our search. Delayed and unnecessary treatment/disease progression after misdiagnosis was the largest type of harm reported. 24.4% of reviewed cases were reported to have experienced permanent harm. One of every ten case reports reviewed (11.1%) reported that the adverse event resulted in the death of the affected patient. Conclusions Published case reports provide a window into understanding the nature and extent of dental adverse events, but for as much as the findings revealed about adverse events, they also identified the need for more broad-based contributions to our collective body of knowledge about adverse events in the dental office and their causes. Practical Implications Siloed and incomplete contributions to our understanding of adverse events in the dental office are threats to dental patients’ safety. PMID:25925524

Measurement of the correlation between flow harmonics of different order in lead-lead collisions at √s NN = 2.76 TeV with the ATLAS detector

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aad, G.

2015-09-14

Correlations between the elliptic or triangular flow coefficients v m (m=2 or 3) and other flow harmonics v n (n=2 to 5) are measured using √s NN=2.76 TeV Pb+Pb collision data collected in 2010 by the ATLAS experiment at the LHC, corresponding to an integrated luminosity of 7 μb -1. The v m-v n correlations are measured in midrapidity as a function of centrality, and, for events within the same centrality interval, as a function of event ellipticity or triangularity defined in a forward rapidity region. For events within the same centrality interval, v 3 is found to be anticorrelatedmore » with v 2 and this anticorrelation is consistent with similar anticorrelations between the corresponding eccentricities, ε 2 and ε 3. However, it is observed that v 4 increases strongly with v 2, and v 5 increases strongly with both v 2 and v 3. The trend and strength of the vm-vn correlations for n=4 and 5 are found to disagree with ε m-ε n correlations predicted by initial-geometry models. Instead, these correlations are found to be consistent with the combined effects of a linear contribution to vn and a nonlinear term that is a function of v 2 2 or of v 2v 3, as predicted by hydrodynamic models. A simple two-component fit is used to separate these two contributions. The extracted linear and nonlinear contributions to v 4 and v 5 are found to be consistent with previously measured event-plane correlations.« less

RAS Initiative - Events

Cancer.gov

The NCI RAS Initiative has organized multiple events with outside experts to discuss how the latest scientific and technological breakthroughs can be applied to discover vulnerabilities in RAS-driven cancers.

Calibration of a rainfall-runoff hydrological model and flood simulation using data assimilation

NASA Astrophysics Data System (ADS)

Piacentini, A.; Ricci, S. M.; Thual, O.; Coustau, M.; Marchandise, A.

2010-12-01

Rainfall-runoff models are crucial tools for long-term assessment of flash floods or real-time forecasting. This work focuses on the calibration of a distributed parsimonious event-based rainfall-runoff model using data assimilation. The model combines a SCS-derived runoff model and a Lag and Route routing model for each cell of a regular grid mesh. The SCS-derived runoff model is parametrized by the initial water deficit, the discharge coefficient for the soil reservoir and a lagged discharge coefficient. The Lag and Route routing model is parametrized by the velocity of travel and the lag parameter. These parameters are assumed to be constant for a given catchment except for the initial water deficit and the velocity travel that are event-dependent (landuse, soil type and moisture initial conditions). In the present work, a BLUE filtering technique was used to calibrate the initial water deficit and the velocity travel for each flood event assimilating the first available discharge measurements at the catchment outlet. The advantages of the BLUE algorithm are its low computational cost and its convenient implementation, especially in the context of the calibration of a reduced number of parameters. The assimilation algorithm was applied on two Mediterranean catchment areas of different size and dynamics: Gardon d'Anduze and Lez. The Lez catchment, of 114 km2 drainage area, is located upstream Montpellier. It is a karstic catchment mainly affected by floods in autumn during intense rainstorms with short Lag-times and high discharge peaks (up to 480 m3.s-1 in September 2005). The Gardon d'Anduze catchment, mostly granite and schistose, of 545 km2 drainage area, lies over the departements of Lozère and Gard. It is often affected by flash and devasting floods (up to 3000 m3.s-1 in September 2002). The discharge observations at the beginning of the flood event are assimilated so that the BLUE algorithm provides optimal values for the initial water deficit and the velocity travel before the flood peak. These optimal values are used for a new simulation of the event in forecast mode (under the assumption of perfect rain-fall). On both catchments, it was shown over a significant number of flood events, that the data assimilation procedure improves the flood peak forecast. The improvement is globally more important for the Gardon d'Anduze catchment where the flood events are stronger. The peak can be forecasted up to 36 hours head of time assimilating very few observations (up to 4) during the rise of the water level. For multiple peaks events, the assimilation of the observations from the first peak leads to a significant improvement of the second peak simulation. It was also shown that the flood rise is often faster in reality than it is represented by the model. In this case and when the flood peak is under estimated in the simulation, the use of the first observations can be misleading for the data assimilation algorithm. The careful estimation of the observation and background error variances enabled the satisfying use of the data assimilation in these complex cases even though it does not allow the model error correction.

Predicting Fog in the Nocturnal Boundary Layer

NASA Astrophysics Data System (ADS)

Izett, Jonathan; van de Wiel, Bas; Baas, Peter; van der Linden, Steven; van Hooft, Antoon; Bosveld, Fred

2017-04-01

Fog is a global phenomenon that presents a hazard to navigation and human safety, resulting in significant economic impacts for air and shipping industries as well as causing numerous road traffic accidents. Accurate prediction of fog events, however, remains elusive both in terms of timing and occurrence itself. Statistical methods based on set threshold criteria for key variables such as wind speed have been developed, but high rates of correct prediction of fog events still lead to similarly high "false alarms" when the conditions appear favourable, but no fog forms. Using data from the CESAR meteorological observatory in the Netherlands, we analyze specific cases and perform statistical analyses of event climatology, in order to identify the necessary conditions for correct prediction of fog. We also identify potential "missing ingredients" in current analysis that could help to reduce the number of false alarms. New variables considered include the indicators of boundary layer stability, as well as the presence of aerosols conducive to droplet formation. The poster presents initial findings of new research as well as plans for continued research.

The 2012 July 23 Backside Eruption: An Extreme Energetic Particle Event?

NASA Technical Reports Server (NTRS)

Gopalswamy, N.; Yashiro, S.; Thakur, N.; Makela, P.; Xie, H.; Akiyama, S.

2016-01-01

The backside coronal mass ejection (CME) of 2012 July 23 had a short Sun-to-Earth shock transit time (18.5 hr).The associated solar energetic particle (SEP) event had a greater than 10 MeV proton flux peaking at approximately 5000 pfu, and the energetic storm particle event was an order of magnitude larger, making it the most intense event in the space era at these energies. By a detailed analysis of the CME, shock, and SEP characteristics, we find that the July 23 event is consistent with a high-energy SEP event (accelerating particles to giga-electron volt energies). The times of maximum and fluence spectra in the range 10100 MeV were very hard, similar to those of ground-level enhancement (GLE) events. We found a hierarchical relationship between the CME initial speeds and the fluence spectral indices: CMEs with low initial speeds had SEP events with the softest spectra, while those with the highest initial speeds had SEP events with the hardest spectra. CMEs attaining intermediate speeds result in moderately hard spectra. The July 23 event was in the group of hard-spectrum events. During the July 23 event, the shock speed greater than (2000 km s(exp -1), the initial acceleration (approximately 1.70 km s(exp -2), and the shock-formation height (approximately 1.5 solar radii)were all typical of GLE events. The associated type II burst had emission components from meter to kilometer wavelengths, suggesting a strong shock. These observations confirm that the 2012 July 23 event is likely to be an extreme event in terms of the energetic particles it accelerated.

THE 2012 JULY 23 BACKSIDE ERUPTION: AN EXTREME ENERGETIC PARTICLE EVENT?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gopalswamy, N.; Yashiro, S.; Thakur, N.

The backside coronal mass ejection (CME) of 2012 July 23 had a short Sun-to-Earth shock transit time (18.5 hr). The associated solar energetic particle (SEP) event had a >10 MeV proton flux peaking at ∼5000 pfu, and the energetic storm particle event was an order of magnitude larger, making it the most intense event in the space era at these energies. By a detailed analysis of the CME, shock, and SEP characteristics, we find that the July 23 event is consistent with a high-energy SEP event (accelerating particles to gigaelectronvolt energies). The times of maximum and fluence spectra in the rangemore » 10–100 MeV were very hard, similar to those of ground-level enhancement (GLE) events. We found a hierarchical relationship between the CME initial speeds and the fluence spectral indices: CMEs with low initial speeds had SEP events with the softest spectra, while those with the highest initial speeds had SEP events with the hardest spectra. CMEs attaining intermediate speeds result in moderately hard spectra. The July 23 event was in the group of hard-spectrum events. During the July 23 event, the shock speed (>2000 km s{sup −1}), the initial acceleration (∼1.70 km s{sup −2}), and the shock-formation height (∼1.5 solar radii) were all typical of GLE events. The associated type II burst had emission components from meter to kilometer wavelengths, suggesting a strong shock. These observations confirm that the 2012 July 23 event is likely to be an extreme event in terms of the energetic particles it accelerated.« less

Interactive effects of childhood maltreatment and recent stressful life events on alcohol consumption in adulthood.

PubMed

Young-Wolff, Kelly C; Kendler, Kenneth S; Prescott, Carol A

2012-07-01

Childhood maltreatment is associated with early alcohol use initiation, alcohol-related problem behaviors, and alcohol use disorders in adulthood. Heavy drinking risk among individuals exposed to childhood maltreatment could be partly attributable to stress sensitization, whereby early adversity leads to psychobiological changes that heighten sensitivity to subsequent stressors and increase risk for stress-related drinking. We addressed this issue by examining whether the association between past-year stressful life events and past-year drinking density, a weighted quantity-frequency measure of alcohol consumption, was stronger among adults exposed to childhood maltreatment. Drinking density, stressful life events, and child maltreatment were assessed using structured clinical interviews in a sample of 4,038 male and female participants ages 20-58 years from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. Stress sensitization was examined using hierarchical multiple regression analyses to test whether stressful events moderated the association between maltreatment and drinking density. Analyses were stratified by sex and whether the impact was different for independent stressful events or dependent stressful events as related to a participant's actions. Independent stressful events were associated with heavier drinking density among women exposed to maltreatment. In contrast, drinking density was roughly the same across independent stressful life events exposure among women not exposed to maltreatment. There was little evidence for Maltreatment × Independent Stressor interactions in men or Maltreatment × Dependent Stressor interactions in either gender. Early maltreatment may have direct effects on vulnerability to stress-related drinking among women, particularly in association with stressors that are out of one's control.

Modeling a molecular initiating event to population effects: A case study of aromatase inhibition in fathead minnows

EPA Science Inventory

An adverse outcome pathway (AOP) conceptually links a molecular initiating event with measureable key events at higher levels of biological organization that ultimately result in an adverse outcome. Development of an AOP requires experimental data and scientific expertise to ide...

Population age and initial density in a patchy environment affect the occurrence of abrupt transitions in a birth-and-death model of Taylor's law

USGS Publications Warehouse

Jiang, Jiang; DeAngelis, Donald L.; Zhang, B.; Cohen, J.E.

2014-01-01

Taylor's power law describes an empirical relationship between the mean and variance of population densities in field data, in which the variance varies as a power, b, of the mean. Most studies report values of b varying between 1 and 2. However, Cohen (2014a) showed recently that smooth changes in environmental conditions in a model can lead to an abrupt, infinite change in b. To understand what factors can influence the occurrence of an abrupt change in b, we used both mathematical analysis and Monte Carlo samples from a model in which populations of the same species settled on patches, and each population followed independently a stochastic linear birth-and-death process. We investigated how the power relationship responds to a smooth change of population growth rate, under different sampling strategies, initial population density, and population age. We showed analytically that, if the initial populations differ only in density, and samples are taken from all patches after the same time period following a major invasion event, Taylor's law holds with exponent b=1, regardless of the population growth rate. If samples are taken at different times from patches that have the same initial population densities, we calculate an abrupt shift of b, as predicted by Cohen (2014a). The loss of linearity between log variance and log mean is a leading indicator of the abrupt shift. If both initial population densities and population ages vary among patches, estimates of b lie between 1 and 2, as in most empirical studies. But the value of b declines to ~1 as the system approaches a critical point. Our results can inform empirical studies that might be designed to demonstrate an abrupt shift in Taylor's law.

Efficient dispersal and substrate acquisition traits in a marine invasive species via transient chimerism and colony mobility

PubMed Central

Fidler, Andrew E.; Bacq-Labreuil, Aurelie; Rachmilovitz, Elad

2018-01-01

Over the past three decades the colonial ascidian Didemnum vexillum has been expanding its global range, significantly impacting marine habitats and aquaculture facilities. What biological features make D. vexillum so highly invasive? Here, we show that juxtaposed allogeneic D. vexillum colony fragments (‘ramets’) may, initially, form chimeric entities. Subsequently, zooids of the differing genotypes within such chimeras coordinately retreat away from fusion zones. A few days following such post-fusion retreat movements there is further ramet fission and the formation of zooid-depauperate tunic zones. Using polymorphic microsatellite loci to distinguish between genotypes, we found that they were sectorial at the fusion zones and the subsequent ramet movements resulted in further spatial separation of the paired-genotypes indicating that the fusion events observed did not lead to formation of long-term, stable chimeras. Thus, movements of D. vexillum colony ramets from initial fusion zones lead to progressive segregation of genotypes probably minimizing potential somatic/germ-cell competition/parasitism. We speculate that relatively fast (≤10 mm/day) movement of D. vexillum colonies on substrates along with frequent, and perhaps unrestrained, transient allogeneic fusions play significant roles in this species’ striking invasiveness and capacity to colonize new substrates.

Surface Acoustic Wave (SAW) Resonators for Monitoring Conditioning Film Formation

PubMed Central

Hohmann, Siegfried; Kögel, Svea; Brunner, Yvonne; Schmieg, Barbara; Ewald, Christina; Kirschhöfer, Frank; Brenner-Weiß, Gerald; Länge, Kerstin

2015-01-01

We propose surface acoustic wave (SAW) resonators as a complementary tool for conditioning film monitoring. Conditioning films are formed by adsorption of inorganic and organic substances on a substrate the moment this substrate comes into contact with a liquid phase. In the case of implant insertion, for instance, initial protein adsorption is required to start wound healing, but it will also trigger immune reactions leading to inflammatory responses. The control of the initial protein adsorption would allow to promote the healing process and to suppress adverse immune reactions. Methods to investigate these adsorption processes are available, but it remains difficult to translate measurement results into actual protein binding events. Biosensor transducers allow user-friendly investigation of protein adsorption on different surfaces. The combination of several transduction principles leads to complementary results, allowing a more comprehensive characterization of the adsorbing layer. We introduce SAW resonators as a novel complementary tool for time-resolved conditioning film monitoring. SAW resonators were coated with polymers. The adsorption of the plasma proteins human serum albumin (HSA) and fibrinogen onto the polymer-coated surfaces were monitored. Frequency results were compared with quartz crystal microbalance (QCM) sensor measurements, which confirmed the suitability of the SAW resonators for this application. PMID:26007735

Evaluation of Event Physical Activity Engagement at an Open Streets Initiative Within a Texas-Mexico Border Town.

PubMed

Salazar-Collier, Cindy Lynn; Reininger, Belinda; Gowen, Rose; Rodriguez, Arturo; Wilkinson, Anna

2018-05-09

Open streets initiatives provide an opportunity to engage in physical activity (PA) freely by temporarily closing streets to motorized traffic. Route counting estimation and event intercept surveys (n = 682) were conducted across 4 CycloBia events in Brownsville, TX, in 2015 to determine sociodemographics, PA engagement at the event, event awareness, and past CycloBia attendance. Cycling was the most commonly observed activity along the route (73.6%) followed by walking (22.9%). Attendees self-reported a median of 120 minutes in PA with 17.3% of attendees meeting recommended weekly PA guidelines at the event. Significant predictors of meeting PA guidelines via event PA engagement were past event attendance, sex, age, and Hispanic ethnicity. Findings suggest that CycloBia reached a large, low-income, predominantly Hispanic population and may be effective in promoting PA. Results help understand the effect of an open streets initiative on attendees living in a midsize, border city.

Air-temperature variations and ENSO effects in Indonesia, the Philippines and El Salvador. ENSO patterns and changes from 1866-1993

NASA Astrophysics Data System (ADS)

Harger, J. R. E.

The major features in development of the "El Nino-Southern Oscillation" (ENSO) involve oscillation of the Pacific ocean-atmosphere in an essentially unpredictable (chaotic) fashion. The system moves between extremes of the so-called "warm events" lasting one or two years and involving movement of warm sea water from the western Pacific along the equator to impact on the west coast of the American continent and "cold-events" associated with easterly trade-wind-induced flows of colder water from the eastern Pacific towards the west. Historical data indicate that ENSO years as experienced by the Island of Java are either much warmer than non-ENSO years or only slightly, if at all, warmer than normal (non-ENSO) years. Hot-dry years within the ENSO warm event cycle are almost always followed by cooler wet years and vice versa. This pattern also extends to include the year immediately following the terminal year of an ENSO warm event set. The initial year of an ENSO warm event set may be either hot with a long dry season or relatively cool (nearer to the temperature of a non-ENSO year) and having a short dry season. In recent years, since 1950, of the 9 ENSO warm events, the initial year tends to have been hot and dry for 6 (1951, 1957, 1963, 1972, 1982, 1991) and neutral or cool and wet for 3 (1968, 1976, 1986). An area of 88,000 ha burned in 1991 (Jakarta Post 30 November 1991) largely in Kalimantan in association with the 1991-1992 ENSO event, an extensive pall of smoke developed over Kalimantan, Singapore and Malaysia during September-October of 1991. Surface vegetation-based fires continued to burn in East Kalimantan as of 29 April 1992 and extended into the 1992 dry season, in response to the ENSO conditions carrying forward from 1991. The increasing annual trend in air-temperature exhibited by the mean monthly values over the period 1866-1993, for the Jakarta and the Semarang data taken together is 1.64°C (0.0132°C per year from 25.771 to 27.409°C). The major industrial development in infrastructure for Jakarta has been significant only since 1980 or so and was not apparent before 1970 when the city had the aspect of an extended village with few large buildings (greater than 3-4 stories) and no extensive highways. The 1.65° difference between 1866 and 1991 can presumably by partitioned into: (1) urban heat-island effect, (2) effect of deforestation, (3) effect of secular micro-climate shift, (4) influence of general global warming with particular reference to the tropics. When the blocks of non-ENSO years in themselves are considered, the deviations from the secular trend for warmest month mean temperatures in successive years are correlated with that of the next immediate year deviation so that either continual warming or cooling appears to take place from the termination of one ENSO to the initiation of the next. When the deviations around the secular trend shown by the warmest month average temperatures are summed for the inter-ENSO intervals (the separate non-ENSO years) the resultant "heat-loading" index is positively correlated with the following (initial) ENSO warmest month deviation from the overall ENSO warmest month secular trend. This provides an immediate predictive mechanism for the likely strength of an ENSO, in terms of the dry season impact to the Island of Java, should one occur in the next year to break a non-ENSO sequence. The length of the build-up and the build-up achieved seems not to be related. The relationship does not in itself however, predict the occurrence of the "next" ENSO. The data show that a consistent structure underlies ENSO events for the last century and a quarter. However, as a process monitored by mean monthly air-temperature measurements at Jakarta-Semarang, the system is changing in character with time in association with an overall atmospheric temperature increase in a way that involves increased intra-annual temperature fluctuations. In general ENSO years are associated with higher temperatures than non-ENSO years, with a significant negative correlation between subsequent years which are thereafter systematically cooler. This may be because the ENSO event actively mixes excess heat energy into the ocean-sink to an extent that is in direct proportion to the outstanding positive temperature deviation. A weak ENSO, preceded by a relatively modest temperature build-up in the lead-up non-ENSO years, then results in limited mixing which leads to a relatively warm subsequent year while a strong event leads to extensive mixing and so generally results in a following very much cooler year. Atmospheric temperature build-up possibly associated with the greenhouse effect may be coupled to an increasingly wider temperature swing in west and central Java associated with the warm pool influence but anchored by the ocean-sink.

Treatment Patterns and Early Outcomes of ALK-Positive Non-Small Cell Lung Cancer Patients Receiving Ceritinib: A Chart Review Study.

PubMed

Bendaly, Edmond; Dalal, Anand A; Culver, Kenneth; Galebach, Philip; Bocharova, Iryna; Foster, Rebekah; Sasane, Medha; Macalalad, Alexander R; Guérin, Annie

2017-05-01

This study aimed to provide the first real-world description of the characteristics, treatments, dosing patterns, and early outcomes of patients with ALK-positive non-small cell lung cancer (NSCLC) who received ceritinib in US clinical practice. US oncologists provided data from medical charts of adult patients diagnosed with locally advanced or metastatic ALK-positive NSCLC who received ceritinib following crizotinib. Patient characteristics, treatment patterns, ceritinib dosing, early outcomes, and occurrence of gastrointestinal adverse events (AEs) by dose and instructions on food intake were assessed, and Kaplan-Meier analysis was used to describe clinician-defined progression-free survival (PFS) on ceritinib. Medical charts of 58 ALK-positive NSCLC patients treated with ceritinib were reviewed (median age 63 years; 41% male; 21% with prior chemotherapy experience). At ceritinib initiation, 44 patients had multiple distant metastases, most commonly in the liver (60%), bone (53%), and brain (38%). Initial ceritinib dose varied: 71% received 750 mg, 19% 600 mg, and 10% 450 mg. Although median follow-up after ceritinib initiation was short (3.8 months), most patients achieved either a complete or partial response (69%) on ceritinib, regardless of metastatic sites present at initiation or initial dose. Median PFS on ceritinib was 12.9 months. 17% of patients had a gastrointestinal AE reported during follow-up. The majority of events occurred in patients instructed to fast; no patients instructed to take a lower dose of ceritinib with food reported gastrointestinal AEs. These early findings of ceritinib use in clinical practice suggest that ceritinib is effective at treating crizotinib-experienced ALK-positive NSCLC patients, regardless of metastatic sites or initial dose, and dosing ceritinib with food may lead to fewer gastrointestinal AEs. Future studies with larger sample size and longer follow-up are warranted, including an ongoing randomized trial to assess the gastrointestinal tolerability of ceritinib 450 and 600 mg with low-fat meals. Novartis Pharmaceutical Corporation.

Long period seismic signals observed before the Caldera formation during the 2000 Miyake- jima volcanic activity

NASA Astrophysics Data System (ADS)

Ohminato, T.; Kobayashi, T.; Ida, Y.; Fujita, E.

2006-12-01

During the 2000 Miyake-jima volcanic activity started on 26 June 2000, an intense earthquake swarm occurred initially beneath the southwest flank near the summit and gradually migrated west of the island. A volcanic earthquake activity in the island was reactivated beneath the summit, leading to a summit eruption with a significant summit subsidence on 8 July. We detected small but numerous number of long period (LP) seismic signals during these activities. Most of them include both 0.2 and 0.4 Hz components suggesting an existence of a harmonic oscillator. Some of them have dominant frequency peak at 0.2Hz (LP1), while others have one at 0.4 Hz (LP2). At the beginning of each waveform of both LP1 and LP2, an impulsive signal with a pulse-width of about 2 s is clearly identified. The major axis of the particle motion for the initial impulsive signal is almost horizontal suggesting a shallow source beneath the summit, while the inclined particle motion for the latter phase suggests deeper source beneath the island. For both LP1 and LP2, we can identify a clear positive correlation between the amplitude of the initial pulse and that of the latter phase. We conducted waveform inversions for the LP events assuming a point source and determined the locations and mechanisms simultaneously. We assumed three types of source mechanisms; three single forces, six moment tensor components, and a combination of moment tensor and single forces. We used AIC to decide the optimal solutions. Firstly, we applied the method to the entire waveform including both the initial pulse and the latter phase. The source type with a combination of moment tensor and single force components yields the minimum values of the AIC for both LP events. However, the spatial distribution of the residual errors tends to have two local minima. Considering the error distribution and the characteristic particle motions, it is likely that the source of the LP event consists of two different parts. We thus divided the LP events into two parts; the initial and the latter phases, and applied the same waveform inversion procedure separately for each part of the waveform. The inversion results show that the initial impulsive phase and the latter oscillatory phase are well explained by a nearly horizontal single force and a moment solution, respectively. The single force solutions of the initial pulse are positioned at the depth of about 2 km beneath the summit. The single force initially oriented to the north, and then to the south. On the other hand, the sources of the moment solutions are significantly deeper than the single force solutions. The hypocenter of the later phase of LP1 is located at the depth of 5.5 km in the southern region of the island, while that for the LP2 event is at 5.1 km beneath the summit. The horizontal oscillations are relatively dominant for both the LP1 and LP2 events. Although the two sources are separated each other by several kilometers, the positive correlation between the amplitudes of the initial pulse and the latter phase strongly suggests that the shallow sources trigger the deeper sources. The source time histories of the 6 moment tensor components of the latter portion of the LP1 and LP2 are not in phase. This makes it difficult to extract information on source geometry using the amplitude ratio among moment tensor components in a traditional manner. It may suggest that the source is composed of two independent sources whose oscillations are out of phase.

Preserve America Event ToolKit

Science.gov Websites

inception in 2003, Preserve America has become an important, multi-faceted, interagency initiative that to help organize those local events. Detailed information about the initiative is at

Preventing Harm in the ICU-Building a Culture of Safety and Engaging Patients and Families.

PubMed

Thornton, Kevin C; Schwarz, Jennifer J; Gross, A Kendall; Anderson, Wendy G; Liu, Kathleen D; Romig, Mark C; Schell-Chaple, Hildy; Pronovost, Peter J; Sapirstein, Adam; Gropper, Michael A; Lipshutz, Angela K M

2017-09-01

Preventing harm remains a persistent challenge in the ICU despite evidence-based practices known to reduce the prevalence of adverse events. This review seeks to describe the critical role of safety culture and patient and family engagement in successful quality improvement initiatives in the ICU. We review the evidence supporting the impact of safety culture and provide practical guidance for those wishing to implement initiatives aimed at improving safety culture and more effectively integrate patients and families in such efforts. Literature review using PubMed including evaluation of key studies assessing large-scale quality improvement efforts in the ICU, impact of safety culture on patient outcomes, methodologies for quality improvement commonly used in healthcare, and patient and family engagement. Print and web-based resources from leading patient safety organizations were also searched. Our group completed a review of original studies, review articles, book chapters, and recommendations from leading patient safety organizations. Our group determined by consensus which resources would best inform this review. A strong safety culture is associated with reduced adverse events, lower mortality rates, and lower costs. Quality improvement efforts have been shown to be more effective and sustainable when paired with a strong safety culture. Different methodologies exist for quality improvement in the ICU; a thoughtful approach to implementation that engages frontline providers and administrative leadership is essential for success. Efforts to substantively include patients and families in the processes of quality improvement work in the ICU should be expanded. Efforts to establish a culture of safety and meaningfully engage patients and families should form the foundation for all safety interventions in the ICU. This review describes an approach that integrates components of several proven quality improvement methodologies to enhance safety culture in the ICU and highlights opportunities to include patients and families.

Surgically-Induced Neuropathic Pain (SNPP): Understanding the Perioperative Process

PubMed Central

Borsook, David; Kussman, Barry D.; George, Edward; Becerra, Lino R.; Burke, Dennis W.

2012-01-01

Objective Nerve damage takes place during surgery. As a consequence, significant numbers (10–40%) of patients experience chronic neuropathic pain termed surgically induced neuropathic pain (SNPP). Background The initiating surgery and nerve damage set off a cascade of events that includes both pain and an inflammatory response, resulting in ‘peripheral’ and ‘central sensitization’, with the latter resulting from repeated barrages of neural activity from nociceptors. In affected patients these initial events produce chemical, structural and functional changes in the peripheral (PNS) and central nervous (CNS) systems. The maladaptive changes in damaged nerves lead to peripheral manifestations of the neuropathic state – allodynia, sensory loss, shooting pains etc., that can manifest long after the effects of the surgical injury have resolved. The CNS manifestations that occur are termed ‘centralization of pain’ and affect sensory, emotional and other (e.g., cognitive) systems as well as contributing to some of the manifestations of the chronic pain syndrome (e.g., depression). Conclusions Currently there are no objective measures of pain in the peri-operative period. As such intermittent pain or continuous may take place during and after surgery. New technologies including direct measures of specific brain function of nociception and new insights into preoperative evaluation of patients including genetic predisposition appear to provide initial opportunities for decreasing the burden of SNPP until treatments with high efficacy and low side effects that either prevent or treat pain are discovered. PMID:23059501

Constraining the rate of oceanic deoxygenation leading up to a Cretaceous Oceanic Anoxic Event (OAE-2: ~94 Ma)

PubMed Central

Ostrander, Chadlin M.; Owens, Jeremy D.; Nielsen, Sune G.

2017-01-01

The rates of marine deoxygenation leading to Cretaceous Oceanic Anoxic Events are poorly recognized and constrained. If increases in primary productivity are the primary driver of these episodes, progressive oxygen loss from global waters should predate enhanced carbon burial in underlying sediments—the diagnostic Oceanic Anoxic Event relic. Thallium isotope analysis of organic-rich black shales from Demerara Rise across Oceanic Anoxic Event 2 reveals evidence of expanded sediment-water interface deoxygenation ~43 ± 11 thousand years before the globally recognized carbon cycle perturbation. This evidence for rapid oxygen loss leading to an extreme ancient climatic event has timely implications for the modern ocean, which is already experiencing large-scale deoxygenation. PMID:28808684

Fabry nephropathy: a review - how can we optimize the management of Fabry nephropathy?

PubMed

Waldek, Stephen; Feriozzi, Sandro

2014-05-06

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment.

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

PubMed Central

2014-01-01

Fabry disease is a rare, X-linked, lysosomal storage disease caused by mutations in the gene encoding the enzyme alpha-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, epithelial cells and the tubular cells of the distal tubule and loop of Henle contribute to the renal symptoms of Fabry disease, which manifest as proteinuria and reduced glomerular filtration rate leading to chronic kidney disease and progression to end-stage renal disease. Early diagnosis and timely initiation of treatment of Fabry renal disease is an important facet of disease management. Initiating treatment with enzyme replacement therapy (ERT; agalsidase alfa, Replagal®, Shire; agalsidase beta, Fabrazyme®, Genzyme) as part of a comprehensive strategy to prevent complications of the disease, may be beneficial in stabilizing renal function or slowing its decline. Early initiation of ERT may also be more effective than initiating therapy in patients with more advanced disease. Several strategies are required to complement the use of ERT and treat the myriad of associated symptoms and organ involvements. In particular, patients with renal Fabry disease are at risk of cardiovascular events, such as high blood pressure, cardiac arrhythmias and stroke. This review discusses the management of renal involvement in Fabry disease, including diagnosis, treatments, and follow-up, and explores recent advances in the use of biomarkers to assist with diagnosis, monitoring disease progression and response to treatment. PMID:24886109

Disruption of Transcriptional Coactivator Sub1 Leads to Genome-Wide Re-distribution of Clustered Mutations Induced by APOBEC in Active Yeast Genes

PubMed Central

Dhar, Alok; Polev, Dmitrii E.; Masharsky, Alexey E.; Rogozin, Igor B.; Pavlov, Youri I.

2015-01-01

Mutations in genomes of species are frequently distributed non-randomly, resulting in mutation clusters, including recently discovered kataegis in tumors. DNA editing deaminases play the prominent role in the etiology of these mutations. To gain insight into the enigmatic mechanisms of localized hypermutagenesis that lead to cluster formation, we analyzed the mutational single nucleotide variations (SNV) data obtained by whole-genome sequencing of drug-resistant mutants induced in yeast diploids by AID/APOBEC deaminase and base analog 6-HAP. Deaminase from sea lamprey, PmCDA1, induced robust clusters, while 6-HAP induced a few weak ones. We found that PmCDA1, AID, and APOBEC1 deaminases preferentially mutate the beginning of the actively transcribed genes. Inactivation of transcription initiation factor Sub1 strongly reduced deaminase-induced can1 mutation frequency, but, surprisingly, did not decrease the total SNV load in genomes. However, the SNVs in the genomes of the sub1 clones were re-distributed, and the effect of mutation clustering in the regions of transcription initiation was even more pronounced. At the same time, the mutation density in the protein-coding regions was reduced, resulting in the decrease of phenotypically detected mutants. We propose that the induction of clustered mutations by deaminases involves: a) the exposure of ssDNA strands during transcription and loss of protection of ssDNA due to the depletion of ssDNA-binding proteins, such as Sub1, and b) attainment of conditions favorable for APOBEC action in subpopulation of cells, leading to enzymatic deamination within the currently expressed genes. This model is applicable to both the initial and the later stages of oncogenic transformation and explains variations in the distribution of mutations and kataegis events in different tumor cells. PMID:25941824

Defectors Can Create Conditions That Rescue Cooperation

PubMed Central

Waite, Adam James; Cannistra, Caroline; Shou, Wenying

2015-01-01

Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators) will grow more than those in defector-dominated locations (which are most likely defectors), cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local population size. We predict that in a structured population, small population sizes precipitated by defectors provide a “built-in” mechanism for the persistence of cooperation. PMID:26690946

Data-driven clustering of rain events: microphysics information derived from macro-scale observations

NASA Astrophysics Data System (ADS)

Djallel Dilmi, Mohamed; Mallet, Cécile; Barthes, Laurent; Chazottes, Aymeric

2017-04-01

Rain time series records are generally studied using rainfall rate or accumulation parameters, which are estimated for a fixed duration (typically 1 min, 1 h or 1 day). In this study we use the concept of rain events. The aim of the first part of this paper is to establish a parsimonious characterization of rain events, using a minimal set of variables selected among those normally used for the characterization of these events. A methodology is proposed, based on the combined use of a genetic algorithm (GA) and self-organizing maps (SOMs). It can be advantageous to use an SOM, since it allows a high-dimensional data space to be mapped onto a two-dimensional space while preserving, in an unsupervised manner, most of the information contained in the initial space topology. The 2-D maps obtained in this way allow the relationships between variables to be determined and redundant variables to be removed, thus leading to a minimal subset of variables. We verify that such 2-D maps make it possible to determine the characteristics of all events, on the basis of only five features (the event duration, the peak rain rate, the rain event depth, the standard deviation of the rain rate event and the absolute rain rate variation of the order of 0.5). From this minimal subset of variables, hierarchical cluster analyses were carried out. We show that clustering into two classes allows the conventional convective and stratiform classes to be determined, whereas classification into five classes allows this convective-stratiform classification to be further refined. Finally, our study made it possible to reveal the presence of some specific relationships between these five classes and the microphysics of their associated rain events.

Tropical river suspended sediment and solute dynamics in storms during an extreme drought

USGS Publications Warehouse

Clark, Kathryn E.; Shanley, James B.; Scholl, Martha A.; Perdrial, Nicolas; Perdrial, Julia N.; Plante, Alain F.; McDowell, William H.

2017-01-01

Droughts, which can strongly affect both hydrologic and biogeochemical systems, are projected to become more prevalent in the tropics in the future. We assessed the effects of an extreme drought during 2015 on stream water composition in the Luquillo Mountains of Puerto Rico. We demonstrated that drought base flow in the months leading up to the study was sourced from trade-wind orographic rainfall, suggesting a resistance to the effects of an otherwise extreme drought. In two catchments (Mameyes and Icacos), we sampled a series of four rewetting events that partially alleviated the drought. We collected and analyzed dissolved constituents (major cations and anions, organic carbon, and nitrogen) and suspended sediment (inorganic and organic matter (particulate organic carbon and particulate nitrogen)). The rivers appeared to be resistant to extreme drought, recovering quickly upon rewetting, as (1) the concentration-discharge (C-Q) relationships deviated little from the long-term patterns; (2) “new water” dominated streamflow during the latter events; (3) suspended sediment sources had accumulated in the channel during the drought flushed out during the initial events; and (4) the severity of the drought, as measured by the US drought monitor, was reduced dramatically after the rewetting events. Through this interdisciplinary study, we were able to investigate the impact of extreme drought through rewetting events on the river biogeochemistry.

Effects of dissolved organic matter leaching from macrophyte litter on black water events in shallow lakes.

PubMed

He, Yuhong; Song, Na; Jiang, He-Long

2018-04-01

In recent years, the black water phenomenon has become an environmental event in eutrophic shallow lakes in China, leading to deterioration of lake ecosystems and potable water crises. Decomposition of macrophyte debris has been verified as a key inducement for black water events. In this study, the effects of the decomposition of dissolved organic matter (Kottelat et al., WASP 187:343-351, 2008) derived from macrophyte leachate on the occurrence of black water events are investigated to clarify the detailed mechanisms involved. Results show that dissolved organic matter (DOM) is composed of a trace of chromophoric DOM and mostly non-chromophoric dissolved organic matter (CDOM). DOM decomposition is accompanied by varied concentration of CDOM components, generation of organic particles, and increased microbial concentrations. These processes increase water chroma only during initial 48 h, so the intensified water color cannot be maintained by DOM decomposition alone. During DOM decomposition, microorganisms first consume non-CDOM, increasing the relative CDOM concentration and turning the water color to black (or brown). Simultaneously, tryptophan and aromatic proteins, which are major ingredients of CDOM, enhance UV light absorption, further aggravating the macroscopic phenomenon of black color. Our results show that DOM leached from decayed macrophytes promotes or even triggers the occurrence of black water events and should be taken more seriously in the future.

High fat programming of beta cell compensation, exhaustion, death and dysfunction.

PubMed

Cerf, Marlon E

2015-03-01

Programming refers to events during critical developmental windows that shape progeny health outcomes. Fetal programming refers to the effects of intrauterine (in utero) events. Lactational programming refers to the effects of events during suckling (weaning). Developmental programming refers to the effects of events during both fetal and lactational life. Postnatal programming refers to the effects of events either from birth (lactational life) to adolescence or from weaning (end of lactation) to adolescence. Islets are most plastic during the early life course; hence programming during fetal and lactational life is most potent. High fat (HF) programming is the maintenance on a HF diet (HFD) during critical developmental life stages that alters progeny metabolism and physiology. HF programming induces variable diabetogenic phenotypes dependent on the timing and duration of the dietary insult. Maternal obesity reinforces HF programming effects in progeny. HF programming, through acute hyperglycemia, initiates beta cell compensation. However, HF programming eventually leads to chronic hyperglycemia that triggers beta cell exhaustion, death and dysfunction. In HF programming, beta cell dysfunction often co-presents with insulin resistance. Balanced, healthy nutrition during developmental windows is critical for preserving beta cell structure and function. Thus early positive nutritional interventions that coincide with the development of beta cells may reduce the overwhelming burden of diabetes and metabolic disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Particle size distribution variance in untreated urban runoff and its implication on treatment selection.

PubMed

Charters, Frances J; Cochrane, Thomas A; O'Sullivan, Aisling D

2015-11-15

Understanding the particle size distribution (PSD) of sediment in urban runoff assists in the selection of appropriate treatment systems for sediment removal as systems vary in their ability to remove sediment across different particle size fractions. Variation in PSD in runoff from individual urban surfaces both during and across multiple rain events is not well understood and it may lead to performance uncertainty in treatment systems. Runoff PSDs in international literature were compiled to provide a comparative summary of PSDs from different urban surfaces. To further assess both intra-event and inter-event PSD variation, untreated runoff was collected from road, concrete roof, copper roof, and galvanized roof surfaces within an urban catchment exposed to the same rainfall conditions and analysed for PSD and total suspended solids (TSS). Road runoff had the highest TSS concentrations, while copper roofs had high initial TSS that reduced to very low levels under steady state conditions. Despite variation in TSS concentrations, the median particle diameter of the TSS was comparable across the surfaces. Intra-event variation was generally not significant, but substantial inter-event variation was observed, particularly for coarser road and concrete roof surfaces. PSD variation for each surface contributed to a wide range in predicted treatment performance and suggests that short-retention treatment devices carry a high performance risk of not being able to achieve adequate TSS removal across all rain events. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reduction in Total Cardiovascular Events With Ezetimibe/Simvastatin Post-Acute Coronary Syndrome: The IMPROVE-IT Trial.

PubMed

Murphy, Sabina A; Cannon, Christopher P; Blazing, Michael A; Giugliano, Robert P; White, Jennifer A; Lokhnygina, Yuliya; Reist, Craig; Im, KyungAh; Bohula, Erin A; Isaza, Daniel; Lopez-Sendon, Jose; Dellborg, Mikael; Kher, Uma; Tershakovec, Andrew M; Braunwald, Eugene

2016-02-02

Intensive low-density lipoprotein cholesterol therapy with ezetimibe/simvastatin in IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial) significantly reduced the first primary endpoint (PEP) in patients post-acute coronary syndrome (ACS) compared to placebo/simvastatin. This analysis tested the hypothesis that total events, including those beyond the first event, would also be reduced with ezetimibe/simvastatin therapy. All PEP events (cardiovascular [CV] death, myocardial infarction [MI], stroke, unstable angina [UA] leading to hospitalization, coronary revascularization ≥30 days post-randomization) during a median 6-year follow-up were analyzed in patients randomized to receive ezetimibe/simvastatin or placebo/simvastatin in IMPROVE-IT. Negative binomial regression was used for the primary analysis. Among 18,144 patients, there were 9,545 total PEP events (56% were first events and 44% subsequent events). Total PEP events were significantly reduced by 9% with ezetimibe/simvastatin vs placebo/simvastatin (incidence-rate ratio [RR]: 0.91; 95% confidence interval [CI]: 0.85 to 0.97; p = 0.007), as were the 3 pre-specified secondary composite endpoints and the exploratory composite endpoint of CV death, MI, or stroke (RR: 0.88; 95% CI: 0.81 to 0.96; p = 0.002). The reduction in total events was driven by decreases in total nonfatal MI (RR: 0.87; 95% CI: 0.79 to 0.96; p = 0.004) and total NF stroke (RR: 0.77; 95% CI: 0.65 to 0.93; p = 0.005). Lipid-lowering therapy with ezetimibe plus simvastatin improved clinical outcomes. Reductions in total PEP events, driven by reductions in MI and stroke, more than doubled the number of events prevented compared with examining only the first event. These data support continuation of intensive combination lipid-lowering therapy after an initial CV event. (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT]; NCT00202878). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Single CA3 pyramidal cells trigger sharp waves in vitro by exciting interneurones.

PubMed

Bazelot, Michaël; Teleńczuk, Maria T; Miles, Richard

2016-05-15

The CA3 hippocampal region generates sharp waves (SPW), a population activity associated with neuronal representations. The synaptic mechanisms responsible for the generation of these events still require clarification. Using slices maintained in an interface chamber, we found that the firing of single CA3 pyramidal cells triggers SPW like events at short latencies, similar to those for the induction of firing in interneurons. Multi-electrode records from the CA3 stratum pyramidale showed that pyramidal cells triggered events consisting of putative interneuron spikes followed by field IPSPs. SPW fields consisted of a repetition of these events at intervals of 4-8 ms. Although many properties of induced and spontaneous SPWs were similar, the triggered events tended to be initiated close to the stimulated cell. These data show that the initiation of SPWs in vitro is mediated via pyramidal cell synapses that excite interneurons. They do not indicate why interneuron firing is repeated during a SPW. Sharp waves (SPWs) are a hippocampal population activity that has been linked to neuronal representations. We show that SPWs in the CA3 region of rat hippocampal slices can be triggered by the firing of single pyramidal cells. Single action potentials in almost one-third of pyramidal cells initiated SPWs at latencies of 2-5 ms with probabilities of 0.07-0.76. Initiating pyramidal cells evoked field IPSPs (fIPSPs) at similar latencies when SPWs were not initiated. Similar spatial profiles for fIPSPs and middle components of SPWs suggested that SPW fields reflect repeated fIPSPs. Multiple extracellular records showed that the initiated SPWs tended to start near the stimulated pyramidal cell, whereas spontaneous SPWs could emerge at multiple sites. Single pyramidal cells could initiate two to six field IPSPs with distinct amplitude distributions, typically preceeded by a short-duration extracellular action potential. Comparison of these initiated fields with spontaneously occurring inhibitory field motifs allowed us to identify firing in different interneurones during the spread of SPWs. Propagation away from an initiating pyramidal cell was typically associated with the recruitment of interneurones and field IPSPs that were not activated by the stimulated pyramidal cell. SPW fields initiated by single cells were less variable than spontaneous events, suggesting that more stereotyped neuronal ensembles were activated, although neither the spatial profiles of fields, nor the identities of interneurone firing were identical for initiated events. The effects of single pyramidal cell on network events are thus mediated by different sequences of interneurone firing. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Evaluating MJO Event Initiation and Decay in the Skeleton Model using an RMM-like Index

DTIC Science & Technology

2015-11-25

climatology and document 35 the occurrence of primary, continuing, and terminating MJO events in the skeleton model. The 36 overall amount of MJO...solutions in a framework consistent with observations including MJO event 104 climatology and the precursor conditions associated with the initiation and...the 112 7 model along with several applications that include a comparison to the observed MJO event 113 climatology and identification of

Kinematics of Late Cretaceous subduction initiation in the Neo-Tethys Ocean reconstructed from ophiolites of Turkey, Cyprus, and Syria

NASA Astrophysics Data System (ADS)

Maffione, Marco; van Hinsbergen, Douwe; de Gelder, Giovanni; van der Goes, Freek; Morris, Antony

2017-04-01

Formation of new subduction zones represents one of the cornerstones of plate tectonics, yet both the kinematics and geodynamics governing this process remain enigmatic. A major subduction initiation event occurred in the Late Cretaceous, within the Neo-Tethys Ocean between Gondwana and Eurasia. Supra-subduction zone (SSZ) ophiolites (i.e., emerged fragments of ancient oceanic lithosphere accreted at supra-subduction spreading centers) were generated during this subduction event, and are today distributed in the eastern Mediterranean region along three E-W trending ophiolitic belts. Current models associate these ophiolite belts to simultaneous initiation of multiple, E-W trending subduction zones at 95 Ma. Here we report paleospreading direction data obtained from paleomagnetic analysis of sheeted dyke sections from seven Neo-Tethyan ophiolites of Turkey, Cyprus, and Syria, demonstrating that these ophiolites formed at NNE-SSW striking ridges parallel to the newly formed subduction zones. This subduction system was step-shaped and composed of NNE-SSW and ESE-WNW segments. The eastern subduction segment invaded the SW Mediterranean, leading to a radial obduction pattern similar to the Banda arc. Emplacement age constraints indicate that this subduction system formed close to the Triassic passive and paleo-transform margins of the Anatolide-Tauride continental block. Because the original Triassic-Jurassic Neo-Tethyan spreading ridge must have already subducted below the Pontides before the Late Cretaceous, we infer that the Late Cretaceous Neo-Tethyan subduction system started within ancient lithosphere, along NNE-SSW oriented fracture zones and faults parallel to the E-W trending passive margins. This challenges current concepts suggesting that subduction initiation occurs along active intra-oceanic plate boundaries.

Tornado wind-loading requirements based on risk assessment techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deobald, T.L.; Coles, G.A.; Smith, G.L.

Regulations require that nuclear power plants be protected from tornado winds. If struck by a tornado, a plant must be capable of safely shutting down and removing decay heat. Probabilistic techniques are used to show that risk to the public from the US Department of Energy (DOE) SP-100 reactor is acceptable without tornado hardening parts of the secondary system. Relaxed requirements for design wind loadings will result in significant cost savings. To demonstrate an acceptable level of risk, this document examines tornado-initiated accidents. The two tornado-initiated accidents examined in detail are loss of cooling resulting in core damage and lossmore » of secondary system boundary integrity leading to sodium release. Loss of core cooling is analyzed using fault/event tree models. Loss of secondary system boundary integrity is analyzed by comparing the consequences to acceptance criteria for the release of radioactive material or alkali metal aerosol. 4 refs., 4 figs.« less

Calibration of decadal ensemble predictions

NASA Astrophysics Data System (ADS)

Pasternack, Alexander; Rust, Henning W.; Bhend, Jonas; Liniger, Mark; Grieger, Jens; Müller, Wolfgang; Ulbrich, Uwe

2017-04-01

Decadal climate predictions are of great socio-economic interest due to the corresponding planning horizons of several political and economic decisions. Due to uncertainties of weather and climate, forecasts (e.g. due to initial condition uncertainty), they are issued in a probabilistic way. One issue frequently observed for probabilistic forecasts is that they tend to be not reliable, i.e. the forecasted probabilities are not consistent with the relative frequency of the associated observed events. Thus, these kind of forecasts need to be re-calibrated. While re-calibration methods for seasonal time scales are available and frequently applied, these methods still have to be adapted for decadal time scales and its characteristic problems like climate trend and lead time dependent bias. Regarding this, we propose a method to re-calibrate decadal ensemble predictions that takes the above mentioned characteristics into account. Finally, this method will be applied and validated to decadal forecasts from the MiKlip system (Germany's initiative for decadal prediction).

Technology innovation for patients with kidney disease.

PubMed

Mitsides, Nicos; Keane, David F; Lindley, Elizabeth; Mitra, Sandip

2014-01-01

The loss of kidney function is a life-changing event leading to life-long dependence on healthcare. Around 5000 people are diagnosed with kidney failure every year. Historically, technology in renal medicine has been employed for replacement therapies. Recently, a lot of emphasis has been placed on technologies that aid early identification and prevent progression of kidney disease, while at the same time empowering affected individuals to gain control over their chronic illness. There is a shift in diversity of technology development, driven by collaborative innovation initiatives such the National Institute's for Health Research Healthcare Technology Co-operative for Devices for Dignity. This has seen the emergence of the patient as a key figure in designing technologies that are fit for purpose, while business involvement has ensured uptake and sustainability of these developments. An embodiment of this approach is the first successful Small Business Research Initiative in the field of renal medicine in the UK.

Proteome and Secretome Analysis Reveals Differential Post-transcriptional Regulation of Toll-like Receptor Responses*

PubMed Central

Koppenol-Raab, Marijke; Sjoelund, Virginie; Manes, Nathan P.; Gottschalk, Rachel A.; Dutta, Bhaskar; Benet, Zachary L.; Fraser, Iain D. C.

2017-01-01

The innate immune system is the organism's first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. PMID:28235783

Summary of events and geotechnical factors leading to decommissioning of the Strategic Petroleum Reserve (SPR) facility at Weeks Island, Louisiana

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neal, J.T.; Bauer, S.J.; Ehgartner, B.L.

1996-10-01

A sinkhole discovered over the edge of the Strategic Petroleum Reserve storage facility at Weeks Island salt dome, Louisiana, led to decommissioning the site during 1995--1998, following extensive diagnostics in 1994. The sinkhole resulted from mine-induced fractures in the salt which took may years to develop, eventually causing fresh water to leak into the storage chamber and dissolve the overlying salt, thus causing overburden collapse into the void. Prior to initiating the oil removal, a freeze wall was constructed at depth around the sinkhole in 1995 to prevent water inflow; a freeze plug will remain in place until the minemore » is backfilled with brine in 1997--8, and stability is reached. Residual oil will be removed; environmental monitoring has been initiated and will continue until the facility is completely plugged and abandoned, and environmental surety is achieved.« less

Local initiatives and adaptation to climate change.

PubMed

Blanco, Ana V Rojas

2006-03-01

Climate change is expected to lead to an increase in the number and strength of natural hazards produced by climatic events. This paper presents some examples of the experiences of community-based organisations (CBOs) and non-governmental organisations (NGOs) of variations in climate, and looks at how they have incorporated their findings into the design and implementation of local adaptation strategies. Local organisations integrate climate change and climatic hazards into the design and development of their projects as a means of adapting to their new climatic situation. Projects designed to boost the resilience of local livelihoods are good examples of local adaptation strategies. To upscale these adaptation initiatives, there is a need to improve information exchange between CBOs, NGOs and academia. Moreover, there is a need to bridge the gap between scientific and local knowledge in order to create projects capable of withstanding stronger natural hazards.

A trial of reliable estimation of non-double-couple component of microearthquakes

NASA Astrophysics Data System (ADS)

Imanishi, K.; Uchide, T.

2017-12-01

Although most tectonic earthquakes are caused by shear failure, it has been reported that injection-induced seismicity and earthquakes occurring in volcanoes and geothermal areas contain non double couple (non-DC) components (e.g, Dreger et al., 2000). Also in the tectonic earthquakes, small non-DC components are beginning to be detected (e.g, Ross et al., 2015). However, it is generally limited to relatively large earthquakes that the non-DC component can be estimated with sufficient accuracy. In order to gain further understanding of fluid-driven earthquakes and fault zone properties, it is important to estimate full moment tensor of many microearthquakes with high precision. In the last AGU meeting, we proposed a method that iteratively applies the relative moment tensor inversion (RMTI) (Dahm, 1996) to source clusters improving each moment tensor as well as their relative accuracy. This new method overcomes the problem of RMTI that errors in the mechanism of reference events lead to biased solutions for other events, while taking advantage of RMTI that the source mechanisms can be determined without a computation of Green's function. The procedure is briefly summarized as follows: (1) Sample co-located multiple earthquakes with focal mechanisms, as initial solutions, determined by an ordinary method. (2) Apply the RMTI to estimate the source mechanism of each event relative to those of the other events. (3) Repeat the step 2 for the modified source mechanisms until the reduction of total residual converges. In order to confirm whether the method can resolve non-DC components, we conducted numerical tests on synthetic data. Amplitudes were computed assuming non-DC sources, amplifying by factor between 0.2 and 4 as site effects, and adding 10% random noise. As initial solutions in the step 1, we gave DC sources with arbitrary strike, dip and rake angle. In a test with eight sources at 12 stations, for example, all solutions were successively improved by iteration. Non-DC components were successfully resolved in spite of the fact that we gave DC sources as initial solutions. The application of the method to microearthquakes in geothermal area in Japan will be presented.

Response of the Vegetation-Climate System to High Temperature (Invited)

NASA Astrophysics Data System (ADS)

Berry, J. A.

2009-12-01

High temperature extremes may lead to inhibition of photosynthesis and stomatal closure at the leaf scale. When these responses occur over regional scales, they can initiate a positive feedback loop in the coupled vegetation-climate system. The fraction of net radiation that is used by the land surface to evaporate water decreases leading to deeper, drier boundary layers, fewer clouds, increased solar radiation reaching the surface, and possibility reduced precipitation. These interactions within the vegetation-climate system may amplify natural (or greenhouse gas forced) variations in temperature and further stress the vegetation. Properly modeling of this system depends, among other things, on getting the plant responses to high temperature correct. I will review the current state of this problem and present some studies of rain forest trees to high temperature and drought conducted in the Biosphere 2 enclosure that illustrate how experiments in controlled systems can contribute to our understanding of complex systems to extreme events.

Pathways leading to an immunological disease: systemic lupus erythematosus

PubMed Central

Zharkova, Olga; Celhar, Teja; Cravens, Petra D.; Satterthwaite, Anne B.; Fairhurst, Anna-Marie

2017-01-01

Abstract SLE is a chronic autoimmune disease caused by perturbations of the immune system. The clinical presentation is heterogeneous, largely because of the multiple genetic and environmental factors that contribute to disease initiation and progression. Over the last 60 years, there have been a number of significant leaps in our understanding of the immunological mechanisms driving disease processes. We now know that multiple leucocyte subsets, together with inflammatory cytokines, chemokines and regulatory mediators that are normally involved in host protection from invading pathogens, contribute to the inflammatory events leading to tissue destruction and organ failure. In this broad overview, we discuss the main pathways involved in SLE and highlight new findings. We describe the immunological changes that characterize this form of autoimmunity. The major leucocytes that are essential for disease progression are discussed, together with key mediators that propagate the immune response and drive the inflammatory response in SLE. PMID:28375453

Epigenomics and breast cancer

PubMed Central

Lo, Pang-Kuo

2009-01-01

Breast carcinogenesis involves genetic and epigenetic alterations that cause aberrant gene function. Recent progress in the knowledge of epigenomics has had a profound impact on the understanding of mechanisms leading to breast cancer, and consequently the development of new strategies for diagnosis and treatment of breast cancer. Epigenetic regulation has been known to involve three mutually interacting events – DNA methylation, histone modifications and nucleosomal remodeling. These processes modulate chromatin structure to form euchromatin or heterochromatin, and in turn activate or silence gene expression. Alteration in expression of key genes through aberrant epigenetic regulation in breast cells can lead to initiation, promotion and maintenance of carcinogenesis, and is even implicated in the generation of drug resistance. We currently review known roles of the epigenetic machinery in the development and recurrence of breast cancer. Furthermore, we highlight the significance of epigenetic alterations as predictive biomarkers and as new targets of anticancer therapy. PMID:19072646

Acute pathophysiological processes after ischaemic and traumatic brain injury.

PubMed

Kunz, Alexander; Dirnagl, Ulrich; Mergenthaler, Philipp

2010-12-01

Ischaemic stroke and brain trauma are among the leading causes of mortality and long-term disability in the western world. Enormous endeavours have been made to elucidate the complex pathophysiology of ischaemic and traumatic brain injury with the intention of developing new therapeutic strategies for patients suffering from these devastating diseases. This article reviews the current knowledge on cascades that are activated after ischaemic and traumatic brain injury and that lead to progression of tissue damage. Main attention will be on pathophysiological events initiated after ischaemic stroke including excitotoxicity, oxidative/nitrosative stress, peri-infarct depolarizations, apoptosis and inflammation. Additionally, specific pathophysiological aspects after traumatic brain injury will be discussed along with their similarities and differences to ischaemic brain injury. This article provides prerequisites for understanding the therapeutic strategies for stroke and trauma patients which are addressed in other articles of this issue. Copyright © 2010 Elsevier Ltd. All rights reserved.

High-speed multi-frame laser Schlieren for visualization of explosive events

NASA Astrophysics Data System (ADS)

Clarke, S. A.; Murphy, M. J.; Landon, C. D.; Mason, T. A.; Adrian, R. J.; Akinci, A. A.; Martinez, M. E.; Thomas, K. A.

2007-09-01

High-Speed Multi-Frame Laser Schlieren is used for visualization of a range of explosive and non-explosive events. Schlieren is a well-known technique for visualizing shock phenomena in transparent media. Laser backlighting and a framing camera allow for Schlieren images with very short (down to 5 ns) exposure times, band pass filtering to block out explosive self-light, and 14 frames of a single explosive event. This diagnostic has been applied to several explosive initiation events, such as exploding bridgewires (EBW), Exploding Foil Initiators (EFI) (or slappers), Direct Optical Initiation (DOI), and ElectroStatic Discharge (ESD). Additionally, a series of tests have been performed on "cut-back" detonators with varying initial pressing (IP) heights. We have also used this Diagnostic to visualize a range of EBW, EFI, and DOI full-up detonators. The setup has also been used to visualize a range of other explosive events, such as explosively driven metal shock experiments and explosively driven microjets. Future applications to other explosive events such as boosters and IHE booster evaluation will be discussed. Finite element codes (EPIC, CTH) have been used to analyze the schlieren images to determine likely boundary or initial conditions to determine the temporal-spatial pressure profile across the output face of the detonator. These experiments are part of a phased plan to understand the evolution of detonation in a detonator from initiation shock through run to detonation to full detonation to transition to booster and booster detonation.

Progression is caused by angiotensin II-dependent persistent podocyte loss from destabilized glomeruli

PubMed Central

Fukuda, Akihiro; Wickman, Larysa T.; Venkatareddy, Madhusudan; Sato, Yuji; Chowdhury, Mahboob; Wang, Su Q; Shedden, Kerby; Dysko, Robert; Wiggins, Jocelyn E.; Wiggins, Roger C.

2013-01-01

Podocyte depletion is a major mechanism driving glomerulosclerosis. Progression is the process by which progressive glomerulosclerosis leads to End Stage Kidney Disease (ESKD). We therefore tested the hypothesis that progression to ESKD can be caused by persistent podocyte loss using the human diphtheria toxin transgenic rat model. After initial podocyte injury causing >30% loss of podocytes glomeruli became destabilized, resulting in continuous podocyte loss over time until global podocyte depletion (ESKD) occured. Similar patterns of podocyte depletion were observed in the puromycin aminonucleoside and 5/6 nephrectomy rat models of progression. Angiotensin II blockade prevented continuous podocyte loss and progression (restabilized glomeruli). Discontinuing angiotensin II blockade resulted in recurrent glomerular destabilization, podocyte loss and progression. Reduction in blood pressure alone did not reduce proteinuria or prevent podocyte loss from destabilized glomeruli. The protective effect of angiotensin II blockade could be entirely accounted for by reduction in podocyte loss. These data demonstrate that an initiating event that results in a critical degree of podocyte depletion can destabilize glomeruli by setting in train a superimposed angiotensin II-dependent podocyte loss cycle that accelerates the progression process and results in global podocyte depletion and progression to ESKD. These events can be monitored non-invasively through urine mRNA assays. PMID:21937979

Consensus recommendations on training and competing in the heat.

PubMed

Racinais, S; Alonso, J M; Coutts, A J; Flouris, A D; Girard, O; González-Alonso, J; Hausswirth, C; Jay, O; Lee, J K W; Mitchell, N; Nassis, G P; Nybo, L; Pluim, B M; Roelands, B; Sawka, M N; Wingo, J E; Périard, J D

2015-06-01

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimize performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimize performance is to heat acclimatize. Heat acclimatization should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimize dehydration during exercise. Following the development of commercial cooling systems (e.g., cooling vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organizers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimizing the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events for hydration and body cooling opportunities when competitions are held in the heat. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Consensus recommendations on training and competing in the heat

PubMed Central

Racinais, S; Alonso, J M; Coutts, A J; Flouris, A D; Girard, O; González-Alonso, J; Hausswirth, C; Jay, O; Lee, J K W; Mitchell, N; Nassis, G P; Nybo, L; Pluim, B M; Roelands, B; Sawka, M N; Wingo, J; Périard, J D

2015-01-01

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimise performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimise performance is to heat acclimatise. Heat acclimatisation should comprise repeated exercise-heat exposures over 1–2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimise dehydration during exercise. Following the development of commercial cooling systems (eg, cooling-vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organisers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimising the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events, for hydration and body cooling opportunities, when competitions are held in the heat. PMID:26069301

Unusual RNA plant virus integration in the soybean genome leads to the production of small RNAs.

PubMed

da Fonseca, Guilherme Cordenonsi; de Oliveira, Luiz Felipe Valter; de Morais, Guilherme Loss; Abdelnor, Ricardo Vilela; Nepomuceno, Alexandre Lima; Waterhouse, Peter M; Farinelli, Laurent; Margis, Rogerio

2016-05-01

Horizontal gene transfer (HGT) is known to be a major force in genome evolution. The acquisition of genes from viruses by eukaryotic genomes is a well-studied example of HGT, including rare cases of non-retroviral RNA virus integration. The present study describes the integration of cucumber mosaic virus RNA-1 into soybean genome. After an initial metatranscriptomic analysis of small RNAs derived from soybean, the de novo assembly resulted a 3029-nt contig homologous to RNA-1. The integration of this sequence in the soybean genome was confirmed by DNA deep sequencing. The locus where the integration occurred harbors the full RNA-1 sequence followed by the partial sequence of an endogenous mRNA and another sequence of RNA-1 as an inverted repeat and allowing the formation of a hairpin structure. This region recombined into a retrotransposon located inside an exon of a soybean gene. The nucleotide similarity of the integrated sequence compared to other Cucumber mosaic virus sequences indicates that the integration event occurred recently. We described a rare event of non-retroviral RNA virus integration in soybean that leads to the production of a double-stranded RNA in a similar fashion to virus resistance RNAi plants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: Promising options for prevention and treatment of uterine fibroids?

PubMed Central

Islam, Md Soriful; Akhtar, Most Mauluda; Ciavattini, Andrea; Giannubilo, Stefano Raffaele; Protic, Olga; Janjusevic, Milijana; Procopio, Antonio Domenico; Segars, James H.; Castellucci, Mario; Ciarmela, Pasquapina

2014-01-01

Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70–80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids. PMID:24976593

Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

2007-01-01

Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

The role of long-term strain history on the generation and amplification of inherited heterogeneities in continental lithosphere extensional settings

NASA Astrophysics Data System (ADS)

Morena Salerno, V.; Capitanio, Fabio A.

2017-04-01

The Earth's lithosphere is characters by various types of heterogeneities, at different scales and located at variable depth. They can be represented at crustal level by remnants of earlier tectonics evolution, such as previous orogenetic structures, remains of passive margins and magmatic bodies intrusion, or at deeper level by mantle anisotropies. These heterogeneities can severely affect the stress and strain localization in subsequent continental lithospheric extension and rift basins evolution, hence contributing to the formation of diverse and complex rift basin types and architectures. In order to explain the difference in rift basin and passive margin types, their subsidence patterns and melt production, previous studies have exanimated the role of initial heterogeneities, rheological layering, geothermal gradients, and extension rates during a single rifting event. However, this approach does not consider the previous strain history of many basins that are characterized by multiple rifting events. In this study we use numerical models of a pristine lithosphere undergoing two rifting events separated by cooling, to show the effect of early events on later evolution. The strain histories are controlled by the variation of velocity of boundary displacement during two rifting events. We use both fast and slow first rifting events, followed by a cooling period, producing diverse mechanical heterogeneities at Moho level that represent inherited initial conditions for the second rifting event. These inherited heterogeneities range from several small perturbations distributed along the numerical domain at the end of the slowest first rifting event, to a single large perturbation at the end of first fastest rifting event. In the second rifting event, the inherited heterogeneities are amplified at different degree and time, depending on the velocity of boundary displacement used. To highlight the role of previous strain history, we parametrize the inherited heterogeneities by calculating localization indexes for all the models at the onset of the second rifting event. This calculation embeds the inherited rheology from the previous rift event. We show that the lithosphere progressively localises along the inherited heterogeneities leading to the formation of various rift basin types, ranging from narrow to wide to hyperextended and with variation degrees of symmetry. Our result show that rift basin types and structural styles are strongly affected by inherited heterogeneities generated from previous rifting events, showing cases in which the previous strain history cannot be neglected. The subsidence patterns and melt production result to be very sensitive to the strain history, the type of inherited heterogeneities and their interplay with variation of boundary displacement velocity. Our numerical simulations replicate the first-order features of rift basins and provide a general framework to assess the inherited heterogeneities' role in the interpretation of extensional basins and their evolution.

Lead mobilization during tectonic reactivation of the western Baltic Shield

DOE Office of Scientific and Technical Information (OSTI.GOV)

Romer, R.L.; Wright, J.E.

Lead isotope data from sulfide deposits of the western part of the Baltic Shield define mixing lines in the [sup 206]Pb/[sup 204]Pb-[sup 207]Pb/[sup 204]Pb diagram. Lead from two types of sulfide deposits have been investigated: (1) Exhalative and volcanogenic deposits that are syngenetic with their host rocks; and (2) vein deposits. The syngenetic deposits locally show a very wide range of lead isotopic compositions that reflect a variable addition of highly radiogenic lead, while the vein deposits, although they have radiogenic lead isotopic compositions, exhibit only limited isotopic variations. In different provinces of the shield, both types of deposits fallmore » on the same lead mixing array. The slope of the lead mixing lines varies as a function of the age of basement rocks and the age of the tectonic event which produced the lead mobilization and therefore relates the source rock age with the age of lead mobilization. Calculated mixing ages fall into several short time periods that correspond either to orogenic events or to major phases of continental rifting. The orogenic events are the ca 360--430 Ma Caledonian, ca 900--1100 Ma Sveconorwegian, and the ca 1800--1900 Ma Svecofennian orogenic cycles. The rifting events correspond to the formation of the ca 280 Ma Oslo rift and the Ordovician (ca 450 Ma) graben system in the area of the present Gulf of Bothnia. Each mixing age indicates that lead was mobilized, probably as a consequence of mild thermal disturbances, and that the crust was permeable to lead migration. The data show that the geographic distribution of sulfide deposits with highly radiogenic lead isotopic compositions coincides with old graben systems, orogenic belts, and orogenic forelands on the Baltic Shield. The ages of vein deposits and their geographic distribution demonstrate multiple tectonic reactivation of the interior of the Baltic Shield in response to orogenic events at its margin. 68 refs., 6 refs., 4 tabs.« less

Influence of the drug exposure definition on the assessment of the antipsychotic metabolic impact in patients initially treated with mood-stabilizers.

PubMed

Tournier, Marie; Bégaud, Bernard; Cougnard, Audrey; Auleley, Guy-Robert; Deligne, Jean; Blum-Boisgard, Claudine; Thiébaut, Anne C M; Verdoux, Hélène

2012-07-01

• Metabolic disturbances represent a well-known side effect of second generation antipsychotics. However, studies comparing second generation antipsychotic drugs (SGAPs) and first generation antipsychotic drugs (FGAPs) through administrative databases have shown contrasting findings, which may be attributable to methodological differences. • The definition of antipsychotic exposure impacts on the association between antipsychotics and metabolic risk in studies carried out through administrative databases. • Considering cumulative exposure to antipsychotics or including patients exposed to an antipsychotic drug for months or years is likely to over-represent patients who tolerate the drug well with a depletion of susceptible effects. • Antipsychotic drug exposure is a time-varying determinant and episodes of no use, past use and current use should be distinguished over the study period to avoid any misclassification bias that might lead to misleading findings. To assess the influence of three definitions of antipsychotic exposure on the comparison between first generation (FGAP) and second generation (SGAP) antipsychotic drugs and 'conventional' mood stabilizers towards the risk of metabolic events using (i) a dichotomous measure (exposed/non-exposed over the follow-up), (ii) a categorical measure taking into account the chronology of exposure at the time of the metabolic event (current, recent and no use) and (iii) a continuous measure (cumulative duration). A historical fixed cohort was identified from the 2004-2006 claims database of the French health insurance programme for self-employed workers, including 3172 patients aged 18 years and over who used conventional mood stabilizers over a 3 month period. A metabolic event was defined as an incident dispensing of an anti-diabetic or lipid-lowering drug. A metabolic event occurred in 367 patients (11.6%). At least one FGAP had been prescribed in 29% of patients who did not develop a metabolic event and in 22% of patients who developed a metabolic event. In addition, at least one SGAP had been prescribed in 12% of patients who did not develop a metabolic event and in 7% of patients who developed a metabolic event. Compared with conventional mood stabilizers, the risk of a metabolic event was negatively associated with exposure to SGAPs over the follow-up period (HR 0.53, 95% CI 0.34, 0.82, P= 0.004), positively associated with recent, but not current, exposure to SGAPs (HR 2.1, 95% CI 1.2, 3.7, P= 0.006) and not associated with cumulative duration of SGAPs (HR 1.001, 95% CI 0.999, 1.003, P= 0.20). The definition of exposure to antipsychotics in epidemiological studies exploring their metabolic impact is of paramount importance in understanding this association. Different definitions can lead to opposite and seemingly nonsensical results. Not taking into account past exposure, in order to minimize the depletion of susceptible effects, may lead to absurd results. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Review of complex networks application in hydroclimatic extremes with an implementation to characterize spatio-temporal drought propagation in continental USA

NASA Astrophysics Data System (ADS)

Konapala, Goutam; Mishra, Ashok

2017-12-01

The quantification of spatio-temporal hydroclimatic extreme events is a key variable in water resources planning, disaster mitigation, and preparing climate resilient society. However, quantification of these extreme events has always been a great challenge, which is further compounded by climate variability and change. Recently complex network theory was applied in earth science community to investigate spatial connections among hydrologic fluxes (e.g., rainfall and streamflow) in water cycle. However, there are limited applications of complex network theory for investigating hydroclimatic extreme events. This article attempts to provide an overview of complex networks and extreme events, event synchronization method, construction of networks, their statistical significance and the associated network evaluation metrics. For illustration purpose, we apply the complex network approach to study the spatio-temporal evolution of droughts in Continental USA (CONUS). A different drought threshold leads to a new drought event as well as different socio-economic implications. Therefore, it would be interesting to explore the role of thresholds on spatio-temporal evolution of drought through network analysis. In this study, long term (1900-2016) Palmer drought severity index (PDSI) was selected for spatio-temporal drought analysis using three network-based metrics (i.e., strength, direction and distance). The results indicate that the drought events propagate differently at different thresholds associated with initiation of drought events. The direction metrics indicated that onset of mild drought events usually propagate in a more spatially clustered and uniform approach compared to onsets of moderate droughts. The distance metric shows that the drought events propagate for longer distance in western part compared to eastern part of CONUS. We believe that the network-aided metrics utilized in this study can be an important tool in advancing our knowledge on drought propagation as well as other hydroclimatic extreme events. Although the propagation of droughts is investigated using the network approach, however process (physics) based approaches is essential to further understand the dynamics of hydroclimatic extreme events.

Bcr-Abl and inhibition of apoptosis in chronic myelogenous leukemia cells.

PubMed

Fernandez-Luna, J L

2000-10-01

Chronic myelogenous leukemia (CML) cells are highly resistant to apoptosis induced by chemotherapeutic drugs. The observation that production of Bcr-Abl is the initiating event in CML has focussed attention on the survival signals triggered by this oncogene. A number of signal transducers and transcription factors have been associated with the antiapoptotic phenotype of CML cells, some of which lead to the expression and/or activation of members of the Bcl-2 family of apoptosis modulators, such as Bcl-xL and Bad. In this article, recent advances in understanding the antiapoptotic pathways triggered by Bcr-Abl in CML cells, are discussed.

GEMS Project: A Platform to Investigate Multiple Sclerosis Risk

PubMed Central

Xia, Zongqi; White, Charles C.; Owen, Emily K.; Von Korff, Alina; Clarkson, Sarah R.; McCabe, Cristin A.; Cimpean, Maria; Winn, Phoebe A.; Hoesing, Ashley; Steele, Sonya U.; Cortese, Irene C. M.; Chitnis, Tanuja; Weiner, Howard L.; Reich, Daniel S.; Chibnik, Lori B.; De Jager, Philip L.

2015-01-01

The Genes and Environment in Multiple Sclerosis (GEMS) project establishes a platform to investigate the events leading to MS in at-risk individuals. It has recruited 2,632 first-degree relatives from across the USA. Using an integrated genetic and environmental risk score, we identified subjects with twice the MS risk when compared to the average family member, and we report an initial incidence rate in these subjects that is 30 times greater than that of sporadic MS. We discuss the feasibility of large-scale studies of asymptomatic at-risk subjects that leverage modern tools of subject recruitment to execute collaborative projects. PMID:26583565

Carcinoma-associated fibroblasts: orchestrating the composition of malignancy

PubMed Central

Gascard, Philippe; Tlsty, Thea D.

2016-01-01

The tumor stroma is no longer seen solely as physical support for mutated epithelial cells but as an important modulator and even a driver of tumorigenicity. Within the tumor stromal milieu, heterogeneous populations of fibroblast-like cells, collectively termed carcinoma-associated fibroblasts (CAFs), are key players in the multicellular, stromal-dependent alterations that contribute to malignant initiation and progression. This review focuses on novel insights into the contributions of CAFs to disease progression, emergent events leading to the generation of CAFs, identification of CAF-specific biomarkers predictive of disease outcome, and recent therapeutic approaches aimed at blunting or reverting detrimental protumorigenic phenotypes associated with CAFs. PMID:27151975

Leading a highly visible hospital through a serious reportable event.

PubMed

Erickson, Jeanette Ives

2012-03-01

Most preventable adverse events result from systemic causes, not human error. The senior vice president for patient care/chief nurse at a leading hospital recounts the unnecessary death of a patient and the investigation that followed. Citing the critical importance of a "just culture," this case study offers a blueprint for managing a serious reportable event.

The Role of Solar Wind Structures in the Generation of ULF Waves in the Inner Magnetosphere

NASA Astrophysics Data System (ADS)

Alves, L. R.; Souza, V. M.; Jauer, P. R.; da Silva, L. A.; Medeiros, C.; Braga, C. R.; Alves, M. V.; Koga, D.; Marchezi, J. P.; de Mendonça, R. R. S.; Dallaqua, R. S.; Barbosa, M. V. G.; Rockenbach, M.; Dal Lago, A.; Mendes, O.; Vieira, L. E. A.; Banik, M.; Sibeck, D. G.; Kanekal, S. G.; Baker, D. N.; Wygant, J. R.; Kletzing, C. A.

2017-07-01

The plasma of the solar wind incident upon the Earth's magnetosphere can produce several types of geoeffective events. Among them, an important phenomenon consists of the interrelation of the magnetospheric-ionospheric current systems and the charged-particle population of the Earth's Van Allen radiation belts. Ultra-low-frequency (ULF) waves resonantly interacting with such particles have been claimed to play a major role in the energetic particle flux changes, particularly at the outer radiation belt, which is mainly composed of electrons at relativistic energies. In this article, we use global magnetohydrodynamic simulations along with in situ and ground-based observations to evaluate the ability of two different solar wind transient (SWT) events to generate ULF (few to tens of mHz) waves in the equatorial region of the inner magnetosphere. Magnetic field and plasma data from the Advanced Composition Explorer (ACE) satellite were used to characterize these two SWT events as being a sector boundary crossing (SBC) on 24 September 2013, and an interplanetary coronal mass ejection (ICME) in conjunction with a shock on 2 October 2013. Associated with these events, the twin Van Allen Probes measured a depletion of the outer belt relativistic electron flux concurrent with magnetic and electric field power spectra consistent with ULF waves. Two ground-based observatories apart in 90°C longitude also showed evidence of ULF-wave activity for the two SWT events. Magnetohydrodynamic (MHD) simulation results show that the ULF-like oscillations in the modeled electric and magnetic fields observed during both events are a result from the SWT coupling to the magnetosphere. The analysis of the MHD simulation results together with the observations leads to the conclusion that the two SWT structures analyzed in this article can be geoeffective on different levels, with each one leading to distinct ring current intensities, but both SWTs are related to the same disturbance in the outer radiation belt, i.e. a dropout in the relativistic electron fluxes. Therefore, minor disturbances in the solar wind parameters, such as those related to an SBC, may initiate physical processes that are able to be geoeffective for the outer radiation belt.

Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment.

PubMed

Willis, Rudolph E

2016-09-14

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Initial contact guidance during cell spreading is contractility-independent.

PubMed

Sales, Adrià; Holle, Andrew W; Kemkemer, Ralf

2017-08-02

A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial 'passive' phase of contact guidance, followed by a contractility-dependent 'active' phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

Optimization of the precordial leads of the 12-lead electrocardiogram may improve detection of ST-segment elevation myocardial infarction.

PubMed

Scott, Peter J; Navarro, Cesar; Stevenson, Mike; Murphy, John C; Bennett, Johan R; Owens, Colum; Hamilton, Andrew; Manoharan, Ganesh; Adgey, A A Jennifer

2011-01-01

For the assessment of patients with chest pain, the 12-lead electrocardiogram (ECG) is the initial investigation. Major management decisions are based on the ECG findings, both for attempted coronary artery revascularization and risk stratification. The aim of this study was to determine if the current 6 precordial leads (V(1)-V(6)) are optimally located for the detection of ST-segment elevation in ST-segment elevation myocardial infarction (STEMI). We analyzed 528 (38% anterior [200], 44% inferior [233], and 18% lateral [95]) patients with STEMI with both a 12-lead ECG and an 80-lead body surface map (BSM) ECG (Prime ECG, Heartscape Technologies, Bangor, Northern Ireland). Body surface map was recorded within 15 minutes of the 12-lead ECG during the acute event and before revascularization. ST-segment elevation of each lead on the BSM was compared with the corresponding 12-lead precordial leads (V(1)-V(6)) for anterior STEMI. In addition, for lateral STEMI, leads I and aVL of the BSM were also compared; and limb leads II, III, aVF of the BSM were compared with inferior unipolar BSM leads for inferior STEMI. Leads with the greatest mean ST-segment elevation were selected, and significance was determined by analysis of variance of the mean ST segment. For anterior STEMI, leads V(1), V(2), 32, 42, 51, and 57 had the greatest mean ST elevation. These leads are located in the same horizontal plane as that of V(1) and V(2). Lead 32 had a significantly greater mean ST elevation than the corresponding precordial lead V(3) (P = .012); and leads 42, 51, and 57 were also significantly greater than corresponding leads V(4), V(5), V(6), respectively (P < .001). Similar findings were also found for lateral STEMI. For inferior STEMI, the limb leads of the BSM (II, III, and aVF) had the greatest mean ST-segment elevation; and lead III was significantly superior to the inferior unipolar leads (7, 17, 27, 37, 47, 55, and 61) of the BSM (P < .001). Leads placed on a horizontal strip, in line with leads V(1) and V(2), provided the optimal placement for the diagnosis of anterior and lateral STEMI and appear superior to leads V(3), V(4), V(5), and V(6). This is of significant clinical interest, not only for ease and replication of lead placement but also may lead to increased recruitment of patients eligible for revascularization with none or borderline ST-segment elevation on the initial 12-lead ECG. Copyright © 2011 Elsevier Inc. All rights reserved.

Gain-of-function somatic mutations contribute to inflammation and blood vessel damage that lead to Alzheimer dementia: a hypothesis.

PubMed

Marchesi, Vincent T

2016-02-01

Amyloid deposits are a characteristic feature of advanced Alzheimer dementia (AD), but whether they initiate the disease or are a consequence of it remains an unsettled question. To explore an alternative pathogenic mechanism, I propose that the triggering events that begin the pathogenic cascade are not amyloid deposits but damaged blood vessels caused by inflammatory reactions that lead to ischemia, amyloid accumulation, axonal degeneration, synaptic loss, and eventually irreversible neuronal cell death. Inflammation and blood vessel damage are well recognized complications of AD, but what causes them and why the cerebral microvasculature is affected have never been adequately addressed. Because heritable autosomal dominant mutations of NLRP3, APP, TREX1, NOTCH3, and Col4A1 are known to provoke inflammatory reactions and damage the brain in a wide variety of diseases, I propose that one or more low abundant, gain-of-function somatic mutations of the same 5 gene families damage the microvasculature of the brain that leads to dementia. This implies that the pathogenic triggers that lead to AD are derived not from external invaders or amyloid but from oxidative damage of our own genes. © FASEB.

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy

PubMed Central

de Freitas, Lucas Freitas; Hamblin, Michael R

2016-01-01

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT. PMID:28070154

Proposed Mechanisms of Photobiomodulation or Low-Level Light Therapy.

PubMed

de Freitas, Lucas Freitas; Hamblin, Michael R

2016-01-01

Photobiomodulation (PBM) also known as low-level laser (or light) therapy (LLLT), has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the molecular, cellular, and tissular mechanisms of action. However, in recent years, much knowledge has been gained in this area, which will be summarized in this review. One of the most important chromophores is cytochrome c oxidase (unit IV in the mitochondrial respiratory chain), which contains both heme and copper centers and absorbs light into the near-infra-red region. The leading hypothesis is that the photons dissociate inhibitory nitric oxide from the enzyme, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species, cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, antioxidant enzymes. Stem cells and progenitor cells appear to be particularly susceptible to LLLT.

Capturing the Initiation and Spatial Variability of Runoff on Soils Affected by Wildfire

NASA Astrophysics Data System (ADS)

Martin, D. A.; Wickert, A. D.; Moody, J. A.

2011-12-01

Rainfall after wildfire often leads to intense runoff and erosion, since fire removes ground cover that impedes overland flow and water is unable to efficiently infiltrate into the fire-affected soils. In order to understand the relation between rainfall, infiltration, and runoff, we modified a camera to be triggered by a rain gage to take time-lapse photographs of the ground surface every 10 seconds until the rain stops. This camera allows us to observe directly the patterns of ground surface ponding, the initiation of overland flow, and erosion/deposition during single rainfall events. The camera was deployed on a hillslope (average slope = 23 degrees) that was severely burned by the 2010 Fourmile Canyon Fire near Boulder, Colorado. The camera's field of view is approximately 3 m2. We integrate the photographs with rainfall and overland flow measurements to determine thresholds for the initiation of overland flow and erosion. We have recorded the spatial variability of wetted patches of ground and the connection of these patches together to initiate overland flow. To date we have recorded images for rain storms with 30-minute maximum intensities ranging from 5 mm/h (our threshold to trigger continuous photographs) to 32 mm/h. In the near future we will update the camera's control system to 1) include a clock to enable time-lapse photographs at a lower frequency in addition to the event-triggered images, and 2) to add a radio to allow the camera to be triggered remotely. Radio communication will provide a means of starting the camera in response to non-local events, allowing us to capture images or video of flash flood surge fronts and debris flows, and to synchronize the operations of multiple cameras in the field. Schematics and instructions to build this camera station, which can be used to take either photos or video, are open-source licensed and are available online at http://instaar.colorado.edu/~wickert/atvis. It is our hope that this tool can be used by other researchers to better understand processes in burned watersheds and other sensitive areas that are likely to respond rapidly to rainfall.

Leading Process Branch Instability in Lis1+/− Nonradially Migrating Interneurons

PubMed Central

Gopal, Pallavi P.; Simonet, Jacqueline C.; Shapiro, William

2010-01-01

Mammalian forebrain development requires extensive migration, yet the mechanisms through which migrating neurons sense and respond to guidance cues are not well understood. Similar to the axon growth cone, the leading process and branches of neurons may guide migration, but the cytoskeletal events that regulate branching are unknown. We have previously shown that loss of microtubule-associated protein Lis1 reduces branching during migration compared with wild-type neurons. Using time-lapse imaging of Lis1+/− and Lis1+/+ cells migrating from medial ganglionic eminence explant cultures, we show that the branching defect is not due to a failure to initiate branches but a defect in the stabilization of new branches. The leading processes of Lis1+/− neurons have reduced expression of stabilized, acetylated microtubules compared with Lis1+/+ neurons. To determine whether Lis1 modulates branch stability through its role as the noncatalytic β regulatory subunit of platelet-activating factor (PAF) acetylhydrolase 1b, exogenous PAF was applied to wild-type cells. Excess PAF added to wild-type neurons phenocopies the branch instability observed in Lis1+/− neurons, and a PAF antagonist rescues leading process branching in Lis1+/− neurons. These data highlight a role for Lis1, acting through the PAF pathway, in leading process branching and microtubule stabilization. PMID:19861636

Lead-Free Double-Base Propellant for the 2.75 Inch Rocket Motor

NASA Technical Reports Server (NTRS)

Magill, B. T.; Nauflett, G. W.; Furrow, K. W.

2000-01-01

The current MK 66 2.75 inch Rocket Motor double-base propellant contains the lead-based ballistic modifier LC-12-15 to achieve the desired plateau and mesa burning rate characteristics. The use of lead compounds poses a concern for the environment and for personal safety due to the metal's toxic nature when introduced into the atmosphere by propellant manufacture, rocket motor firing, and disposal. Copper beta-resorcylate (copper 2,4-di-hydroxy-benzoate) was successfully used in propellant as a simple modifier in the mid 1970's. This and other compounds have also been mixed with lead salts to obtain more beneficial ballistic results. Synthesized complexes of lead and copper compounds soon replaced the mixtures. The complexes incorporate the lead, copper lack of organic liquids, which allows for easier propellant processing. About ten years ago, the Indian Head Division, Naval Surface Warfare Center (NSWC), initiated an effort to develop a lead-free propellant for use in missile systems. Several lead-free propellant candidate formulations were developed. About five years ago, NSWC, in conjunction with Alliant Techsystems, Radford Army Ammunition Plant, continued ballistic modifier investigations. A four component ballistic modifier system without lead for double-base propellants that provide adequate plateau and mesa burn rate characteristics was developed and patented. The ballistic modifier's system contains bismuth subsalicylate, 1.5 percent; copper salicylate, 1.0 percent, copper stannate, 0.77 percent; and carbon black, 0.1 percent. Action time and impulse data obtained through multiple static firings indicate that the new lead-free double-base propellant, while not a match for NOSIH-AA-2, will be a very suitable replacement in the 2.75 inch Rocket Motor. Accelerated aging of the double-base propellant containing the lead-free ballistic modifier showed that it had a much higher rate of stabilizer depletion than the AA-2. A comprehensive study showed that an increased rate of stabilizer depletion occurred in propellants containing monobasic copper salicylate. The study also showed that propellants containing a mixture of bismuth subsalicylate and copper salicylate, had only about one-half the stabilizer depletion rate than those with copper salicylate alone. The copper salicylate catalyzes the decomposition of nitroglycerin, which triggers a chain of events leading to the increased rate of stabilizer depletion. A program has been initiated to coat the ballistic modifier, thus isolating it from the nitroglycerin.

Validation in the Absence of Observed Events

DOE PAGES

Lathrop, John; Ezell, Barry

2015-07-22

Here our paper addresses the problem of validating models in the absence of observed events, in the area of Weapons of Mass Destruction terrorism risk assessment. We address that problem with a broadened definition of “Validation,” based on “backing up” to the reason why modelers and decision makers seek validation, and from that basis re-define validation as testing how well the model can advise decision makers in terrorism risk management decisions. We develop that into two conditions: Validation must be based on cues available in the observable world; and it must focus on what can be done to affect thatmore » observable world, i.e. risk management. That in turn leads to two foci: 1.) the risk generating process, 2.) best use of available data. Based on our experience with nine WMD terrorism risk assessment models, we then describe three best use of available data pitfalls: SME confidence bias, lack of SME cross-referencing, and problematic initiation rates. Those two foci and three pitfalls provide a basis from which we define validation in this context in terms of four tests -- Does the model: … capture initiation? … capture the sequence of events by which attack scenarios unfold? … consider unanticipated scenarios? … consider alternative causal chains? Finally, we corroborate our approach against three key validation tests from the DOD literature: Is the model a correct representation of the simuland? To what degree are the model results comparable to the real world? Over what range of inputs are the model results useful?« less

A laboratory nanoseismological study on deep-focus earthquake micromechanics

PubMed Central

Wang, Yanbin; Zhu, Lupei; Shi, Feng; Schubnel, Alexandre; Hilairet, Nadege; Yu, Tony; Rivers, Mark; Gasc, Julien; Addad, Ahmed; Deldicque, Damien; Li, Ziyu; Brunet, Fabrice

2017-01-01

Global earthquake occurring rate displays an exponential decay down to ~300 km and then peaks around 550 to 600 km before terminating abruptly near 700 km. How fractures initiate, nucleate, and propagate at these depths remains one of the greatest puzzles in earth science, as increasing pressure inhibits fracture propagation. We report nanoseismological analysis on high-resolution acoustic emission (AE) records obtained during ruptures triggered by partial transformation from olivine to spinel in Mg2GeO4, an analog to the dominant mineral (Mg,Fe)2SiO4 olivine in the upper mantle, using state-of-the-art seismological techniques, in the laboratory. AEs’ focal mechanisms, as well as their distribution in both space and time during deformation, are carefully analyzed. Microstructure analysis shows that AEs are produced by the dynamic propagation of shear bands consisting of nanograined spinel. These nanoshear bands have a near constant thickness (~100 nm) but varying lengths and self-organize during deformation. This precursory seismic process leads to ultimate macroscopic failure of the samples. Several source parameters of AE events were extracted from the recorded waveforms, allowing close tracking of event initiation, clustering, and propagation throughout the deformation/transformation process. AEs follow the Gutenberg-Richter statistics with a well-defined b value of 1.5 over three orders of moment magnitudes, suggesting that laboratory failure processes are self-affine. The seismic relation between magnitude and rupture area correctly predicts AE magnitude at millimeter scales. A rupture propagation model based on strain localization theory is proposed. Future numerical analyses may help resolve scaling issues between laboratory AE events and deep-focus earthquakes. PMID:28776024

Validation in the Absence of Observed Events.

PubMed

Lathrop, John; Ezell, Barry

2016-04-01

This article addresses the problem of validating models in the absence of observed events, in the area of weapons of mass destruction terrorism risk assessment. We address that problem with a broadened definition of "validation," based on stepping "up" a level to considering the reason why decisionmakers seek validation, and from that basis redefine validation as testing how well the model can advise decisionmakers in terrorism risk management decisions. We develop that into two conditions: validation must be based on cues available in the observable world; and it must focus on what can be done to affect that observable world, i.e., risk management. That leads to two foci: (1) the real-world risk generating process, and (2) best use of available data. Based on our experience with nine WMD terrorism risk assessment models, we then describe three best use of available data pitfalls: SME confidence bias, lack of SME cross-referencing, and problematic initiation rates. Those two foci and three pitfalls provide a basis from which we define validation in this context in terms of four tests--Does the model: … capture initiation? … capture the sequence of events by which attack scenarios unfold? … consider unanticipated scenarios? … consider alternative causal chains? Finally, we corroborate our approach against three validation tests from the DOD literature: Is the model a correct representation of the process to be simulated? To what degree are the model results comparable to the real world? Over what range of inputs are the model results useful? © 2015 Society for Risk Analysis.

The Eruption Forecasting Information System (EFIS) database project

NASA Astrophysics Data System (ADS)

Ogburn, Sarah; Harpel, Chris; Pesicek, Jeremy; Wellik, Jay; Pallister, John; Wright, Heather

2016-04-01

The Eruption Forecasting Information System (EFIS) project is a new initiative of the U.S. Geological Survey-USAID Volcano Disaster Assistance Program (VDAP) with the goal of enhancing VDAP's ability to forecast the outcome of volcanic unrest. The EFIS project seeks to: (1) Move away from relying on the collective memory to probability estimation using databases (2) Create databases useful for pattern recognition and for answering common VDAP questions; e.g. how commonly does unrest lead to eruption? how commonly do phreatic eruptions portend magmatic eruptions and what is the range of antecedence times? (3) Create generic probabilistic event trees using global data for different volcano 'types' (4) Create background, volcano-specific, probabilistic event trees for frequently active or particularly hazardous volcanoes in advance of a crisis (5) Quantify and communicate uncertainty in probabilities A major component of the project is the global EFIS relational database, which contains multiple modules designed to aid in the construction of probabilistic event trees and to answer common questions that arise during volcanic crises. The primary module contains chronologies of volcanic unrest, including the timing of phreatic eruptions, column heights, eruptive products, etc. and will be initially populated using chronicles of eruptive activity from Alaskan volcanic eruptions in the GeoDIVA database (Cameron et al. 2013). This database module allows us to query across other global databases such as the WOVOdat database of monitoring data and the Smithsonian Institution's Global Volcanism Program (GVP) database of eruptive histories and volcano information. The EFIS database is in the early stages of development and population; thus, this contribution also serves as a request for feedback from the community.

Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events.

PubMed

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Moriyama, Mitsuhiko; Kato, Naoya

2018-03-23

Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen. Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks. Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs.

Successful retreatment with grazoprevir and elbasvir for patients infected with hepatitis C virus genotype 1b, who discontinued prior treatment with NS5A inhibitor-including regimens due to adverse events

PubMed Central

Kanda, Tatsuo; Yasui, Shin; Nakamura, Masato; Nakamoto, Shingo; Takahashi, Koji; Wu, Shuang; Sasaki, Reina; Haga, Yuki; Ogasawara, Sadahisa; Saito, Tomoko; Kobayashi, Kazufumi; Kiyono, Soichiro; Ooka, Yoshihiko; Suzuki, Eiichiro; Chiba, Tetsuhiro; Maruyama, Hitoshi; Moriyama, Mitsuhiko; Kato, Naoya

2018-01-01

Background Sustained virologic response (SVR) by interferon and interferon-free treatment can results in the reduction of advanced liver fibrosis and the occurrence of hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). Recent interferon-free treatment for HCV shortens the duration of treatment and leads to higher SVR rates, without any serious adverse events. However, it is important to retreat patients who have had treatment-failure with HCV non-structural protein 5A (NS5A) inhibitor-including regimens. Combination of sofosbuvir and ledipasvir only leads to approximately 100% SVR rates in HCV genotype (GT1b), NS5A inhibitor-naïve patients in Japan. This combination is not an indication for severe renal disease or heart disease, and these patients should be treated or retreated with a different regimen. Case summary Retreatment with HCV non-structural protein 3/4A inhibitor, grazoprevir, and HCV NS5A inhibitor, elbasvir, successfully eradicated HCV RNA in three patients with HCV genotype 1b infection who discontinued prior interferon-free treatments including HCV NS5A inhibitors due to adverse events within 2 weeks. Conclusion Retreatment with the 12-week combination regimen of grazoprevir and elbasvir is effective for HCV GT1b patients who discontinue the HCV NS5A inhibitor-including regimens within 2 weeks. The treatment response may be related to the short duration of initial treatment, which did not produce treatment-emergent RASs. PMID:29662642

DISTAG/TBCCd1 Is Required for Basal Cell Fate Determination in Ectocarpus[OPEN

PubMed Central

Godfroy, Olivier; Uji, Toshiki; Nagasato, Chikako; Colin, Sebastien; Mignerot, Laure; Motomura, Taizo

2017-01-01

Brown algae are one of the most developmentally complex groups within the eukaryotes. As in many land plants and animals, their main body axis is established early in development, when the initial cell gives rise to two daughter cells that have apical and basal identities, equivalent to shoot and root identities in land plants, respectively. We show here that mutations in the Ectocarpus DISTAG (DIS) gene lead to loss of basal structures during both the gametophyte and the sporophyte generations. Several abnormalities were observed in the germinating initial cell in dis mutants, including increased cell size, disorganization of the Golgi apparatus, disruption of the microtubule network, and aberrant positioning of the nucleus. DIS encodes a TBCCd1 protein, which has a role in internal cell organization in animals, Chlamydomonas reinhardtii, and trypanosomes. Our study highlights the key role of subcellular events within the germinating initial cell in the determination of apical/basal cell identities in a brown alga and emphasizes the remarkable functional conservation of TBCCd1 in regulating internal cell organization across extremely distant eukaryotic groups. PMID:29208703

Genetic evidence supporting a critical role of endothelial caveolin-1 during the progression of atherosclerosis

PubMed Central

Fernández-Hernando, Carlos; Yu, Jun; Suárez, Yajaira; Rahner, Christoph; Dávalos, Alberto; Lasunción, Miguel A.; Sessa, William C.

2009-01-01

SUMMARY The accumulation of LDL-derived cholesterol in the artery wall is the initiating event that causes atherosclerosis. However, the mechanisms that lead to the initiation of atherosclerosis are still poorly understood. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in promoting atherogenesis. Mice were generated lacking Cav-1 and apoE but expressing endothelial-specific Cav-1 in the double knockout background. Genetic ablation of Cav-1 on an apoE knockout background inhibits the progression of atherosclerosis while re-expression of Cav-1 in the endothelium promotes lesion expansion. Mechanistically, the loss of Cav-1 reduces LDL infiltration into the artery wall, promotes nitric oxide production and reduces the expression of leukocyte adhesion molecules, effects completely reversed in transgenic mice. In summary, this unique model provides physiological evidence supporting the important role of endothelial Cav-1 expression in regulating the entry of LDL into the vessel wall and the initiation of atherosclerosis. PMID:19583953

Observables for longitudinal flow correlations in heavy-ion collisions

DOE PAGES

Jia, Jiangyong; Huo, Peng; Ma, Guoliang; ...

2017-06-06

In this paper, we propose several new observables/correlators, based on correlations between two or more subevents separated in pseudorapidity η, to study the longitudinal flow fluctuations. We show that these observables are sensitive to the event-by-event fluctuations, as a function of η, of the initial condition as well as the nonlinear mode-mixing effects. Finally, experimental measurement of these observables shall provide important new constraints on the boost-variant event-by-event initial conditions required by all 3+1-dimensional viscous hydrodynamics models.

The RenTg mice: a powerful tool to study renin-dependent chronic kidney disease.

PubMed

Huby, Anne-Cecile; Kavvadas, Panagiotis; Alfieri, Carlo; Abed, Ahmed; Toubas, Julie; Rastaldi, Maria-Pia; Dussaule, Jean-Claude; Chatziantoniou, Christos; Chadjichristos, Christos E

2012-01-01

Several studies have shown that activation of the renin-angiotensin system may lead to hypertension, a major risk factor for the development of chronic kidney disease (CKD). The existing hypertension-induced CDK mouse models are quite fast and consequently away from the human pathology. Thus, there is an urgent need for a mouse model that can be used to delineate the pathogenic process leading to progressive renal disease. The objective of this study was dual: to investigate whether mice overexpressing renin could mimic the kinetics and the physiopathological characteristics of hypertension-induced renal disease and to identify cellular and/or molecular events characterizing the different steps of the progression of CKD. We used a novel transgenic strain, the RenTg mice harboring a genetically clamped renin transgene. At 3 months, heterozygous mice are hypertensive and slightly albuminuric. The expression of adhesion markers such as vascular cell adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 are increased in the renal vasculature indicating initiation of endothelial dysfunction. At 5 months, perivascular and periglomerular infiltrations of macrophages are observed. These early renal vascular events are followed at 8 months by leukocyte invasion, decreased expression of nephrin, increased expression of KIM-1, a typical protein of tubular cell stress, and of several pro-fibrotic agents of the TGFβ family. At 12 months, mice display characteristic structural alterations of hypertensive renal disease such as glomerular ischemia, glomerulo- and nephroangio-sclerosis, mesangial expansion and tubular dilation. The RenTg strain develops CKD progressively. In this model, endothelial dysfunction is an early event preceding the structural and fibrotic alterations which ultimately lead to the development of CKD. This model can provide new insights into the mechanisms of chronic renal failure and help to identify new targets for arresting and/or reversing the development of the disease.

A new method for assessing the impact of medial temporal lobe amnesia on the characteristics of generated autobiographical events.

PubMed

Lenton-Brym, Ariella; Kurczek, Jake; Rosenbaum, R Shayna; Sheldon, Signy

2016-05-01

Constructing autobiographical events involves an initial phase of event selection, in which a memory or imagined future event is initially brought to mind, followed by a phase of elaboration, in which an individual accesses detailed knowledge specific to the event. While considerable research demonstrates the importance of the medial temporal lobes (MTL) in the later phase, its role in initial event selection is unknown. The present study is the first to investigate the role of the MTL in event selection by assessing whether individuals with MTL lesions select qualitatively different events for remembering and imagining than matched control participants. To do so, we created "event captions" that reflected the type of events selected for an autobiographical event narrative task by four individuals with MTL amnesia and control counterparts. Over 450 online raters assessed these event captions on qualitative dimensions known to vary with autobiographical recall (frequency, significance, emotionality, imageability, and uniqueness). Our critical finding was that individuals with MTL amnesia were more prone to select events that were rated as more frequently occurring than healthy control participants. We interpret this finding as evidence that people with impaired episodic memory from MTL damage compensate for their compromised ability to recall detailed information by relying more heavily on semantic memory processes to select generalized events. We discuss the implications for theoretical models of memory and methodological approaches to studying autobiographical memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Using crustal thickness and subsidence history on the Iberia-Newfoundland margins to constrain lithosphere deformation modes during continental breakup

NASA Astrophysics Data System (ADS)

Jeanniot, Ludovic; Kusznir, Nick; Manatschal, Gianreto; Mohn, Geoffroy

2014-05-01

Observations at magma-poor rifted margins such as Iberia-Newfoundland show a complex lithosphere deformation history during continental breakup and seafloor spreading initiation leading to complex OCT architecture with hyper-extended continental crust and lithosphere, exhumed mantle and scattered embryonic oceanic crust and continental slivers. Initiation of seafloor spreading requires both the rupture of the continental crust and lithospheric mantle, and the onset of decompressional melting. Their relative timing controls when mantle exhumation may occur; the presence or absence of exhumed mantle provides useful information on the timing of these events and constraints on lithosphere deformation modes. A single lithosphere deformation mode leading to continental breakup and sea-floor spreading cannot explain observations. We have determined the sequence of lithosphere deformation events for two profiles across the present-day conjugate Iberia-Newfoundland margins, using forward modelling of continental breakup and seafloor spreading initiation calibrated against observations of crustal basement thickness and subsidence. Flow fields, representing a sequence of lithosphere deformation modes, are generated by a 2D finite element viscous flow model (FeMargin), and used to advect lithosphere and asthenosphere temperature and material. FeMargin is kinematically driven by divergent deformation in the upper 15-20 km of the lithosphere inducing passive upwelling beneath that layer; extensional faulting and magmatic intrusions deform the topmost upper lithosphere, consistent with observations of deformation processes occurring at slow spreading ocean ridges (Cannat, 1996). Buoyancy enhanced upwelling, as predicted by Braun et al. (2000) is also kinematically included in the lithosphere deformation model. Melt generation by decompressional melting is predicted using the parameterization and methodology of Katz et al. (2003). The distribution of lithosphere deformation, the contribution of buoyancy driven upwelling and their spatial and temporal evolution including lateral migration are determined by using a series of numerical experiments, tested and calibrated against observations of crustal thicknesses and water-loaded subsidence. Pure-shear widths exert a strong control on the timing of crustal rupture and melt initiation; to satisfy OCT architecture, subsidence and mantle exhumation, we need to focus the deformation from a broad to a narrow region. The lateral migration of the deformation flow axis has an important control on the rupture of continental crust and lithosphere, melt initiation, their relative timing, the resulting OCT architecture and conjugate margin asymmetry. The numerical models are used to predict margin isostatic response and subsidence history.

Current sheet formation in a sheared force-free-magnetic field. [in sun

NASA Technical Reports Server (NTRS)

Wolfson, Richard

1989-01-01

This paper presents the results of a study showing how continuous shearing motion of magnetic footpoints in a tenuous, infinitely conducting plasma can lead to the development of current sheets, despite the absence of such sheets or even of neutral points in the initial state. The calculations discussed here verify the earlier suggestion by Low and Wolfson (1988) that extended current sheets should form due to the shearing of a force-free quadrupolar magnetic field. More generally, this work augments earlier studies suggesting that the appearance of discontinuities - current sheets - may be a necessary consequence of the topological invariance imposed on the magnetic field geometry of an ideal MHD system by virtue of its infinite conductivity. In the context of solar physics, the work shows how the gradual and continuous motion of magnetic footpoints at the solar photosphere may lead to the buildup of magnetic energy that can then be released explosively when finite conductivity effects become important and lead to the rapid dissipation of current sheets. Such energy release may be important in solar flares, coronal mass ejections, and other eruptive events.

Investigating NWP initialization sensitivities in heavy precipitation events

NASA Astrophysics Data System (ADS)

Frediani, M. E. B.; Anagnostou, E. N.; Papadopoulos, A.

2010-09-01

This study aims to investigate the effect of different types of model initialization applied to extreme storms simulations. Storms with extreme precipitation can usually produce flash floods that cause several damages to the society. Lives and property are destroyed from the landslides when they could be speared if forecasted a few hours in advance. The forecasts depend on several factors; among them the initialization fields play an important role. These fields are the starting point for the simulation and therefore it controls the quality of the forecast. This study evaluates the sensitivities of WRF to the initialization from two perspectives, (1) resolution and (2) initial atmospheric fields. Two storms that lead to flash flood are simulated. The first one happened in Northeast Italy in 04/09/2009 (NI), and the second in Germany, in 02/06/2008 (GE). These storms present contrasting characteristics, NI was a maritime originated storm enhanced by local orography while GE was a typical summer convection. Three different sources of atmospheric fields defining the initial conditions are applied: (a) ECMWF operational analysis at resolution of 0.25 deg, (b) GFS operational analysis at 0.5deg and (c) LAPS analysis at ~15km, produced operationally at HCMR. The rainfall forecasted is compared against in situ ground radar and surface rain gauges observations through a set of quantitative precipitation forecast scores.

The canopy interception-landslide initiation conundrum: insight from a tropical secondary forest in northern Thailand

NASA Astrophysics Data System (ADS)

Sidle, Roy C.; Ziegler, Alan D.

2017-01-01

The interception and smoothing effect of forest canopies on pulses of incident rainfall and its delivery to the soil has been suggested as a factor in moderating peak pore water pressure in soil mantles, thus reducing the risk of shallow landslides. Here we provide 3 years of rainfall and throughfall data in a tropical secondary dipterocarp forest characterized by few large trees in northern Thailand, along with selected soil moisture dynamics, to address this issue. Throughfall was an estimated 88 % of rainfall, varying from 86 to 90 % in individual years. Data from 167 events demonstrate that canopy interception was only weakly associated (via a nonlinear relationship) with total event rainfall, but not significantly correlated with duration, mean intensity, or antecedent 2-day precipitation (API2). Mean interception during small events (≤ 35 mm) was 17 % (n = 135 events) compared with only 7 % for large events (> 35 mm; n = 32). Examining small temporal intervals within the largest and highest intensity events that would potentially trigger landslides revealed complex patterns of interception. The tropical forest canopy had little smoothing effect on incident rainfall during the largest events. During events with high peak intensities, high wind speeds, and/or moderate-to-high pre-event wetting, measured throughfall was occasionally higher than rainfall during large event peaks, demonstrating limited buffering. However, in events with little wetting and low-to-moderate wind speed, early event rainfall peaks were buffered by the canopy. As rainfall continued during most large events, there was little difference between rainfall and throughfall depths. A comparison of both rainfall and throughfall depths to conservative mean intensity-duration thresholds for landslide initiation revealed that throughfall exceeded the threshold in 75 % of the events in which rainfall exceeded the threshold for both wet and dry conditions. Throughfall intensity for the 11 largest events (rainfall = 65-116 mm) plotted near or above the intensity-duration threshold for landslide initiation during wet conditions; 5 of the events were near or above the threshold for dry conditions. Soil moisture responses during large events were heavily and progressively buffered at depths of 1 to 2 m, indicating that the timescale of any short-term smoothing of peak rainfall inputs (i.e., ≤ 1 h) has little influence on peak pore water pressure at depths where landslides would initiate in this area. Given these findings, we conclude that canopy interception would have little effect on mitigating shallow landslide initiation during the types of monsoon rainfall conditions in this and similar tropical secondary forest sites.

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2015-10-01

RAVEN is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncertainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters that need tomore » be perturbed are accessible by inputs files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN has started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assessment capability to RELAP-7, currently under development at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activaties are currently ongoing for coupling RAVEN with software such as RELAP5-3D, etc. The aim of this document is the explanation of the input requirements, focalizing on the input structure.« less

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2016-02-01

RAVEN is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncertainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters that need tomore » be perturbed are accessible by input files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assessment capability to RELAP-7, currently under development at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activates are currently ongoing for coupling RAVEN with software such as RELAP5-3D, etc. The aim of this document is the explanation of the input requirements, focusing on the input structure.« less

RAVEN User Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mandelli, Diego; Rabiti, Cristian; Cogliati, Joshua Joseph

2017-03-01

RAVEN is a generic software framework to perform parametric and probabilistic analy- sis based on the response of complex system codes. The initial development was aimed to provide dynamic risk analysis capabilities to the Thermo-Hydraulic code RELAP-7, currently under development at the Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose probabilistic and uncer- tainty quantification platform, capable to agnostically communicate with any system code. This agnosticism includes providing Application Programming Interfaces (APIs). These APIs are used to allow RAVEN to interact with any code as long as all the parameters thatmore » need to be perturbed are accessible by inputs files or via python interfaces. RAVEN is capable of investigating the system response, and investigating the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused to- ward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. The development of RAVEN has started in 2012, when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework became stronger. RAVEN principal assignment is to provide the necessary software and algorithms in order to employ the concept developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just the individuation of the frequency of an event potentially leading to a system failure, but the closeness (or not) to key safety-related events. Hence, the approach is in- terested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. for an important process such as peak pressure in a pipe) is exceeded under certain conditions. The initial development of RAVEN has been focused on providing dynamic risk assess- ment capability to RELAP-7, currently under develop-ment at the INL and, likely, future replacement of the RELAP5-3D code. Most the capabilities that have been implemented having RELAP-7 as principal focus are easily deployable for other system codes. For this reason, several side activates are currently ongoing for coupling RAVEN with soft- ware such as RELAP5-3D, etc. The aim of this document is the explaination of the input requirements, focalizing on the input structure.« less

Assessing the Skill of Chlorophyll Forecasts: Latest Development and Challenges Ahead Using the Case of the Equatorial Pacific

NASA Technical Reports Server (NTRS)

Rousseaux, Cecile S.; Gregg, Watson W.

2018-01-01

Using a global ocean biogeochemical model combined with a forecast of physical oceanic and atmospheric variables from the NASA Global Modeling and Assimilation Office, we assess the skill of a chlorophyll concentrations forecast in the Equatorial Pacific for the period 2012-2015 with a focus on the forecast of the onset of the 2015 El Nino event. Using a series of retrospective 9-month hindcasts, we assess the uncertainties of the forecasted chlorophyll by comparing the monthly total chlorophyll concentration from the forecast with the corresponding monthly ocean chlorophyll data from the Suomi-National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (S-NPP VIIRS) satellite. The forecast was able to reproduce the phasing of the variability in chlorophyll concentration in the Equatorial Pacific, including the beginning of the 2015-2016 El Nino. The anomaly correlation coefficient (ACC) was significant (p less than 0.05) for forecast at 1-month (R=0.33), 8-month (R=0.42) and 9-month (R=0.41) lead times. The root mean square error (RMSE) increased from 0.0399 microgram chl L(exp -1) for the 1-month lead forecast to a maximum of 0.0472 microgram chl L(exp -1) for the 9-month lead forecast indicating that the forecast of the amplitude of chlorophyll concentration variability was getting worse. Forecasts with a 3-month lead time were on average the closest to the S-NPP VIIRS data (23% or 0.033 microgram chl L(exp -1)) while the forecast with a 9-month lead time were the furthest (31% or 0.042 microgram chl L(exp -1)). These results indicate the potential for forecasting chlorophyll concentration in this region but also highlights various deficiencies and suggestions for improvements to the current biogeochemical forecasting system. This system provides an initial basis for future applications including the effects of El Nino events on fisheries and other ocean resources given improvements identified in the analysis of these results.

Forecasting Ocean Chlorophyll in the Equatorial Pacific.

PubMed

Rousseaux, Cecile S; Gregg, Watson W

2017-01-01

Using a global ocean biogeochemical model combined with a forecast of physical oceanic and atmospheric variables from the NASA Global Modeling and Assimilation Office, we assess the skill of a chlorophyll concentrations forecast in the Equatorial Pacific for the period 2012-2015 with a focus on the forecast of the onset of the 2015 El Niño event. Using a series of retrospective 9-month hindcasts, we assess the uncertainties of the forecasted chlorophyll by comparing the monthly total chlorophyll concentration from the forecast with the corresponding monthly ocean chlorophyll data from the Suomi-National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (S-NPP VIIRS) satellite. The forecast was able to reproduce the phasing of the variability in chlorophyll concentration in the Equatorial Pacific, including the beginning of the 2015-2016 El Niño. The anomaly correlation coefficient (ACC) was significant ( p < 0.05) for forecast at 1-month ( R = 0.33), 8-month ( R = 0.42) and 9-month ( R = 0.41) lead times. The root mean square error (RMSE) increased from 0.0399 μg chl L -1 for the 1-month lead forecast to a maximum of 0.0472 μg chl L -1 for the 9-month lead forecast indicating that the forecast of the amplitude of chlorophyll concentration variability was getting worse. Forecasts with a 3-month lead time were on average the closest to the S-NPP VIIRS data (23% or 0.033 μg chl L -1 ) while the forecast with a 9-month lead time were the furthest (31% or 0.042 μg chl L -1 ). These results indicate the potential for forecasting chlorophyll concentration in this region but also highlights various deficiencies and suggestions for improvements to the current biogeochemical forecasting system. This system provides an initial basis for future applications including the effects of El Niño events on fisheries and other ocean resources given improvements identified in the analysis of these results.

Linking cases of illegal shootings of the endangered California condor using stable lead isotope analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkelstein, Myra E., E-mail: myraf@ucsc.edu; Kuspa, Zeka E.; Welch, Alacia

Lead poisoning is preventing the recovery of the critically endangered California condor (Gymnogyps californianus) and lead isotope analyses have demonstrated that ingestion of spent lead ammunition is the principal source of lead poisoning in condors. Over an 8 month period in 2009, three lead-poisoned condors were independently presented with birdshot embedded in their tissues, evidencing they had been shot. No information connecting these illegal shooting events existed and the timing of the shooting(s) was unknown. Using lead concentration and stable lead isotope analyses of feathers, blood, and recovered birdshot, we observed that: i) lead isotope ratios of embedded shot frommore » all three birds were measurably indistinguishable from each other, suggesting a common source; ii) lead exposure histories re-constructed from feather analysis suggested that the shooting(s) occurred within the same timeframe; and iii) two of the three condors were lead poisoned from a lead source isotopically indistinguishable from the embedded birdshot, implicating ingestion of this type of birdshot as the source of poisoning. One of the condors was subsequently lead poisoned the following year from ingestion of a lead buckshot (blood lead 556 µg/dL), illustrating that ingested shot possess a substantially greater lead poisoning risk compared to embedded shot retained in tissue (blood lead ∼20 µg/dL). To our knowledge, this is the first study to use lead isotopes as a tool to retrospectively link wildlife shooting events. - Highlights: • We conducted a case-based analysis of illegal shootings of California condors. • Blood and feather Pb isotopes were used to reconstruct the illegal shooting events. • Embedded birdshot from the three condors had the same Pb isotope ratios. • Feather and blood Pb isotopes indicated that the condors were shot in a common event. • Ingested shot causes substantially greater lead exposure compared to embedded shot.« less

Influential factors on debris flow events and hillslope-channel connectivity in Alpine regions: case studies from two Alpine regions in Styria, Austria

NASA Astrophysics Data System (ADS)

Traper, Sandra; Pöppl, Ronald; Rascher, Eric; Sass, Oliver

2016-04-01

In recent times different types of natural disasters like debris flow events have attracted increasing attention worldwide, since they can cause great damage and loss of infrastructure or even lives is not unusual when it comes to such an event. The engagement with debris flows is especially important in mountainous areas like Austria, since Alpine regions have proved to be particularly prone to the often harmful consequences of such events because of increasing settlement of previously uninhabited regions. Due to those frequently damaging effects of debris flows, research on this kind of natural disaster often focuses on mitigation and recovery measures after an event and on how to restore the initial situation. However, a view on the situation of an area, where severe debris flows recently occurred and are well documented, before the actual event can aid in discovering important preparatory factors that contribute to initiating debris flows and hillslope-channel connectivity in the first place. Valuable insights into the functioning and preconditions of debris flows and their potential connectivity to the main channel can be gained. The study focuses on two geologically different areas in the Austrian Alps, which are both prone to debris flows and have experienced rather severe events recently. Based on data from debris flow events in two regions in Styria (Austria), the Kleinsölk and the Johnsbach valleys, the aim of the study is to identify factors which influence the development of debris flows and the potential of such debris flows to reach the main channel potentially clogging up the river (hillslope-channel connectivity). The degree of hillslope-channel coupling was verified in extensive TLS and ALS surveys, resulting in DEMs of different resolution and spatial extension. Those factors are obtained, analyzed and evaluated with DEM-based GIS- and statistical analyses. These include factors that are attributed to catchment topography, such as slope angle, curvature, size, shape as well as topographic channel parameters. Together with factors of land cover/use and lithology those features provide the independent variables for further statistical analyses. With the help of several logistic regressions the likelihoods of influencing topographical and lithological factors and factors of land cover/use leading to debris flow events and those for debris flows to reach the main channel (hillslope-channel connectivity) are computed. First results will be presented at the EGU General Assembly 2016.

Rate of Adverse Events and Healthcare Costs Associated with the Topical Treatment of Rosacea.

PubMed

Williamson, Todd; Kamalakar, Rajesh; Ogbonnaya, Augustina; Zagadailov, Erin A; Eaddy, Michael; Kreilick, Charlie

2017-05-01

Rosacea is a condition more common in women than in men, and in people aged ≥30 years than in younger patients. Adverse events associated with the use of topical medications for rosacea may lead to a lack of treatment adherence. Previous studies have reported low treatment adherence rates among patients with rosacea. To describe the rate of treatment discontinuation resulting from adverse events and the associated healthcare costs among patients with rosacea who are receiving a topical medication. We conducted a retrospective cohort study of patients diagnosed with rosacea based on International Classification of Diseases, Ninth Revision, Clinical Modification code 695.3 who were newly initiating topical treatment with metronidazole, azelaic acid, sodium sulfacetamide/sulfur, or benzoyl peroxide between January 1, 2009, and September 30, 2013. Patients were identified from the MarketScan Commercial Claims and Encounters database and the Medicare Supplemental database and had to be aged ≥30 years, have continuous coverage with medical and pharmacy benefits ≥12 months before treatment and ≥3 months after treatment inititation, and have no evidence of oral antibiotic use or ocular rosacea during the study period. The 3-month period immediately after the index date (ie, first topical rosacea treatment) was defined as the postindex period and was used to evaluate the outcome measures, which included the rate of adverse events, treatment patterns, and healthcare costs. The final cohort included 49,351 patients, with a mean age of 54 years, and 74.5% of the patients were female. Metronidazole was the most common (72.7%) treatment, followed by azelaic acid (21.7%), sodium sulfacetamide/sulfur (3.4%), and benzoyl peroxide (2.2%). A total of 6270 (12.7%) patients had a coded adverse event, of whom 199 (3.2%) continued treatment despite the adverse event, 466 (7.4%) switched to another treatment within 8.8 days, and 5605 (89.4%) discontinued therapy within 31.1 days. Patients with adverse events incurred, on average, a cost of $325 (medical, $143; pharmacy, $182) in rosacea-related costs; patients without adverse events incurred, on average, a cost of $172 (medical, $14; pharmacy, $157) in rosacea-related costs. The majority of adverse events associated with current topical drugs for rosacea resulted in treatment switch or discontinuation. Drugs with a different mechanism of action or new formulations of existing drugs may provide additional treatment options for patients and may lead to improved adherence and better symptom control.

Joint probabilistic determination of earthquake location and velocity structure: application to local and regional events

NASA Astrophysics Data System (ADS)

Beucler, E.; Haugmard, M.; Mocquet, A.

2016-12-01

The most widely used inversion schemes to locate earthquakes are based on iterative linearized least-squares algorithms and using an a priori knowledge of the propagation medium. When a small amount of observations is available for moderate events for instance, these methods may lead to large trade-offs between outputs and both the velocity model and the initial set of hypocentral parameters. We present a joint structure-source determination approach using Bayesian inferences. Monte-Carlo continuous samplings, using Markov chains, generate models within a broad range of parameters, distributed according to the unknown posterior distributions. The non-linear exploration of both the seismic structure (velocity and thickness) and the source parameters relies on a fast forward problem using 1-D travel time computations. The a posteriori covariances between parameters (hypocentre depth, origin time and seismic structure among others) are computed and explicitly documented. This method manages to decrease the influence of the surrounding seismic network geometry (sparse and/or azimuthally inhomogeneous) and a too constrained velocity structure by inferring realistic distributions on hypocentral parameters. Our algorithm is successfully used to accurately locate events of the Armorican Massif (western France), which is characterized by moderate and apparently diffuse local seismicity.

Eruption of a Multiple-Turn Helical Magnetic Flux Tube in a Large Flare: Evidence for External and Internal Reconnection that Fits the Breakout Model of Solar Magnetic Eruptions

NASA Technical Reports Server (NTRS)

Gary, G. Allen; Moore, R. L.

2003-01-01

We present observations and an interpretation of a unique multiple-turn spiral flux tube eruption from AR10030 on 2002 July 15. The TRACE CIV observations clearly show a flux tube that is helical and that is erupting from within a sheared magnetic field. These observations are interpreted in the context of the breakout model for magnetic field explosions. The initiation of the helix eruption starts 25 seconds after the peak of the flare s strongest impulsive spike of microwave gryosynchrotron radiation early in the flare s explosive phase, implying that the sheared core field is not the site of the initial reconnection. Within the quadrupolar configuration of the active region, the external and internal reconnection sites are identified in each of two consecutive eruptive flares that produce a double CME. The first external breakout reconnection apparently releases an underlying sheared core field and allows it to erupt, leading to internal reconnection in the wake of the erupting helix. This internal reconnection heats the two-ribbon flare and might or might not produce the helix. These events lead to the first CME and are followed by a second breakout that initiates a second and larger halo CME. The strong magnetic shear in the region is associated with rapid proper motion and evolution of the active region. The multiple-turn helix originates from above a sheared-field magnetic inversion line within a filament channel, and starts to erupt only after fast breakout reconnection has started. These observations are counter to the standard flare model and support the breakout model for eruptive flare initiation. However, the observations are compatible with internal reconnection in a sheared magnetic arcade in the formation and eruption of the helix.

Eruption of a Multiple-Turn Helical Magnetic Flux Tube in a Large Flare: Evidence for External and Internal Reconnection that Fits the Breakout Model of Solar Magnetic Eruptions

NASA Technical Reports Server (NTRS)

Gary, G. Allen; Moore, R. L.

2004-01-01

We present observations and an interpretation of a unique multiple-turn spiral flux tube eruption from active region 10030 on 2002 July 15. The TRACE C IV observations clearly show a flux tube that is helical and erupting from within a sheared magnetic field. These observations are interpreted in the context of the breakout model for magnetic field explosions. The initiation of the helix eruption. as determined by a linear backward extrapolation, starts 25 s after the peak of the flare's strongest impulsive spike of microwave gyrosynchrotron radiation early in the flare s explosive phase, implying that the sheared core field is not the site of the initial reconnection. Within the quadrupolar configuration of the active region, the external and internal reconnection sites are identified in each of two consecutive eruptive flares that produce a double coronal mass ejection (CME). The first external breakout reconnection apparently releases an underlying sheared core field and allows it to erupt, leading to internal reconnection in the wake of the erupting helix. This internal reconnection releases the helix and heats the two-ribbon flare. These events lead to the first CME and are followed by a second breakout that initiates a second and larger halo CME. The strong magnetic shear in the region is compatible with the observed rapid proper motion and evolution of the active region. The multiple-turn helix originates from above a sheared-field magnetic inversion line within a filament channel. and starts to erupt only after fast breakout reconnection has started. These observations are counter to the standard flare model and support the breakout model for eruptive flare initiation.

GR@PPA 2.8: Initial-state jet matching for weak-boson production processes at hadron collisions

NASA Astrophysics Data System (ADS)

Odaka, Shigeru; Kurihara, Yoshimasa

2012-04-01

The initial-state jet matching method introduced in our previous studies has been applied to the event generation of single W and Z production processes and diboson (WW, WZ and ZZ) production processes at hadron collisions in the framework of the GR@PPA event generator. The generated events reproduce the transverse momentum spectra of weak bosons continuously in the entire kinematical region. The matrix elements (ME) for hard interactions are still at the tree level. As in previous versions, the decays of weak bosons are included in the matrix elements. Therefore, spin correlations and phase-space effects in the decay of weak bosons are exact at the tree level. The program package includes custom-made parton shower programs as well as ME-based hard interaction generators in order to achieve self-consistent jet matching. The generated events can be passed to general-purpose event generators to make the simulation proceed down to the hadron level. Catalogue identifier: ADRH_v3_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADRH_v3_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 112 146 No. of bytes in distributed program, including test data, etc.: 596 667 Distribution format: tar.gz Programming language: Fortran; with some included libraries coded in C and C++ Computer: All Operating system: Any UNIX-like system RAM: 1.6 Mega bytes at minimum Classification: 11.2 Catalogue identifier of previous version: ADRH_v2_0 Journal reference of previous version: Comput. Phys. Comm. 175 (2006) 665 External routines: Bash and Perl for the setup, and CERNLIB, ROOT, LHAPDF, PYTHIA according to the user's choice. Does the new version supersede the previous version?: No, this version supports only a part of the processes included in the previous versions. Nature of problem: We need to combine those processes including 0 jet and 1 jet in the matrix elements using an appropriate matching method, in order to simulate weak-boson production processes in the entire kinematical region. Solution method: The leading logarithmic components to be included in parton distribution functions and parton showers are subtracted from 1-jet matrix elements. Custom-made parton shower programs are provided to ensure satisfactory performance of the matching method. Reasons for new version: An initial-state jet matching method has been implemented. Summary of revisions: Weak-boson production processes associated with 0 jet and 1 jet can be consistently merged using the matching method. Restrictions: The built-in parton showers are not compatible with the PYTHIA new PS and the HERWIG PS. Unusual features: A large number of particles may be produced by the parton showers and passed to general-purpose event generators. Running time: About 10 min for initialization plus 25 s for every 1k-event generation for W production in the LHC condition, on a 3.0-GHz Intel Xeon processor with the default setting.

Distribution and Variability of Satellite-Derived Signals of Isolated Convection Initiation Events Over Central Eastern China

NASA Astrophysics Data System (ADS)

Huang, Yipeng; Meng, Zhiyong; Li, Jing; Li, Wanbiao; Bai, Lanqiang; Zhang, Murong; Wang, Xi

2017-11-01

This study combined measurements from the Chinese operational geostationary satellite Fengyun-2E (FY-2E) and ground-based weather radars to conduct a statistical survey of isolated convection initiation (CI) over central eastern China (CEC). The convective environment in CEC is modulated by the complex topography and monsoon climate. From May to August 2010, a total of 1,630 isolated CI signals were derived from FY-2E using a semiautomated method. The formation of these satellite-derived CI signals peaks in the early afternoon and occurs with high frequency in areas with remarkable terrain inhomogeneity (e.g., mountain, water, and mountain-water areas). The high signal frequency areas shift from northwest CEC (dry, high altitude) in early summer to southeast CEC (humid, low altitude) in midsummer along with an increasing monthly mean frequency. The satellite-derived CI signals tend to have longer lead times (the time difference between satellite-derived signal formation and radar-based CI) in the late morning and afternoon than in the early morning and night. During the early morning and night, the distinction between cloud top signatures and background terrestrial radiation becomes less apparent, resulting in delayed identification of the signals and thus short and even negative lead times. A decline in the lead time is observed from May to August, likely due to the increasing cloud growth rate and warm-rain processes. Results show increasing lead times with increasing landscape elevation, likely due to more warm-rain processes over the coastal sea and plain, along with a decreasing cloud growth rate from hill and mountain to the plateau.

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

PubMed Central

Evenepoel, Pieter; Curzi, Mario P.; González, Maria Teresa; Husserl, Fred E.; Kopyt, Nelson; Sterling, Lulu Ren; Mix, Chris; Wong, Gordon

2009-01-01

Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited. Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180. Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were ≤300 pg/ml (weeks 16 through 180) and median Ca×P values were ≤55 mg2/dl2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events. Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. PMID:19696213

Corruption of homeostatic mechanisms in the guanylyl cyclase C signaling pathway underlying colorectal tumorigenesis

PubMed Central

Waldman, Scott A

2010-01-01

Colon cancer, the second leading cause of cancer-related mortality worldwide, originates from the malignant transformation of intestinal epithelial cells. The intestinal epithelium undergoes a highly organized process of rapid regeneration along the crypt-villus axis, characterized by proliferation, migration, differentiation and apoptosis, whose coordination is essential to maintaining the mucosal barrier. Disruption of these homeostatic processes predisposes cells to mutations in tumor suppressors or oncogenes, whose dysfunction provides transformed cells an evolutionary growth advantage. While sequences of genetic mutations at different stages along the neoplastic continuum have been established, little is known of the events initiating tumorigenesis prior to adenomatous polyposis coli (APC) mutations. Here, we examine a role for the corruption of homeostasis induced by silencing novel tumor suppressors, including the intestine-specific transcription factor CDX2 and its gene target guanylyl cyclase C (GCC), as early events predisposing cells to mutations in APC and other sequential genes that initiate colorectal cancer. CDX2 and GCC maintain homeostatic regeneration in the intestine by restricting cell proliferation, promoting cell maturation and adhesion, regulating cell migration and defending the intestinal barrier and genomic integrity. Elimination of CDX2 or GCC promotes intestinal tumor initiation and growth in aged mice, mice carrying APC mutations or mice exposed to carcinogens. The roles of CDX2 and GCC in suppressing intestinal tumorigenesis, universal disruption in their signaling through silencing of hormones driving GCC, and the uniform overexpression of GCC by tumors underscore the potential value of oral replacement with GCC ligands as targeted prevention and therapy for colorectal cancer. PMID:20592492

Structural Features of Sugars That Trigger or Support Conidial Germination in the Filamentous Fungus Aspergillus niger

PubMed Central

Hayer, Kimran; Stratford, Malcolm

2013-01-01

The asexual spores (conidia) of Aspergillus niger germinate to produce hyphae under appropriate conditions. Germination is initiated by conidial swelling and mobilization of internal carbon and energy stores, followed by polarization and emergence of a hyphal germ tube. The effects of different pyranose sugars, all analogues of d-glucose, on the germination of A. niger conidia were explored, and we define germination as the transition from a dormant conidium into a germling. Within germination, we distinguish two distinct stages, the initial swelling of the conidium and subsequent polarized growth. The stage of conidial swelling requires a germination trigger, which we define as a compound that is sensed by the conidium and which leads to catabolism of d-trehalose and isotropic growth. Sugars that triggered germination and outgrowth included d-glucose, d-mannose, and d-xylose. Sugars that triggered germination but did not support subsequent outgrowth included d-tagatose, d-lyxose, and 2-deoxy-d-glucose. Nontriggering sugars included d-galactose, l-glucose, and d-arabinose. Certain nontriggering sugars, including d-galactose, supported outgrowth if added in the presence of a complementary triggering sugar. This division of functions indicates that sugars are involved in two separate events in germination, triggering and subsequent outgrowth, and the structural features of sugars that support each, both, or none of these events are discussed. We also present data on the uptake of sugars during the germination process and discuss possible mechanisms of triggering in the absence of apparent sugar uptake during the initial swelling of conidia. PMID:23995938

Structural features of sugars that trigger or support conidial germination in the filamentous fungus Aspergillus niger.

PubMed

Hayer, Kimran; Stratford, Malcolm; Archer, David B

2013-11-01

The asexual spores (conidia) of Aspergillus niger germinate to produce hyphae under appropriate conditions. Germination is initiated by conidial swelling and mobilization of internal carbon and energy stores, followed by polarization and emergence of a hyphal germ tube. The effects of different pyranose sugars, all analogues of d-glucose, on the germination of A. niger conidia were explored, and we define germination as the transition from a dormant conidium into a germling. Within germination, we distinguish two distinct stages, the initial swelling of the conidium and subsequent polarized growth. The stage of conidial swelling requires a germination trigger, which we define as a compound that is sensed by the conidium and which leads to catabolism of d-trehalose and isotropic growth. Sugars that triggered germination and outgrowth included d-glucose, d-mannose, and d-xylose. Sugars that triggered germination but did not support subsequent outgrowth included d-tagatose, d-lyxose, and 2-deoxy-d-glucose. Nontriggering sugars included d-galactose, l-glucose, and d-arabinose. Certain nontriggering sugars, including d-galactose, supported outgrowth if added in the presence of a complementary triggering sugar. This division of functions indicates that sugars are involved in two separate events in germination, triggering and subsequent outgrowth, and the structural features of sugars that support each, both, or none of these events are discussed. We also present data on the uptake of sugars during the germination process and discuss possible mechanisms of triggering in the absence of apparent sugar uptake during the initial swelling of conidia.

Evolution of an Interfacial Crack on the Concrete Embankment Boundary

NASA Astrophysics Data System (ADS)

Smith, J.; Ezzedine, S. M.; Lomov, I.; Kanarska, Y.; Antoun, T.; Glascoe, L. G.; Hall, R. L.; Woodson, S. C.

2013-12-01

Failure of a dam can have subtle beginnings: a small crack or dislocation at the interface of the concrete dam and the surrounding embankment soil initiated by a seismic event, for example, can: a) result in creating gaps between the concrete dam and the lateral embankments; b) initiate internal erosion of embankment; and c) lead to a catastrophic failure of the dam. The dam may ';self-rehabilitate' if a properly designed granular filter is engineered around the embankment. Currently, the design criteria for such filters have only been based on experimental studies. We demonstrate the numerical prediction of filter effectiveness at the soil grain scale and relate it to the larger dam scale. Validated computer predictions highlight that a resilient (or durable) filter is consistent with the current design specifications for dam filters. These predictive simulations, unlike the design specifications, can be used to assess filter success or failure under different soil or loading conditions and can lead to meaningful estimates of the timing and nature of full-scale dam failure. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344 and was sponsored by the Department of Homeland Security (DHS), Science and Technology Directorate, Homeland Security Advanced Research Projects Agency (HSARPA).

Extreme Weather and Climate: Workshop Report

NASA Technical Reports Server (NTRS)

Sobel, Adam; Camargo, Suzana; Debucquoy, Wim; Deodatis, George; Gerrard, Michael; Hall, Timothy; Hallman, Robert; Keenan, Jesse; Lall, Upmanu; Levy, Marc;

Diagnostic work-up for detection of paroxysmal atrial fibrillation after acute ischemic stroke: cross-sectional survey on German stroke units.

PubMed

Rizos, Timolaos; Quilitzsch, Anika; Busse, Otto; Haeusler, Karl Georg; Endres, Matthias; Heuschmann, Peter; Veltkamp, Roland

2015-06-01

Multiple methods to detect paroxysmal atrial fibrillation (pAF) in patients with acute stroke are available. However, it is unknown which approaches are currently used in clinical routine and guidelines remain vague to the extent of cardiac monitoring. We characterize diagnostic efforts for pAF detection on German stroke units (SU). A standardized anonymous questionnaire was sent to all clinical leads of certified SUs in Germany. The questionnaire focused on basic characteristics of SUs, procedures to detect AF, and estimates on AF detection. One hundred seventy-nine SU leads participated (response rate 71.6%). All patients undergo continuous bedside ECG monitoring. A percentage of 77.6 SUs initiate additional 24-hour Holter ECG in >50% of patients without known AF. Patients with transient ischemic attack are monitored significantly shorter than patients with ischemic stroke. Independent of SU type or size, 67.6% of leads assumed to fail detecting pAF in 5% to 20% of patients. In cryptogenic stroke, additional ECG monitoring is recommended by 90.2% but only 13.8% of SUs perform routine ECG follow-up visits. The use of implanted event recorders is low (1-10 patients/y by 60.7% of SUs; 28.1%: no use). A percentage of 83.9 do not use external event recorders. Our survey demonstrates substantial heterogeneity among German SUs on diagnostic work-up for pAF. Future prospective multicenter studies should systematically evaluate the impact of different methods to uncover pAF. © 2015 American Heart Association, Inc.

HEADWAY TIME AND CRASHES AMONG NOVICE TEENS AND EXPERIENCED ADULT DRIVERS IN A SIMULATED LEAD TRUCK BRAKING SCENARIO

PubMed Central

McDonald, Catherine C.; Seacrist, Thomas S.; Lee, Yi-Ching; Loeb, Helen; Kandadai, Venk; Winston, Flaura K.

2014-01-01

Summary Driving simulators can be used to evaluate driving performance under controlled, safe conditions. Teen drivers are at particular risk for motor vehicle crashes and simulated driving can provide important information on performance. We developed a new simulator protocol, the Simulated Driving Assessment (SDA), with the goal of providing a new tool for driver assessment and a common outcome measure for evaluation of training programs. As an initial effort to examine the validity of the SDA to differentiate performance according to experience, this analysis compared driving behaviors and crashes between novice teens (n=20) and experienced adults (n=17) on a high fidelity simulator for one common crash scenario, a rear-end crash. We examined headway time and crashes during a lead truck with sudden braking event in our SDA. We found that 35% of the novice teens crashed and none of the experienced adults crashed in this lead truck braking event; 50% of the teens versus 25% of the adults had a headway time <3 seconds at the time of truck braking. Among the 10 teens with <3 seconds headway time, 70% crashed. Among all participants with a headway time of 2–3 seconds, further investigation revealed descriptive differences in throttle position and brake pedal force when comparing teens who crashed, teens who did not crash and adults (none of whom crashed). Even with a relatively small sample, we found statistically significant differences in headway time for adults and teens, providing preliminary construct validation for our new SDA. PMID:25197724

Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

PubMed

Mugavero, Michael J; May, Margaret; Harris, Ross; Saag, Michael S; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F; Dabis, Francois; Hogg, Robert; de Wolf, Frank; Fatkenheuer, Gerd; Gill, M John; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M; Staszewski, Schlomo; Sterne, Jonathan A C

2008-11-30

To determine whether differences in short-term virologic failure among commonly used antiretroviral therapy (ART) regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Observational cohort study of patients initiating ART between January 2000 and December 2005. The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. A total of 13 546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz, nevirapine, lopinavir/ritonavir, nelfinavir, or abacavir as third drugs in combination with a zidovudine and lamivudine nucleoside reverse transcriptase inhibitor backbone. Short-term (24-week) virologic failure (>500 copies/ml) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Compared with efavirenz as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; nevirapine (adjusted odds ratio = 1.87, 95% confidence interval (CI) = 1.58-2.22), lopinavir/ritonavir (1.32, 95% CI = 1.12-1.57), nelfinavir (3.20, 95% CI = 2.74-3.74), and abacavir (2.13, 95% CI = 1.82-2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with nevirapine (adjusted hazard ratio for composite outcome measure 1.27, 95% CI = 1.04-1.56) and abacavir (1.22, 95% CI = 1.00-1.48). Among antiretroviral-naïve patients initiating therapy, between-ART regimen, differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication.

Effect of Promotional Initiatives on Visits to a Dedicated Website for Physical Activity and Non-Communicable Disease in Luxembourg: An Event Study

PubMed Central

Lion, Alexis; Thornton, Jane S.; Vaillant, Michel; Pertuy, Juliette; Besenius, Eric; Hardy, Cyrille; Delagardelle, Charles; Seil, Romain; Urhausen, Axel; Theisen, Daniel

2017-01-01

The Sport-Santé project and its website (www.sport-sante.lu) promote physical activity for individuals with non-communicable diseases (NCDs) in Luxembourg. Our purpose was to perform an event study analysis to evaluate the effects of communication and promotional initiatives on the number of visits to the Sport-Santé website. Between September 2015 and May 2016, the Sport-Santé website was promoted during different initiatives, including participation in health-related events or publication of articles in local journals. The daily number of visits to www.sport-sante.lu website (i.e., our outcome) was recorded using Google Analytics and compared to a counterfactual collected with its benchmarking tool. The counterfactual was defined as the daily number of visits to websites in the same field. A model was created to evaluate the relationship between the number of visits to www.sport-sante.lu website and the number of visits to similar websites during a control period with no promotional initiatives (from July 2015 to September 2015). The effect of promotional initiatives was subsequently tested, by comparing the actual number of visits to our website (up to 2 days after each event) with the theoretical number of visits predicted by the model. Twenty-two initiatives were identified, of which 11 were participations at major health-related events and 11 publications of popular science articles. Of these 22 initiatives, the event study identified 2 popular science articles and 1 interactive workshop that significantly increased the daily number of visits to the www.sport-sante.lu website. One of the two articles was published on the day before the workshop was held, which did not allow us to distinguish its specific impact. The second article was published in the main national newspaper. This is the first time to our knowledge that an event study analysis has been used to evaluate the impact of promotional initiatives on the number of visits to a dedicated website for physical activity and NCDs. Our results indicate that some initiatives can aid in the number of visits, but in general their impact is limited. To observe an increased rate of participation in physical activity, additional promotional and evaluative strategies should be explored. PMID:28611975

Behavior of lead in pristine and urbanized acid wetlands in the New Jersey pinelands with special reference to the role of Sphagnum moss

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vedagiri, U.K.

1989-01-01

The purpose of this study was to investigate the behavior of lead in naturally acidic Sphagnum moss-dominated wetlands of the New Jersey Pinelands and to compare it to the behavior of lead in similar wetlands which had been impacted by storm-water runoff. Data from the field showed that the runoff-impacted sites were characterized by elevated pH, elimination of Spaghnum ground cover, erosion of peat substrate and high lead accumulations, contributing to an effective but decreasing sink capacity. Laboratory experiments explored differences in fractionation, mobility and bioavailability of lead between the two systems. The low pH and high dissolved organic mattermore » of the pristine waters led to higher solubilization and complexing of added lead compared to impacted waters. Lead added to runoff showed unexpectedly high solubility and lability, possibly due to low suspended solids. Lead added to runoff was also much more mobile vertically through peat columns than lead added to swampwater, possibly due to its high lability. The extremely high porosity of the peat substrate allows rapid vertical migration of solutes during events of sudden influx, such as storms. Sphagnum moss greatly decreased vertical transport by binding and flow retardation. The lead that is held in the moss layer was differentially available to different species. Red maple seedlings were better able to take up lead from the peat substrate in the absence of moss cover while cranberry plants showed the reverse pattern. This may be related to differences in rooting requirements and growth of the two species. Lead added in runoff was initially less available to the plants than in swampwater, but was ultimately taken up the red maple, which could tolerate conditions in the impacted substrates.« less

Triggering Mechanism for Neutron Induced Single-Event Burnout in Power Devices

NASA Astrophysics Data System (ADS)

Shoji, Tomoyuki; Nishida, Shuichi; Hamada, Kimimori

2013-04-01

Cosmic ray neutrons can trigger catastrophic failures in power devices. It has been reported that parasitic transistor action causes single-event burnout (SEB) in power metal-oxide-semiconductor field-effect transistors (MOSFETs) and insulated gate bipolar transistors (IGBTs). However, power diodes do not have an inherent parasitic transistor. In this paper, we describe the mechanism triggering SEB in power diodes for the first time using transient device simulation. Initially, generated electron-hole pairs created by incident recoil ions generate transient current, which increases the electron density in the vicinity of the n-/n+ boundary. The space charge effect of the carriers leads to an increase in the strength of the electric field at the n-/n+ boundary. Finally, the onset of impact ionization at the n-/n+ boundary can trigger SEB. Furthermore, this failure is closely related to diode secondary breakdown. It was clarified that the impact ionization at the n-/n+ boundary is a key point of the mechanism triggering SEB in power devices.

Non-suicidal self-injury and firesetting: shared and unique correlates among school-based adolescents.

PubMed

Tanner, Alicia K; Hasking, Penelope; Martin, Graham

2015-04-01

Distinct behaviors such as non-suicidal self-injury (NSSI) and firesetting may represent functionally equivalent attempts to regulate difficult affective/cognitive or social experiences during adolescence. This study examined possible mechanisms leading to NSSI, as opposed to firesetting, as well as co-occurrence of these behaviors. Participants aged 12-18 years (N = 2,356; 67.5 % female) completed self-report questionnaires measuring NSSI and firesetting, as well as socio-demographic and psychosocial factors including personality traits related to impulsivity and anxiety, negative life events, emotion regulation, and coping. The findings indicated the presence of general risk factors (e.g., negative life events and poor coping) that increase the likelihood that adolescents will engage in any of a range of maladaptive behaviors. The probability of at-risk adolescents engaging in NSSI was increased by psychological states (i.e., rumination and poor self-esteem), whereas socio-demographic and personality traits were associated with firesetting. Implications for prevention and early intervention initiatives are discussed.

Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

PubMed

Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

2018-04-01

Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

Case of mumps orchitis after vaccination.

PubMed

Kanda, Takayoshi; Mochida, Junichi; Takada, Shogo; Hori, Yutaro; Yamaguchi, Kenya; Takahashi, Satoru

2014-04-01

We present a case of mumps orchitis after vaccination. A 35-year-old man visited the emergency unit of our hospital for fever and right testicular pain on 7 January 2012. Two weeks before the visit, he underwent vaccination for mumps. After 7 days of hospitalization, the patient recovered from fever and testicular pain. Scrotal magnetic resonance imaging suggested right orchitis, and an increased level of serum mumps immunoglobulin M and immunoglobulin G indicated an initial infection of mumps virus. The peak value of immunoglobulin G showed 106 enzyme immunoassay unit 5 weeks after vaccination, which was 10-fold higher than the ordinary rise of a vaccinated individual. This fact leads to two possibilities. One is this happened as an adverse event of vaccination, and the other is that he actually had a wild-type infection at the same time as vaccination. There are some reports regarding adverse events of mumps vaccine; however, they might include wild-type infection. © 2013 The Japanese Urological Association.

Non-flow correlations and elliptic flow fluctuations in Au+Au collisions at sNN=200 GeV

NASA Astrophysics Data System (ADS)

Alver, B.; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Halliwell, C.; Hamblen, J.; Hauer, M.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Hołyński, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kulinich, P.; Kuo, C. M.; Li, W.; Lin, W. T.; Loizides, C.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Reed, C.; Roland, C.; Roland, G.; Sagerer, J.; Seals, H.; Sedykh, I.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Walters, P.; Wenger, E.; Wolfs, F. L. H.; Wosiek, B.; Woźniak, K.; Wysłouch, B.

2010-03-01

This article presents results on event-by-event elliptic flow fluctuations in Au+Au collisions at sNN= 200 GeV, where the contribution from non-flow correlations has been subtracted. An analysis method is introduced to measure non-flow correlations, relying on the assumption that non-flow correlations are most prominent at short ranges (|Δη|<2). Assuming that non-flow correlations are of the order that is observed in p+p collisions for long-range correlations (|Δη|>2), relative elliptic flow fluctuations of approximately 30-40% are observed. These results are consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. It is found that the long-range non-flow correlations in Au+Au collisions would have to be more than an order of magnitude stronger compared to the p+p data to lead to the observed azimuthal anisotropy fluctuations with no intrinsic elliptic flow fluctuations.

A basal thunnosaurian from Iraq reveals disparate phylogenetic origins for Cretaceous ichthyosaurs

PubMed Central

Fischer, Valentin; Appleby, Robert M.; Naish, Darren; Liston, Jeff; Riding, James B.; Brindley, Stephen; Godefroit, Pascal

2013-01-01

Cretaceous ichthyosaurs have typically been considered a small, homogeneous assemblage sharing a common Late Jurassic ancestor. Their low diversity and disparity have been interpreted as indicative of a decline leading to their Cenomanian extinction. We describe the first post-Triassic ichthyosaur from the Middle East, Malawania anachronus gen. et sp. nov. from the Early Cretaceous of Iraq, and re-evaluate the evolutionary history of parvipelvian ichthyosaurs via phylogenetic and cladogenesis rate analyses. Malawania represents a basal grade in thunnosaurian evolution that arose during a major Late Triassic radiation event and was previously thought to have gone extinct during the Early Jurassic. Its pectoral morphology appears surprisingly archaic, retaining a forefin architecture similar to that of its Early Jurassic relatives. After the initial latest Triassic radiation of early thunnosaurians, two subsequent large radiations produced lineages with Cretaceous representatives, but the radiation events themselves are pre-Cretaceous. Cretaceous ichthyosaurs therefore include distantly related lineages, with contrasting evolutionary histories, and appear more diverse and disparate than previously supposed. PMID:23676653

Study of radioactive impurities in neutron transmutation doped germanium

NASA Astrophysics Data System (ADS)

Mathimalar, S.; Dokania, N.; Singh, V.; Nanal, V.; Pillay, R. G.; Shrivastava, A.; Jagadeesan, K. C.; Thakare, S. V.

2015-02-01

A program to develop low temperature (mK) sensors with neutron transmutation doped Ge for rare event studies with a cryogenic bolometer has been initiated. For this purpose, semiconductor grade Ge wafers are irradiated with thermal neutron flux from Dhruva reactor at Bhabha Atomic Research Centre (BARC), Mumbai. Spectroscopic studies of irradiated samples have revealed that the environment of the capsule used for irradiating the sample leads to significant levels of 65Zn, 110mAg and 182Ta impurities, which can be reduced by chemical etching of approximately 50 μm thick surface layer. From measurements of the etched samples in the low background counting setup, activity due to trace impurities of 123Sb in bulk Ge is estimated to be 1 Bq / g after irradiation. These estimates indicate that in order to use the NTD Ge sensors for rare event studies, a cooldown period of 2 years would be necessary to reduce the radioactive background to ≤ 1 mBq / g.

Computations of Vertical Displacement Events with Toroidal Asymmetry

NASA Astrophysics Data System (ADS)

Sovinec, C. R.; Bunkers, K. J.

2017-10-01

Nonlinear numerical MHD modeling with the NIMROD code [https://nimrodteam.org] is being developed to investigate asymmetry during vertical displacement events. We start from idealized up/down symmetric tokamak equilibria with small levels of imposed toroidally asymmetric field errors. Vertical displacement results when removing current from one of the two divertor coils. The Eulerian reference-frame modeling uses temperature-dependent resistivity and anisotropic thermal conduction to distinguish the hot plasma region from surrounding cold, low-density conditions. Diffusion through a resistive wall is slow relative to Alfvenic scales but much faster than resistive plasma diffusion. Loss of the initial edge pressure and current distributions leads to a narrow layer of parallel current, which drives low-n modes that may be related to peeling-dominated ELMs. These modes induce toroidal asymmetry in the conduction current, which connects the simulated plasma to the wall. Work supported by the US DOE through Grant Numbers DE-FG02-06ER54850 and DE-FC02-08ER54975.

A missed penalty kick triggered coronary death in the husband and broken heart syndrome in the wife.

PubMed

Y-Hassan, Shams; Feldt, Kari; Stålberg, Marcus

2015-11-15

Events that induce emotional stress and frustration in a large number of subjects under specific circumstances, such as earthquakes, war conditions, and sporting occasions, may increase the incidence of cardiovascular events, such as acute myocardial infarction, arrhythmias, and sudden cardiac death. This report describes a married couple who expressed an apparently passionate interest in football with hazardous consequences after a tense football match during the FIFA 2014 World Championships. A series of emotional stressors initiated by defeat in this football game lead to cardiac arrest in a 58-year-old man caused by a thrombotic occlusion of the left anterior descending artery and ending in the death of the patient. An hour and 15 minutes after the onset of cardiac arrest of the patient, his 64-year-old wife also had chest pain caused by an acute midventricular takotsubo syndrome. She survived the acute stage of the disease, and there was complete resolution of the left ventricular dysfunction. Copyright © 2015 Elsevier Inc. All rights reserved.

Soil erosion transport through multiple rainfall events in the presence of stone cover: Laboratory flume experiments and analysis with the Hairsine-Rose model

NASA Astrophysics Data System (ADS)

Jomaa, S.; Barry, D. A.; Brovelli, A.; Heng, B. P.; Sander, G. C.; Parlange, J.

2011-12-01

Soil erosion is a major environmental problem that can lead to loss of fertility and degradation of agricultural fields. In order to develop efficient strategies to mitigate the impact of precipitation and reduce the erosion rate, a process-based understanding of the mechanisms that govern sediment transport and delivery is necessary. Soil state and physical properties prior to a precipitation event can affect significantly the erosion rate. Among the most important soil variables are moisture content, compaction and infiltration capacity. Additionally, the presence of stones on the topsoil surface retards the overland flow discharge, reduces runoff generation as well as the sediment delivery and prevents the development of a surface seal, which in turn maintains the infiltration rate. The aim of this study was to examine in detail the effect of surface stones, soil compaction and sealing for a sequence of rainfall events on soil erosion. Experiments were conducted using the EPFL erosion flume, which was divided into two identical flumes (one with stone and one without). The experiment involved four rainfall events with the precipitation rates: 28, 74, 74 and 28 mm h-1. After each 2-h event, the soil was allowed to air dry for 22 h. The total sediment concentration, the concentration of seven sediment size classes and the flow discharge were measured during each event at the outlet of each flume. Experimental results were analyzed using the Hairsine and Rose (H-R) soil erosion model. Results showed that (i) within each precipitation event, the proportion of each size class for the bare/stone-covered flume pairs at steady state were similar, whereas the initial response differed significantly; (ii) in all cases the effluent was enriched in finer particles relative to the original soil; and (iii) the effluent sediment composition was different from that of the original soil, and there was no clear trend towards the parent soil sediment size composition with time. The H-R model was able to reproduce well the events with high precipitation rate (events 2 and 3) with the same parameter set, while the match was less satisfactory for the low precipitation events. A possible explanation for this is that the initial soil compaction/sealing/development of the deposited layer combined to yield a surface that eroded similarly for identical rainfall conditions. Changes in the precipitation rate modifies the soil surface (the deposited layer in particular) and thus the erosion rates. Model application further suggested that over the course of the rainfall events, the contribution of the original soil to the eroded sediment decreased gradually, while that of the deposited layer increased.

Rupture characteristics of the three M ∼ 4.7 (1992-1994) Parkfield earthquakes

USGS Publications Warehouse

Fletcher, Jon Peter B.; Spudich, Paul A.

1998-01-01

Slip on the San Andreas fault was determined for three M ∼ 4.7 earthquakes using a tomographic inverse system [Beroza and Spudich, 1988] to invert seismic source time functions (STFs) from S waves. STFs were obtained by deconvolving mainshock accelerograms by those from collocated smaller earthquakes. Accelerograms were from the U.S. Geological Survey Parkfield Small Aperture Array (UPSAR) and from a distributed array of digital accelerometer stations at Parkfield. Eight or nine STFs are used in each of the three inversions. STFs are typically symmetrical pulses with a duration of about 0.3–0.5 s. In the inversion, mainshock rise time was set to 0.05 s, and we allowed the rupture time to vary slightly from a constant rupture velocity of approximately 0.85β. Rupture for all three events, which are located in or close to the Middle Mountain preparation zone or box (MMB), quickly reaches a local maximum in slip and then propagates outward to peaks, ridges, or plateaus in the slip distribution. Slip for the October 20, 1992, event (located just inside the southern edge of the MMB) propagates from an initial spike north and updip along a curving ridge for about 2 km. The initial spike continued to grow in the November 14, 1993, event (located north of the October 20, 1992, event just beneath the hypocenter of the 1966 Parkfield earthquake), which shows little directivity, although there is a smaller patch of slip updip and to the south. In contrast, rupture for the December 20, 1994, event (located just south of the October 20, 1992, event) propagated north and slightly updip, creating a rough plateau in slip a few kilometers wide on a side. Directivity for this event also is to the north. Directivity for all three events points in the approximate direction of the 1966 hypocenter. Small pulses, which comprise a coda, are found on the STFs for several seconds after the initial impulsive event. Several tests based on the assumption that the average of all STFs from UPSAR for each event is an estimate of the true slip at the source suggest that the codas in the STFs are S waves from a long-duration source rather than uncorrected site response. An initiation phase is found on the array average for the November 14, 1993, and December 20, 1994, events. These precursory phases are the result of a spike in slip at the hypocenter. A value of 2.4–4 mm is obtained for Dc, the slip-weakening distance, by interpreting the initial spike as a critical patch. The few aftershocks for the October 20, 1992, event are distributed to the north and updip of the mainshock, but the November 14, 1993, event had a strong burst of aftershock activity that propagated to the north of its hypocenter at roughly the same depth. Aftershocks of the December 20, 1994, event are mostly updip. The November 14, 1993, event had the simplest slip distribution, appeared to be the most impulsive, and had the most active aftershock sequence and the greatest depth. If the eventual Parkfield earthquake initiates near the 1966 hypocenter, then the directivity of the three events studied here will have pointed to it. However, it is certainly possible that both the initiation of characteristic Parkfield shocks and the directivity of smaller events are controlled by fault properties on a larger scale such as by fault bends or jogs.

Geomorphologically effective floods from moraine-dammed lakes in the Cordillera Blanca, Peru

NASA Astrophysics Data System (ADS)

Emmer, Adam

2017-12-01

Outburst floods originating in moraine-dammed lakes represent a significant geomorphological process as well as a specific type of threat for local communities in the Cordillera Blanca, Peru (8.5°-10° S; 77°-78° W). An exceptional concentration of catastrophic floods has been reported from the Cordillera Blanca in the first half of 20th Century (1930s-1950s), leading to thousands of fatalities. The main objective of this paper is to provide a revised and comprehensive overview of geomorphologically effective floods in the area of interest, using various documentary data sources, verified by analysis of remotely sensed images (1948-2013) and enhanced by original field data. Verified events (n = 28; 4 not mentioned before) are analysed from the perspective of spatiotemporal distribution, pre-flood conditions, causes, mechanisms and geomorphological impacts as well as socioeconomical consequences, revealing certain patterns and similar features. GLOFs are further classified according to their magnitude: 5 extreme events, 8 major events and 15 minor events are distinguished, referring to the quantified geomorphological and socioeconomical impacts. Selected moraine dams and flood deposits are dated using lichenometric dating. Special attention is given to moraine dam breaches - the most frequent type of water release with the most significant consequences. Selected major events and their consequences are studied in detail in a separate section. Finally, a general schematic model of lake formation, growth and post-flood evolution reflecting initial topographical setting and glacier retreat is introduced and the utilization of the obtained results is outlined.

High frequency new particle formation in the Himalayas

PubMed Central

Venzac, Hervé; Sellegri, Karine; Laj, Paolo; Villani, Paolo; Bonasoni, Paolo; Marinoni, Angela; Cristofanelli, Paolo; Calzolari, Francescopiero; Fuzzi, Sandro; Decesari, Stefano; Facchini, Maria-Cristina; Vuillermoz, Elisa; Verza, Gian Pietro

2008-01-01

Rising air pollution levels in South Asia will have worldwide environmental consequences. Transport of pollutants from the densely populated regions of India, Pakistan, China, and Nepal to the Himalayas may lead to substantial radiative forcing in South Asia with potential effects on the monsoon circulation and, hence, on regional climate and hydrological cycles, as well as to dramatic impacts on glacier retreat. An improved description of particulate sources is needed to constrain the simulation of future regional climate changes. Here, the first evidence of very frequent new particle formation events occurring up to high altitudes is presented. A 16-month record of aerosol size distribution from the Nepal Climate Observatory at Pyramid (Nepal, 5,079 m above sea level), the highest atmospheric research station, is shown. Aerosol concentrations are driven by intense ultrafine particle events occurring on >35% of the days at the interface between clean tropospheric air and the more polluted air rising from the valleys. During a pilot study, we observed a significant increase of ion cluster concentrations with the onset of new particle formation events. The ion clusters rapidly grew to a 10-nm size within a few hours, confirming, thus, that in situ nucleation takes place up to high altitudes. The initiation of the new particle events coincides with the shift from free tropospheric downslope winds to thermal upslope winds from the valley in the morning hours. The new particle formation events represent a very significant additional source of particles possibly injected into the free troposphere by thermal winds. PMID:18852453

Application of the aviation black box principle in pediatric cardiac surgery: tracking all failures in the pediatric cardiac operating room.

PubMed

Bowermaster, Rebecca; Miller, Megan; Ashcraft, Traci; Boyd, Michael; Brar, Anoop; Manning, Peter; Eghtesady, Pirooz

2015-02-01

Cardiac surgical procedures are complex and require the coordinated action of many. This creates the potential for small failures that could be the substrate for subsequent morbidity or mortality. High-reliability science suggests that preoccupation with small failures can lead to improved outcomes. Failures of all magnitudes (ie, events) were captured within the pediatric cardiac operating room starting with a single surgeon in April 2008. As the surgical team became more familiar with the process, failure recording was extended to all surgeons and all surgical procedures performed until the conclusion of the study in December 2010. New recording processes were developed and used on a rolling basis during this study. With systematic capture, event rates increased (from occurring within 20% to 50% of operative procedures). Although we identified 9 recurrent patterns, 2 categories (ie, Equipment and Patient Instability) accounted for almost half of the events (45%). The greatest number of events occurred during the prebypass period (40.2%), compared with bypass (20.1%) and postbypass (32.3%) periods. These events were mainly difficulties in access (31.8%), equipment (42.4%), and patient instability (33.3%) in each of the epochs, respectively. Of all events, 7.3% occurred during nonbypass cases, 30.6% of these were communication events. Implementation of this initiative led to recognition of major system-wide issues (eg, need for change in the blood-product acquisition process). Preoccupation with all failures in the operating room can reveal important information about the operating room and perioperative microenvironment that can prompt substantive process changes both locally and within the larger health system. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Could a multi-PeV neutrino event have as origin the internal shocks inside the GRB progenitor star?

NASA Astrophysics Data System (ADS)

Fraija, N.

2016-03-01

The IceCube Collaboration initially reported the detection of 37 extraterrestrial neutrinos in the TeV-PeV energy range. The reconstructed neutrino events were obtained during three consecutive years of data taking, from 2010 to 2013. Although these events have been discussed to have an extragalactic origin, they have not been correlated to any known source. Recently, the IceCube Collaboration reported a neutrino-induced muon event with energy of 2.6 ± 0.3 PeV which corresponds to the highest event ever detected. Neither the reconstructed direction of this event (J2000.0), detected on June 11 2014 at R.A. = 110 ° . 34, Dec. = 11 ° . 48 matches with any familiar source. Long gamma-ray bursts (lGRBs) are usually associated with the core collapse of massive stars leading relativistic-collimated jets inside stars with high-energy neutrino production. These neutrinos have been linked to the 37 events previously detected by IceCube experiment. In this work, we explore the conditions and values of parameters so that the highest neutrino recently detected could be generated by proton-photon and proton-hadron interactions at internal shocks inside lGRB progenitor star and then detected in IceCube experiment. Considering that internal shocks take place in a relativistic collimated jet, whose (half) opening angle is θ0 ∼ 0.1, we found that lGRBs with total luminosity L ≲1048 erg/s and internal shocks on the surface of progenitors such as Wolf-Rayet (WR) and blue super giant (BSG) stars favor this multi-PeV neutrino production, although this neutrino could be associated with L ∼1050.5 (∼1050) erg/s provided that the internal shocks occur at ∼109 (∼1010.2) cm for a WR (BSG).

Whole Genome Sequence Analysis of Mutations Accumulated in rad27Δ Yeast Strains with Defects in the Processing of Okazaki Fragments Indicates Template-Switching Events

PubMed Central

Omer, Sumita; Lavi, Bar; Mieczkowski, Piotr A.; Covo, Shay; Hazkani-Covo, Einat

2017-01-01

Okazaki fragments that are formed during lagging strand DNA synthesis include an initiating primer consisting of both RNA and DNA. The RNA fragment must be removed before the fragments are joined. In Saccharomyces cerevisiae, a key player in this process is the structure-specific flap endonuclease, Rad27p (human homolog FEN1). To obtain a genomic view of the mutational consequence of loss of RAD27, a S. cerevisiae rad27Δ strain was subcultured for 25 generations and sequenced using Illumina paired-end sequencing. Out of the 455 changes observed in 10 colonies isolated the two most common types of events were insertions or deletions (INDELs) in simple sequence repeats (SSRs) and INDELs mediated by short direct repeats. Surprisingly, we also detected a previously neglected class of 21 template-switching events. These events were presumably generated by quasi-palindrome to palindrome correction, as well as palindrome elongation. The formation of these events is best explained by folding back of the stalled nascent strand and resumption of DNA synthesis using the same nascent strand as a template. Evidence of quasi-palindrome to palindrome correction that could be generated by template switching appears also in yeast genome evolution. Out of the 455 events, 55 events appeared in multiple isolates; further analysis indicates that these loci are mutational hotspots. Since Rad27 acts on the lagging strand when the leading strand should not contain any gaps, we propose a mechanism favoring intramolecular strand switching over an intermolecular mechanism. We note that our results open new ways of understanding template switching that occurs during genome instability and evolution. PMID:28974572

Experimental Approaches to Systematic Discovery and Development of Reproductive Adverse Outcome Pathways in Fish

EPA Science Inventory

Adverse outcome pathways (AOPs) are conceptual frameworks that portray causal and predictive linkages between key events at multiple scales of biological organization that connect molecular initiating events and early cellular perturbations (e.g., initiation of toxicity pathways)...

Master Logic Diagram: method for hazard and initiating event identification in process plants.

PubMed

Papazoglou, I A; Aneziris, O N

2003-02-28

Master Logic Diagram (MLD), a method for identifying events initiating accidents in chemical installations, is presented. MLD is a logic diagram that resembles a fault tree but without the formal mathematical properties of the latter. MLD starts with a Top Event "Loss of Containment" and decomposes it into simpler contributing events. A generic MLD has been developed which may be applied to all chemical installations storing toxic and/or flammable substances. The method is exemplified through its application to an ammonia storage facility.

Stochastic events may lead to accretion in Saturn's rings

NASA Astrophysics Data System (ADS)

Esposito, Larry W.

Stochastic events may lead to accretion in Saturn's rings Larry W. Esposito LASP, University of Colorado UVIS occultations indicate accretion is triggered at the B ring edge, in strong density waves in ring A and in the F ring. Moons may trigger accretion by streamline crowding (Lewis & Stewart); which enhances collisions, leading to accretion; increasing random velocities; leading to more collisions and more accretion. Cassini occultations of these strongly perturbed locations show not only accretion but also disaggregation, with time scales of hours to weeks. The collisions may lead to temporary aggregations via stochastic events: collisions can compress unconsolidated objects, trigger adhesion or bring small pieces into contact with larger or higher-density seeds. Disaggregation then can follow from disruptive collisions or tidal shedding. In the accretion/disruption balance, increased random motions could eventually give the upper hand to disruption. . . just as `irrational exuberance' can lead to financial panic in the economy; or the overpopulation of hares can lead to boom-and-bust in the population of foxes. I present a simple predator-prey model. This system's unstable equilibrium can similarly give rise to episodic cycles in accretion: explaining why the observable ring features that indicate embedded objects have been increasing since the beginning of Cassini's observations of Saturn in 2004. Unlike other interpretations of the peculiar events seen near Saturn Equinox, I emphasize the kinetic description of particle interactions rather than a fluid instability approach; and the dominance of stochastic events involving individual aggregates over free and/or driven modes in a flat disk.

The "perfect storm" in compensation: convergence of events leads to a greater need to review compensation strategies.

PubMed

Jones, Robert B

2004-01-01

The recent unprecedented convergence of significant strategic events in the compensation arena has created the need for ongoing and extensive compensation planning. This article reviews the events leading to this point, describes the implications of the results from a recent Aon study with WorldatWork, and suggests what employers can do to successfully navigate the "perfect storm" in compensation.

Does a more skilful meteorological input lead to a more skilful flood forecast at seasonal timescales?

NASA Astrophysics Data System (ADS)

Neumann, Jessica; Arnal, Louise; Magnusson, Linus; Cloke, Hannah

2017-04-01

Seasonal river flow forecasts are important for many aspects of the water sector including flood forecasting, water supply, hydropower generation and navigation. In addition to short term predictions, seasonal forecasts have the potential to realise higher benefits through more optimal and consistent decisions. Their operational use however, remains a challenge due to uncertainties posed by the initial hydrologic conditions (e.g. soil moisture, groundwater levels) and seasonal climate forcings (mainly forecasts of precipitation and temperature), leading to a decrease in skill with increasing lead times. Here we present a stakeholder-led case study for the Thames catchment (UK), currently being undertaken as part of the H2020 IMPREX project. The winter of 2013-14 was the wettest on record in the UK; driven by 12 major Atlantic depressions, the Thames catchment was subject to compound (concurrent) flooding from fluvial and groundwater sources. Focusing on the 2013-14 floods, this study aims to see whether increased skill in meteorological input translates through to more accurate forecasting of compound flood events at seasonal timescales in the Thames catchment. An earlier analysis of the ECMWF System 4 (S4) seasonal meteorological forecasts revealed that it did not skilfully forecast the extreme event of winter 2013-14. This motivated the implementation of an atmospheric experiment by the ECMWF to force the S4 to more accurately represent the low-pressure weather conditions prevailing in winter 2013-14 [1]. Here, we used both the standard and the "improved" S4 seasonal meteorological forecasts to force the EFAS (European Flood Awareness System) LISFLOOD hydrological model. Both hydrological forecasts were started on the 1st of November 2013 and run for 4 months of lead time to capture the peak of the 2013-14 flood event. Comparing the seasonal hydrological forecasts produced with both meteorological forcing data will enable us to assess how the improved meteorology translates into skill in the hydrological forecast for this extreme compound event. As primary stakeholders involved in the study, the Environment Agency and Flood Forecasting Centre are responsible for managing flood risk in the UK. For them, the detection of a potential flood signal weeks or months in advance could be of great value in terms of operational practice, decision-making and early warning. [1] Rodwell, M.J., Ferranti, L., Magnusson, L., Weisheimer, A., Rabier, F. & Richardson, D. (2015) Diagnosis of northern hemispheric regime behaviour during winter 2013/14. ECMWF Technical Memoranda 769.

Processing circuitry for single channel radiation detector

NASA Technical Reports Server (NTRS)

Holland, Samuel D. (Inventor); Delaune, Paul B. (Inventor); Turner, Kathryn M. (Inventor)

2009-01-01

Processing circuitry is provided for a high voltage operated radiation detector. An event detector utilizes a comparator configured to produce an event signal based on a leading edge threshold value. A preferred event detector does not produce another event signal until a trailing edge threshold value is satisfied. The event signal can be utilized for counting the number of particle hits and also for controlling data collection operation for a peak detect circuit and timer. The leading edge threshold value is programmable such that it can be reprogrammed by a remote computer. A digital high voltage control is preferably operable to monitor and adjust high voltage for the detector.

Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the United States

PubMed Central

Hsu, HE; Rydzak, CE; Cotich, KL; Wang, B; Sax, PE; Losina, E; Freedberg, KA; Goldie, SJ; Lu, Z; Walensky, RP

2010-01-01

Objectives We quantified the benefits (life expectancy gains) and harms (efavirenz-related teratogenicity) associated with using efavirenz in HIV-infected women of childbearing age in the United States. Methods We used data from the Women’s Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz-based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor-based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100,000 women, we incorporated literature-based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women. Results Survival for HIV-infected women who received an efavirenz-based initial antiretroviral therapy regimen was 0.89 years greater than for women receiving non-efavirenz-based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100,000 exposed women, compared with 72.46/100,000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS-related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz-exposed women. Conclusions Use of non-efavirenz-based initial antiretroviral therapy in HIV-infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision-making regarding efavirenz use presents a tradeoff between these two risks; this study can inform discussions between patients and health care providers. PMID:20561082

Quantifying the risks and benefits of efavirenz use in HIV-infected women of childbearing age in the USA.

PubMed

Hsu, H E; Rydzak, C E; Cotich, K L; Wang, B; Sax, P E; Losina, E; Freedberg, K A; Goldie, S J; Lu, Z; Walensky, R P

2011-02-01

The aim of the study was to quantify the benefits (life expectancy gains) and risks (efavirenz-related teratogenicity) associated with using efavirenz in HIV-infected women of childbearing age in the USA. We used data from the Women's Interagency HIV Study in an HIV disease simulation model to estimate life expectancy in women who receive an efavirenz-based initial antiretroviral regimen compared with those who delay efavirenz use and receive a boosted protease inhibitor-based initial regimen. To estimate excess risk of teratogenic events with and without efavirenz exposure per 100,000 women, we incorporated literature-based rates of pregnancy, live births, and teratogenic events into a decision analytic model. We assumed a teratogenicity risk of 2.90 events/100 live births in women exposed to efavirenz during pregnancy and 2.68/100 live births in unexposed women. Survival for HIV-infected women who received an efavirenz-based initial antiretroviral therapy (ART) regimen was 0.89 years greater than for women receiving non-efavirenz-based initial therapy (28.91 vs. 28.02 years). The rate of teratogenic events was 77.26/100,000 exposed women, compared with 72.46/100,000 unexposed women. Survival estimates were sensitive to variations in treatment efficacy and AIDS-related mortality. Estimates of excess teratogenic events were most sensitive to pregnancy rates and number of teratogenic events/100 live births in efavirenz-exposed women. Use of non-efavirenz-based initial ART in HIV-infected women of childbearing age may reduce life expectancy gains from antiretroviral treatment, but may also prevent teratogenic events. Decision-making regarding efavirenz use presents a trade-off between these two risks; this study can inform discussions between patients and health care providers.

32 CFR 183.6 - Procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Department of Defense OFFICE OF THE SECRETARY OF DEFENSE CIVIL DEFENSE DEFENSE SUPPORT OF SPECIAL EVENTS... initiated by the Department of Defense, civil authorities, or qualifying entities. If the initial engagement...) There are other events that the Department of Defense supports that do not involve the assignment of...

32 CFR 183.6 - Procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Department of Defense OFFICE OF THE SECRETARY OF DEFENSE CIVIL DEFENSE DEFENSE SUPPORT OF SPECIAL EVENTS... initiated by the Department of Defense, civil authorities, or qualifying entities. If the initial engagement...) There are other events that the Department of Defense supports that do not involve the assignment of...

32 CFR 183.6 - Procedures.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Department of Defense OFFICE OF THE SECRETARY OF DEFENSE CIVIL DEFENSE DEFENSE SUPPORT OF SPECIAL EVENTS... initiated by the Department of Defense, civil authorities, or qualifying entities. If the initial engagement...) There are other events that the Department of Defense supports that do not involve the assignment of...

Modeling the roles of damage accumulation and mechanical healing on rainfall-induced landslides

NASA Astrophysics Data System (ADS)

Fan, Linfeng; Lehmann, Peter; Or, Dani

2014-05-01

The abrupt release of rainfall-induced shallow landslides is preceded by local failures that may abruptly coalesce and form a continuous failure plane within a hillslope. The mechanical status of hillslopes reflects a competition between the extent of severity of accumulated local damage during prior rainfall events and the rates of mechanically healing (i.e. regaining of strength) by closure of micro-cracks, regrowth of roots, etc. The interplay of these processes affects the initial conditions for landslide modeling and shapes potential failure patterns during future rainfall events. We incorporated these competing mechanical processes in a hydro-mechanical landslide triggering model subjected to a sequence of rainfall scenarios. The model employs the Fiber Bundle Model (FBM) with bonds (fiber bundle) with prescribed threshold linking adjacent soil columns and soil to bedrock. Prior damage was represented by a fraction of broken fibers during previous rainfall events, and the healing of broken fibers was described by strength regaining models for soil and roots at different characteristic time scales. Results show that prior damage and healing introduce highly nonlinear response to landslide triggering. For small prior damage, mechanical bonds at soil-bedrock interface may fail early in next rainfall event but lead to small perturbations onto lateral bonds without triggering a landslide. For more severe damage weakening lateral bonds, excess load due to failure at soil-bedrock interface accumulates at downslope soil columns resulting in early soil failure with patterns strongly correlated with prior damage distribution. Increasing prior damage over the hillslope decreases the volume of first landslide and prolongs the time needed to trigger the second landslide due to mechanical relaxation of the system. The mechanical healing of fibers diminishes effects of prior damage on the time of failure, and shortens waiting time between the first and second landslides. These findings highlight the need to improve definition of initial conditions and the shortcomings of assuming pristine hillslopes.

A novel protein kinase D inhibitor attenuates early events of experimental pancreatitis in isolated rat acini.

PubMed

Thrower, Edwin C; Yuan, Jingzhen; Usmani, Ashar; Liu, Yannan; Jones, Courtney; Minervini, Samantha N; Alexandre, Martine; Pandol, Stephen J; Guha, Sushovan

2011-01-01

Novel protein kinase C isoforms (PKC δ and ε) mediate early events in acute pancreatitis. Protein kinase D (PKD/PKD1) is a convergent point of PKC δ and ε in the signaling pathways triggered through CCK or cholinergic receptors and has been shown to activate the transcription factor NF-κB in acute pancreatitis. For the present study we hypothesized that a newly developed PKD/PKD1 inhibitor, CRT0066101, would prevent the initial events leading to pancreatitis. We pretreated isolated rat pancreatic acinar cells with CRT0066101 and a commercially available inhibitor Gö6976 (10 μM). This was followed by stimulation for 60 min with high concentrations of cholecystokinin (CCK, 0.1 μM), carbachol (CCh, 1 mM), or bombesin (10 μM) to induce initial events of pancreatitis. PKD/PKD1 phosphorylation and activity were measured as well as zymogen activation, amylase secretion, cell injury and NF-κB activation. CRT0066101 dose dependently inhibited secretagogue-induced PKD/PKD1 activation and autophosphorylation at Ser-916 with an IC(50) ∼3.75-5 μM but had no effect on PKC-dependent phosphorylation of the PKD/PKD1 activation loop (Ser-744/748). Furthermore, CRT0066101 reduced secretagogue-induced zymogen activation and amylase secretion. Gö6976 reduced zymogen activation but not amylase secretion. Neither inhibitor affected basal zymogen activation or secretion. CRT0066101 did not affect secretagogue-induced cell injury or changes in cell morphology, but it reduced NF-κB activation by 75% of maximal for CCK- and CCh-stimulated acinar cells. In conclusion, CRT0066101 is a potent and specific PKD family inhibitor. Furthermore, PKD/PKD1 is a potential mediator of zymogen activation, amylase secretion, and NF-κB activation induced by a range of secretagogues in pancreatic acinar cells.

The pattern of childhood accidents in south-western Nigeria

PubMed Central

Sinnette, Calvin H.

1969-01-01

All childhood accidents treated at the University College Hospital, Ibadan, Nigeria, during a 4-year period are analysed. The pattern of childhood injuries in the part of Nigeria served by this hospital does not differ significantly from the pattern reported in studies from other parts of the world. The chain of events leading to an accident appears in large measure to be directly influenced by the mode of life in the community. This in turn is related to the prevailing level of technological development. There is an obvious need for more exhaustive studies of childhood accidents in developing countries. However, these countries need not wait for this information to become available before initiating accident-prevention programmes. PMID:5309535

Initiation of non-tropical thunderstorms by solar activity

NASA Technical Reports Server (NTRS)

Herman, J. R.; Goldberg, R. A.

1976-01-01

Correlative evidence accumulating since 1926 suggests that there must be some physical coupling mechanism between solar activity and thunderstorm occurrence in middle to high latitudes. Such a link may be provided by alteration of atmospheric electric parameters through the combined influence of high-energy solar protons and decreased cosmic ray intensities, both of which are associated with active solar events. The protons produce excess ionization near and above 20km, while the Forbush decreases a lowered conductivity and enhanced fair-weather atmospheric electric field below that altitude. Consequent effects ultimately lead to a charge distribution similar to that found in thunderclouds, and then other cloud physics processes take over to generate the intense electric fields required for lightning discharge.

Endocrine complications of topical and intralesional corticosteroid therapy.

PubMed

Curtis, J A; Cormode, E; Laski, B; Toole, J; Howard, N

1982-03-01

Four previously healthy children acquired skin problems that were treated with topical or intralesional fluorinated corticosteroids. Three developed signs that suggested Cushing's syndrome 1-4 months after initial treatment. Investigation showed low plasma cortisol levels and inadequate response to corticotrophin stimulation. After 7 months of treatment with topical steroids the fourth child presented with failure to thrive; during a febrile illness he had a convulsion followed by acute hypotension which responded to parenteral corticosteroid administration. Adrenal function was not studied in this patient. Although fluorinated corticosteroids seldom lead to overt adrenal suppression in children, they may impair pituitary-adrenal responses in some. Such patients should be given oral or parenteral steroid cover in the event of illness or trauma.

The Role of TLR2 in Infection and Immunity

PubMed Central

Oliveira-Nascimento, Laura; Massari, Paola; Wetzler, Lee M.

2012-01-01

Toll-like receptors (TLRs) are recognition molecules for multiple pathogens, including bacteria, viruses, fungi, and parasites. TLR2 forms heterodimers with TLR1 and TLR6, which is the initial step in a cascade of events leading to significant innate immune responses, development of adaptive immunity to pathogens and protection from immune sequelae related to infection with these pathogens. This review will discuss the current status of TLR2 mediated immune responses by recognition of pathogen-associated molecular patterns (PAMPS) on these organisms. We will emphasize both canonical and non-canonical responses to TLR2 ligands with emphasis on whether the inflammation induced by these responses contributes to the disease state or to protection from diseases. PMID:22566960

Fission product transport analysis in a loss of decay heat removal accident at Browns Ferry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wichner, R.P.; Weber, C.F.; Hodge, S.A.

1984-01-01

This paper summarizes an analysis of the movement of noble gases, iodine, and cesium fission products within the Mark-I containment BWR reactor system represented by Browns Ferry Unit 1 during a postulated accident sequence initiated by a loss of decay heat removal (DHR) capability following a scram. The event analysis showed that this accident could be brought under control by various means, but the sequence with no operator action ultimately leads to containment (drywell) failure followed by loss of water from the reactor vessel, core degradation due to overheating, and reactor vessel failure with attendant movement of core debris ontomore » the drywell floor.« less

Consensus recommendations on training and competing in the heat.

PubMed

Racinais, S; Alonso, J M; Coutts, A J; Flouris, A D; Girard, O; González-Alonso, J; Hausswirth, C; Jay, O; Lee, J K W; Mitchell, N; Nassis, G P; Nybo, L; Pluim, B M; Roelands, B; Sawka, M N; Wingo, J; Périard, J D

2015-09-01

Exercising in the heat induces thermoregulatory and other physiological strain that can lead to impairments in endurance exercise capacity. The purpose of this consensus statement is to provide up-to-date recommendations to optimise performance during sporting activities undertaken in hot ambient conditions. The most important intervention one can adopt to reduce physiological strain and optimise performance is to heat acclimatise. Heat acclimatisation should comprise repeated exercise-heat exposures over 1-2 weeks. In addition, athletes should initiate competition and training in a euhydrated state and minimise dehydration during exercise. Following the development of commercial cooling systems (eg, cooling-vest), athletes can implement cooling strategies to facilitate heat loss or increase heat storage capacity before training or competing in the heat. Moreover, event organisers should plan for large shaded areas, along with cooling and rehydration facilities, and schedule events in accordance with minimising the health risks of athletes, especially in mass participation events and during the first hot days of the year. Following the recent examples of the 2008 Olympics and the 2014 FIFA World Cup, sport governing bodies should consider allowing additional (or longer) recovery periods between and during events, for hydration and body cooling opportunities, when competitions are held in the heat. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Satellite-Enhanced Dynamical Downscaling of Extreme Events

NASA Astrophysics Data System (ADS)

Nunes, A.

2015-12-01

Severe weather events can be the triggers of environmental disasters in regions particularly susceptible to changes in hydrometeorological conditions. In that regard, the reconstruction of past extreme weather events can help in the assessment of vulnerability and risk mitigation actions. Using novel modeling approaches, dynamical downscaling of long-term integrations from global circulation models can be useful for risk analysis, providing more accurate climate information at regional scales. Originally developed at the National Centers for Environmental Prediction (NCEP), the Regional Spectral Model (RSM) is being used in the dynamical downscaling of global reanalysis, within the South American Hydroclimate Reconstruction Project. Here, RSM combines scale-selective bias correction with assimilation of satellite-based precipitation estimates to downscale extreme weather occurrences. Scale-selective bias correction is a method employed in the downscaling, similar to the spectral nudging technique, in which the downscaled solution develops in agreement with its coarse boundaries. Precipitation assimilation acts on modeled deep-convection, drives the land-surface variables, and therefore the hydrological cycle. During the downscaling of extreme events that took place in Brazil in recent years, RSM continuously assimilated NCEP Climate Prediction Center morphing technique precipitation rates. As a result, RSM performed better than its global (reanalysis) forcing, showing more consistent hydrometeorological fields compared with more sophisticated global reanalyses. Ultimately, RSM analyses might provide better-quality initial conditions for high-resolution numerical predictions in metropolitan areas, leading to more reliable short-term forecasting of severe local storms.

Biodegradability of organic matter associated with sewer sediments during first flush.

PubMed

Sakrabani, Ruben; Vollertsen, Jes; Ashley, Richard M; Hvitved-Jacobsen, Thorkild

2009-04-01

The high pollution load in wastewater at the beginning of a rain event is commonly known to originate from the erosion of sewer sediments due to the increased flow rate under storm weather conditions. It is essential to characterize the biodegradability of organic matter during a storm event in order to quantify the effect it can have further downstream to the receiving water via discharges from Combined Sewer Overflow (CSO). The approach is to characterize the pollutograph during first flush. The pollutograph shows the variation in COD and TSS during a first flush event. These parameters measure the quantity of organic matter present. However these parameters do not indicate detailed information on the biodegradability of the organic matter. Such detailed knowledge can be obtained by dividing the total COD into fractions with different microbial properties. To do so oxygen uptake rate (OUR) measurements on batches of wastewater have shown itself to be a versatile technique. Together with a conceptual understanding of the microbial transformation taking place, OUR measurements lead to the desired fractionation of the COD. OUR results indicated that the highest biodegradability is associated with the initial part of a storm event. The information on physical and biological processes in the sewer can be used to better manage sediment in sewers which can otherwise result in depletion of dissolved oxygen in receiving waters via discharges from CSOs.

Initiation of sleep-dependent cortical-hippocampal correlations at wakefulness-sleep transition.

PubMed

Haggerty, Daniel C; Ji, Daoyun

2014-10-01

Sleep is involved in memory consolidation. Current theories propose that sleep-dependent memory consolidation requires active communication between the hippocampus and neocortex. Indeed, it is known that neuronal activities in the hippocampus and various neocortical areas are correlated during slow-wave sleep. However, transitioning from wakefulness to slow-wave sleep is a gradual process. How the hippocampal-cortical correlation is established during the wakefulness-sleep transition is unknown. By examining local field potentials and multiunit activities in the rat hippocampus and visual cortex, we show that the wakefulness-sleep transition is characterized by sharp-wave ripple events in the hippocampus and high-voltage spike-wave events in the cortex, both of which are accompanied by highly synchronized multiunit activities in the corresponding area. Hippocampal ripple events occur earlier than the cortical high-voltage spike-wave events, and hippocampal ripple incidence is attenuated by the onset of cortical high-voltage spike waves. This attenuation leads to a temporary weak correlation in the hippocampal-cortical multiunit activities, which eventually evolves to a strong correlation as the brain enters slow-wave sleep. The results suggest that the hippocampal-cortical correlation is established through a concerted, two-step state change that first synchronizes the neuronal firing within each brain area and then couples the synchronized activities between the two regions. Copyright © 2014 the American Physiological Society.

Straits to Extinction. Integrated Magneto-Bio-Stratigraphy and Cyclostratigraphy Studies Reveal the Destructive Power of Marine Gateways

NASA Astrophysics Data System (ADS)

Palcu, D.; Simon, D.; da Silva, A. C.; Popov, S. V.; Golovina, L.; Krijgsman, W.

2016-12-01

The marine gateways are an important element in the geographic and paleogeographic architecture of oceans and seas. They influence the heat and chemical exchange between neighbouring water bodies, mixing or segregating them and influencing the climate and the ecosystems. In extreme configurations, they play a role in the onset of Salinity Crises and the formation of evaporites. However, detailed information on the sensitivity and functioning of gateways remains scarce as their geological records are poorly preserved. To counter the lack of reliable records our research focuses on the impact of the gateways on the adjacent seas. We studied marine sediments from basins that belonged to the Neogene system of seas and lakes of Eurasia (Paratethys). Integrated magneto-bio-stratigraphy and cyclostratigraphy studies in these basins have provided high-resolution correlations between the neighbouring seas within Paratethys, which, in turn, led to the identification of problematic gateway configurations. Here we focus on two such configurations: the setting that allows evaporite formation and the configuration that leads to extinction events. The gateway setting responsible for salinity crises not only leads to extinctions but also to the formation evaporites. We focus on the Badenian Salinity Crisis (BSC), an event that occurred between 13.8-13.3Ma, which is particularly interesting because it is a selective salinity crisis, happening only in some of the sub-basins of Paratethys. In this case, our initial evidence shows that the configuration requires multiple gateways that can produce water stratification and brine formation. The gateway configuration that triggers extinctions has been linked with the Badenian-Sarmatian Extinction Event (BSEE), placed at 12.65Ma. The event. that has completely destroyed the marine ecosystems of Central and Eastern Europe (with an extinction rate of 94%), has occurred in less than 10kyr and according to our numerical modelling results it only required a sea-level variation of 5m.

Mechanical strain induces involution-associated events in mammary epithelial cells

PubMed Central

Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C

2009-01-01

Background Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device specifically designed for such a purpose. We believe that our results indicate the relevance of mechanical stress among the early post-lactation events that lead to mammary gland involution. PMID:19615079

Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data.

PubMed

Cools, Filip; Askie, Lisa M; Offringa, Martin; Asselin, Jeanette M; Calvert, Sandra A; Courtney, Sherry E; Dani, Carlo; Durand, David J; Gerstmann, Dale R; Henderson-Smart, David J; Marlow, Neil; Peacock, Janet L; Pillow, J Jane; Soll, Roger F; Thome, Ulrich H; Truffert, Patrick; Schreiber, Michael D; Van Reempts, Patrick; Vendettuoli, Valentina; Vento, Giovanni

2010-06-12

Population and study design heterogeneity has confounded previous meta-analyses, leading to uncertainty about effectiveness and safety of elective high-frequency oscillatory ventilation (HFOV) in preterm infants. We assessed effectiveness of elective HFOV versus conventional ventilation in this group. We did a systematic review and meta-analysis of individual patients' data from 3229 participants in ten randomised controlled trials, with the primary outcomes of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age, death or severe adverse neurological event, or any of these outcomes. For infants ventilated with HFOV, the relative risk of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age was 0.95 (95% CI 0.88-1.03), of death or severe adverse neurological event 1.00 (0.88-1.13), or any of these outcomes 0.98 (0.91-1.05). No subgroup of infants (eg, gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids) benefited more or less from HFOV. Ventilator type or ventilation strategy did not change the overall treatment effect. HFOV seems equally effective to conventional ventilation in preterm infants. Our results do not support selection of preterm infants for HFOV on the basis of gestational age, birthweight for gestation, initial lung disease severity, or exposure to antenatal corticosteroids. Nestlé Belgium, Belgian Red Cross, and Dräger International.

Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling.

PubMed

Song, Min Jae; Bharti, Kapil

2016-05-01

Retinal degenerative diseases are the leading cause of irreversible vision loss in developed countries. In many cases the diseases originate in the homeostatic unit in the back of the eye that contains the retina, retinal pigment epithelium (RPE) and the choriocapillaris. RPE is a central and a critical component of this homeostatic unit, maintaining photoreceptor function and survival on the apical side and choriocapillaris health on the basal side. In diseases like age-related macular degeneration (AMD), it is thought that RPE dysfunctions cause disease-initiating events and as the RPE degenerates photoreceptors begin to die and patients start loosing vision. Patient-specific induced pluripotent stem (iPS) cell-derived RPE provides direct access to a patient's genetics and allow the possibility of identifying the initiating events of RPE-associated degenerative diseases. Furthermore, iPS cell-derived RPE cells are being tested as a potential cell replacement in disease stages with RPE atrophy. In this article we summarize the recent progress in the field of iPS cell-derived RPE "disease modeling" and cell therapies and also discuss the possibilities of developing a model of the entire homeostatic unit to aid in studying disease processes in the future. This article is part of a Special Issue entitled SI: PSC and the brain. Published by Elsevier B.V.

Isocitrate dehydrogenase mutation as a therapeutic target in gliomas.

PubMed

Han, Catherine H; Batchelor, Tracy T

2017-06-01

Isocitrate dehydrogenases (IDH) are important enzymes that catalyze the oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG), producing NADPH in the process. More than 80% of low-grade gliomas and secondary glioblastoma (GBM) harbor an IDH mutation. IDH mutations involve the catalytic pocket of the enzyme and lead to a neomorphic ability to produce 2-hydroxyglutarate (2HG) while oxidizing NADPH to NADP+. 2HG is considered as an 'oncometabolite' which is thought to be responsible for many, if not all, biologic effects of IDH mutations. 2HG accumulation competitively inhibits α-KG-dependent dioxygenases, including histone lysine demethylases and DNA demethylases, resulting in a hypermethylation phenotype with alterations in cellular epigenetic status as well as a block in cellular differentiation. IDH mutations have been suggested as an important early event in tumorigenesis, however it remains unclear whether IDH mutation by itself causes cancer or if it requires other oncogenic events to initiate tumorigenesis. Significant efforts have been made to better understand the mechanisms of IDH mutations in tumor initiation and progression, and to develop targeted therapies for IDH-mutated tumors. This review provides an overview of the function of mutant IDH, and the current understanding of the role IDH mutations play in gliomagenesis. In addition, several potential therapeutic strategies for IDH-mutant gliomas, including mutant IDH inhibitors which have entered clinical evaluation in glioma patients, will be discussed.

RAGE mediates the inactivation of nAChRs in sympathetic neurons under high glucose conditions.

PubMed

Chandna, Andrew R; Nair, Manoj; Chang, Christine; Pennington, Paul R; Yamamoto, Yasuhiko; Mousseau, Darrell D; Campanucci, Verónica A

2015-02-01

Autonomic dysfunction is a serious complication of diabetes and can lead to cardiovascular abnormalities and premature death. It was recently proposed that autonomic dysfunction is triggered by oxidation-mediated inactivation of neuronal nicotinic acetylcholine receptors (nAChRs), impairing synaptic transmission in sympathetic ganglia and resulting in autonomic failure. We investigated whether the receptor for advanced glycation end products (RAGE) and its role in the generation of reactive oxygen species (ROS) could be contributing to the events that initiate sympathetic malfunction under high glucose conditions. Using biochemical, live imaging and electrophysiological tools we demonstrated that exposure of sympathetic neurons to high glucose increases RAGE expression and oxidative markers, and that incubation with RAGE ligands (e.g. AGEs, S100 and HMGB1) mimics both ROS elevation and nAChR inactivation. In contrast, co-treatment with either antioxidants or an anti-RAGE IgG prevented the inactivation of nAChRs. Lastly, a role for RAGE in this context was corroborated by the lack of sensitivity of sympathetic neurons from RAGE knock-out mice to high glucose. These data define a pivotal role for RAGE in initiating the events associated with exposure of sympathetic neurons to high glucose, and strongly support RAGE signaling as a potential therapeutic target in the autonomic complications associated with diabetes. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Does pressure cause liver cirrhosis? The sinusoidal pressure hypothesis.

PubMed

Mueller, Sebastian

2016-12-28

Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a major health problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis (SPH), which identifies an elevated sinusoidal pressure (SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts (SPH part I: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmHg and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures (SPH part II: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.

Future climate risk from compound events

NASA Astrophysics Data System (ADS)

Zscheischler, Jakob; Westra, Seth; van den Hurk, Bart J. J. M.; Seneviratne, Sonia I.; Ward, Philip J.; Pitman, Andy; AghaKouchak, Amir; Bresch, David N.; Leonard, Michael; Wahl, Thomas; Zhang, Xuebin

2018-06-01

Floods, wildfires, heatwaves and droughts often result from a combination of interacting physical processes across multiple spatial and temporal scales. The combination of processes (climate drivers and hazards) leading to a significant impact is referred to as a `compound event'. Traditional risk assessment methods typically only consider one driver and/or hazard at a time, potentially leading to underestimation of risk, as the processes that cause extreme events often interact and are spatially and/or temporally dependent. Here we show how a better understanding of compound events may improve projections of potential high-impact events, and can provide a bridge between climate scientists, engineers, social scientists, impact modellers and decision-makers, who need to work closely together to understand these complex events.

ARM Support for the Plains Elevated Convection at Night (AS-PECAN) Field Campaign Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turner, D. D.; Geerts, B.

The Plains Elevated Convection at Night (PECAN) field campaign was a large multi-agency/multi-institutional experiment that targeted nighttime convection events in the central plains of the United States in order to better understand a range of processes that lead to the initiation and upscale growth of deep convection. Both weather and climate models struggle to properly represent the timing and intensity of precipitation in the central United States in their simulations. These models must be able to represent the interactions between the nocturnal stable boundary layer (SBL), the nocturnal low-level jet (LLJ), and a reservoir of convectively available potential energy (CAPE)more » that frequently exists above the SBL. Furthermore, a large fraction of the nocturnal precipitation is due to the organization of mesoscale convective systems (MCSs). In particular, there were four research foci for the PECAN campaign: •The initiation of elevated nocturnal convection focus seeks to elucidate the mesoscaleenvironmental characteristics and processes that lead to convection initiation (CI) and provide baseline data on the early evolution of mesoscale convective clusters. •The dynamics and internal structure and microphysics of nocturnal MCSs focus will investigatethe transition from surface-based to elevated storm structure, the interaction of cold pools generated by MCSs with the nocturnal stable boundary layer, and how the organization and evolution of elevated convection is influenced by the SBL and the vertical profile of wind and stability above the LLJ. •The bores and wave-like disturbances focus seeks to advance knowledge of the initiation of boredisturbances by convection, how the vertical profile of stability and winds modulate bore structure, the role of these disturbances in the initiation, maintenance, and organization of deep convection, and their impact on the LLJ and SBL. •The LLJ focus seeks to understand the processes that influence the spatial and temporal evolutionof the LLJ, how it affects the SBL, and the interaction between the LLJ and atmospheric boundaries in the development of CI.« less

Lightning Initiation Forecasting: An Operational Dual-Polarimetric Radar Technique

NASA Technical Reports Server (NTRS)

Woodard, Crystal J.; Carey, L. D.; Petersen, W. A.; Roeder, W. P.

2011-01-01

The objective of this NASA MSFC and NOAA CSTAR funded study is to develop and test operational forecast algorithms for the prediction of lightning initiation utilizing the C-band dual-polarimetric radar, UAHuntsville's Advanced Radar for Meteorological and Operational Research (ARMOR). Although there is a rich research history of radar signatures associated with lightning initiation, few studies have utilized dual-polarimetric radar signatures (e.g., Z(sub dr) columns) and capabilities (e.g., fuzzy-logic particle identification [PID] of precipitation ice) in an operational algorithm for first flash forecasting. The specific goal of this study is to develop and test polarimetric techniques that enhance the performance of current operational radar reflectivity based first flash algorithms. Improving lightning watch and warning performance will positively impact personnel safety in both work and leisure environments. Advanced warnings can provide space shuttle launch managers time to respond appropriately to secure equipment and personnel, while they can also provide appropriate warnings for spectators and players of leisure sporting events to seek safe shelter. Through the analysis of eight case dates, consisting of 35 pulse-type thunderstorms and 20 non-thunderstorm case studies, lightning initiation forecast techniques were developed and tested. The hypothesis is that the additional dual-polarimetric information could potentially reduce false alarms while maintaining high probability of detection and increasing lead-time for the prediction of the first lightning flash relative to reflectivity-only based techniques. To test the hypothesis, various physically-based techniques using polarimetric variables and/or PID categories, which are strongly correlated to initial storm electrification (e.g., large precipitation ice production via drop freezing), were benchmarked against the operational reflectivity-only based approaches to find the best compromise between forecast skill and lead-time. Forecast skill is determined by statistical analysis of probability of detection (POD), false alarm ratio (FAR), Operational Utility Index (OUI), and critical success index (CSI).

The occurrence of individual slow waves in sleep is predicted by heart rate

PubMed Central

Mensen, Armand; Zhang, Zhongxing; Qi, Ming; Khatami, Ramin

2016-01-01

The integration of near-infrared spectroscopy and electroencephalography measures presents an ideal method to study the haemodynamics of sleep. While the cortical dynamics and neuro-modulating influences affecting the transition from wakefulness to sleep is well researched, the assumption has been that individual slow waves, the hallmark of deep sleep, are spontaneously occurring cortical events. By creating event-related potentials from the NIRS recording, time-locked to the onset of thousands of individual slow waves, we show the onset of slow waves is phase-locked to an ongoing oscillation in the NIRS recording. This oscillation stems from the moment to moment fluctuations of light absorption caused by arterial pulsations driven by the heart beat. The same oscillating signal can be detected if the electrocardiogram is time-locked to the onset of the slow wave. The ongoing NIRS oscillation suggests that individual slow wave initiation is dependent on that signal, and not the other way round. However, the precise causal links remain speculative. We propose several potential mechanisms: that the heart-beat or arterial pulsation acts as a stimulus which evokes a down-state; local fluctuations in energy supply may lead to a network effect of hyperpolarization; that the arterial pulsations lead to corresponding changes in the cerebral-spinal-fluid which evokes the slow wave; or that a third neural generator, regulating heart rate and slow waves may be involved. PMID:27445083

Unraveling the early molecular and physiological mechanisms involved in response to phenanthrene exposure.

PubMed

Dumas, Anne-Sophie; Taconnat, Ludivine; Barbas, Evangelos; Rigaill, Guillem; Catrice, Olivier; Bernard, Delphine; Benamar, Abdelilah; Macherel, David; El Amrani, Abdelhak; Berthomé, Richard

2016-10-21

Higher plants have to cope with increasing concentrations of pollutants of both natural and anthropogenic origin. Given their capacity to concentrate and metabolize various compounds including pollutants, plants can be used to treat environmental problems - a process called phytoremediation. However, the molecular mechanisms underlying the stabilization, the extraction, the accumulation and partial or complete degradation of pollutants by plants remain poorly understood. Here, we determined the molecular events involved in the early plant response to phenanthrene, used as a model of polycyclic aromatic hydrocarbons. A transcriptomic and a metabolic analysis strongly suggest that energy availability is the crucial limiting factor leading to high and rapid transcriptional reprogramming that can ultimately lead to death. We show that the accumulation of phenanthrene in leaves inhibits electron transfer and photosynthesis within a few minutes, probably disrupting energy transformation. This kinetic analysis improved the resolution of the transcriptome in the initial plant response to phenanthrene, identifying genes that are involved in primary processes set up to sense and detoxify this pollutant but also in molecular mechanisms used by the plant to cope with such harmful stress. The identification of first events involved in plant response to phenanthrene is a key step in the selection of candidates for further functional characterization, with the prospect of engineering efficient ecological detoxification systems for polycyclic aromatic hydrocarbons.

Use of dietary phytochemicals to target inflammation, fibrosis, proliferation, and angiogenesis in uterine tissues: promising options for prevention and treatment of uterine fibroids?

PubMed

Islam, Md Soriful; Akhtar, Most Mauluda; Ciavattini, Andrea; Giannubilo, Stefano Raffaele; Protic, Olga; Janjusevic, Milijana; Procopio, Antonio Domenico; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina

2014-08-01

Uterine leiomyomas (fibroids, myomas) are the most common benign tumors of female reproductive tract. They are highly prevalent, with 70-80% of women burdened by the end of their reproductive years. Fibroids are a leading cause of pelvic pain, abnormal vaginal bleeding, pressure on the bladder, miscarriage, and infertility. They are the leading indication for hysterectomy, and costs exceed 6 billion dollars annually in the United States. Unfortunately, no long-term medical treatments are available. Dysregulation of inflammatory processes are thought to be involved in the initiation of leiomyoma and extracellular matrix deposition, cell proliferation, and angiogenesis are the key cellular events implicated in leiomyoma growth. In modern pharmaceutical industries, dietary phytochemicals are used as source of new potential drugs for many kinds of tumors. Dietary phytochemicals may exert therapeutic effects by interfering with key cellular events of the tumorigenesis process. At present, a negligible number of phytochemicals have been tested as therapeutic agents against fibroids. In this context, our aim was to introduce some of the potential dietary phytochemicals that have shown anti-inflammatory, antiproliferative, antifibrotic, and antiangiogenic activities in different biological systems. This review could be useful to stimulate the evaluation of these phytochemicals as possible therapies for uterine fibroids. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of a tiered screening strategy for a molecular-initiating event: thyroperoxidase inhibition (SOT)

EPA Science Inventory

Adverse outcome pathway (AOP) analyses illustrate that some molecular-initiating events (MIEs) for thyroid disruption, including thyroperoxidase (TPO) inhibition, are not evaluated by current ToxCast/Tox21 high-throughput screening (HTS) assays. A novel HTS assay for TPO inhibiti...

A novel approach to increase residents' involvement in reporting adverse events.

PubMed

Scott, David R; Weimer, Melissa; English, Clea; Shaker, Lynn; Ward, William; Choi, Dongseok; Cedfeldt, Andrea; Girard, Donald

2011-06-01

In the wake of the Patient Safety and Quality Improvement Act of 2005, national attention has increasingly focused on adverse-event reporting as a means of identifying systems changes to improve patient safety. However, physicians and residents have demonstrated meager involvement in this effort. In 2008-2009, the authors measured participation in adverse-event reporting by 680 residents at Oregon Health & Science University before and after implementing a quality improvement initiative, which consisted of a financial incentive and multifaceted educational campaign. The primary measure of success was an increase in the average monthly adverse-event reports submitted by residents to greater than 5% of the institution's overall report submissions. The average number of adverse events reported by residents increased from 1.6% to 9.0% of the institution's overall event reports, representing a 5.6-fold increase during the initiative (P < .001). The relative percentage of resident-submitted reports defined as "near-misses" increased from 6% to 27% during the initiative (P < .001). The novel approach of integrating a retirement benefit and educational campaign to increase residents' involvement in adverse-event reporting was successful. In addition to increasing residents' contributions to adverse-event reporting to levels higher than any documented in the current literature, there was also a remarkable increase in the relative frequency of near-miss reporting by residents.

A laboratory nanoseismological study on deep-focus earthquake micromechanics

DOE PAGES

Wang, Yanbin; Zhu, Lupei; Shi, Feng; ...

2017-07-21

Global earthquake occurring rate displays an exponential decay down to ~300 km and then peaks around 550 to 600 km before terminating abruptly near 700 km. How fractures initiate, nucleate, and propagate at these depths remains one of the greatest puzzles in earth science, as increasing pressure inhibits fracture propagation. We report nanoseismological analysis on high-resolution acoustic emission (AE) records obtained during ruptures triggered by partial transformation from olivine to spinel in Mg 2GeO 4, an analog to the dominant mineral (Mg,Fe) 2SiO 4 olivine in the upper mantle, using state-of-the-art seismological techniques, in the laboratory. AEs’ focal mechanisms, asmore » well as their distribution in both space and time during deformation, are carefully analyzed. Microstructure analysis shows that AEs are produced by the dynamic propagation of shear bands consisting of nanograined spinel. These nanoshear bands have a near constant thickness (~100 nm) but varying lengths and self-organize during deformation. This precursory seismic process leads to ultimate macroscopic failure of the samples. Several source parameters of AE events were extracted from the recorded waveforms, allowing close tracking of event initiation, clustering, and propagation throughout the deformation/transformation process. AEs follow the Gutenberg-Richter statistics with a well-defined b value of 1.5 over three orders of moment magnitudes, suggesting that laboratory failure processes are self-affine. The seismic relation between magnitude and rupture area correctly predicts AE magnitude at millimeter scales. A rupture propagation model based on strain localization theory is proposed. Future numerical analyses may help resolve scaling issues between laboratory AE events and deep-focus earthquakes.« less

A laboratory nanoseismological study on deep-focus earthquake micromechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanbin; Zhu, Lupei; Shi, Feng

Global earthquake occurring rate displays an exponential decay down to ~300 km and then peaks around 550 to 600 km before terminating abruptly near 700 km. How fractures initiate, nucleate, and propagate at these depths remains one of the greatest puzzles in earth science, as increasing pressure inhibits fracture propagation. We report nanoseismological analysis on high-resolution acoustic emission (AE) records obtained during ruptures triggered by partial transformation from olivine to spinel in Mg2GeO4, an analog to the dominant mineral (Mg,Fe)2SiO4 olivine in the upper mantle, using state-of-the-art seismological techniques, in the laboratory. AEs’ focal mechanisms, as well as their distributionmore » in both space and time during deformation, are carefully analyzed. Microstructure analysis shows that AEs are produced by the dynamic propagation of shear bands consisting of nanograined spinel. These nanoshear bands have a near constant thickness (~100 nm) but varying lengths and self-organize during deformation. This precursory seismic process leads to ultimate macroscopic failure of the samples. Several source parameters of AE events were extracted from the recorded waveforms, allowing close tracking of event initiation, clustering, and propagation throughout the deformation/transformation process. AEs follow the Gutenberg-Richter statistics with a well-defined b value of 1.5 over three orders of moment magnitudes, suggesting that laboratory failure processes are self-affine. The seismic relation between magnitude and rupture area correctly predicts AE magnitude at millimeter scales. A rupture propagation model based on strain localization theory is proposed. Future numerical analyses may help resolve scaling issues between laboratory AE events and deep-focus earthquakes.« less

A laboratory nanoseismological study on deep-focus earthquake micromechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yanbin; Zhu, Lupei; Shi, Feng

Global earthquake occurring rate displays an exponential decay down to ~300 km and then peaks around 550 to 600 km before terminating abruptly near 700 km. How fractures initiate, nucleate, and propagate at these depths remains one of the greatest puzzles in earth science, as increasing pressure inhibits fracture propagation. We report nanoseismological analysis on high-resolution acoustic emission (AE) records obtained during ruptures triggered by partial transformation from olivine to spinel in Mg 2GeO 4, an analog to the dominant mineral (Mg,Fe) 2SiO 4 olivine in the upper mantle, using state-of-the-art seismological techniques, in the laboratory. AEs’ focal mechanisms, asmore » well as their distribution in both space and time during deformation, are carefully analyzed. Microstructure analysis shows that AEs are produced by the dynamic propagation of shear bands consisting of nanograined spinel. These nanoshear bands have a near constant thickness (~100 nm) but varying lengths and self-organize during deformation. This precursory seismic process leads to ultimate macroscopic failure of the samples. Several source parameters of AE events were extracted from the recorded waveforms, allowing close tracking of event initiation, clustering, and propagation throughout the deformation/transformation process. AEs follow the Gutenberg-Richter statistics with a well-defined b value of 1.5 over three orders of moment magnitudes, suggesting that laboratory failure processes are self-affine. The seismic relation between magnitude and rupture area correctly predicts AE magnitude at millimeter scales. A rupture propagation model based on strain localization theory is proposed. Future numerical analyses may help resolve scaling issues between laboratory AE events and deep-focus earthquakes.« less

Wintertime component of the THORPEX Pacific-Asian Regional Campaign (T-PARC)

NASA Astrophysics Data System (ADS)

Song, Y.; Toth, Z.; Asuma, Y.; Reynolds, C.; Lngland, R.; Szunyogh, I.; Colle, B.; Chang, E.; Doyle, C.; Kats, A.

2009-04-01

The winter component of the T-PARC is an international field project that aims at improving high impact weather event forecasts for North America. The main objective is to understand how perturbations from the tropics, Eurasia and polar fronts travel through waveguide and turn into high impact weather events. Through adaptive observations by using manned aircrafts (NOAA G-IV and US Air force C-130s) and Russian rawinsonde network over data sparse regions, it is expected that accurate initial conditions will improve the numerical weather forecasts. Non-adaptive aircraft measurements over the Pacific Rim and part of India are also deployed through E-AMDAR program, which is expected to improve the background field over Asia where perturbations are initiated. The campaign is led by NOAA and joined by agencies and universities from US, Canada, Mexico, Japan, ECWMF, and Russia. While most observational data will be assimilated by operational centers to improve real time numerical weather predictions, post field studies will focus on aspects such as: data impact on forecast and analysis, dry and moist processes that affect the formation and propagation of perturbations, meso-scale storm structure, error growth, forecast "busts" under certain atmospheric regimes, and socio-economic applications such as costs and benefits of improved forecasts and their use by the public for high impact weather events. In particular, a Winter Olympics demonstration project (February 12 - February 28) is expected to be a test bed during winter T-PARC for real user outreach and application purposes. Effectiveness of existing targeting methods as well as new targeting methods in the 3-5 day lead time range will be pursued and other aspects related to data assimilation and numerical forecasts (both deterministic and ensemble forecasts) will be investigated within this project as well.

New formulations for tsunami runup estimation

NASA Astrophysics Data System (ADS)

Kanoglu, U.; Aydin, B.; Ceylan, N.

2017-12-01

We evaluate shoreline motion and maximum runup in two folds: One, we use linear shallow water-wave equations over a sloping beach and solve as initial-boundary value problem similar to the nonlinear solution of Aydın and Kanoglu (2017, Pure Appl. Geophys., https://doi.org/10.1007/s00024-017-1508-z). Methodology we present here is simple; it involves eigenfunction expansion and, hence, avoids integral transform techniques. We then use several different types of initial wave profiles with and without initial velocity, estimate shoreline properties and confirm classical runup invariance between linear and nonlinear theories. Two, we use the nonlinear shallow water-wave solution of Kanoglu (2004, J. Fluid Mech. 513, 363-372) to estimate maximum runup. Kanoglu (2004) presented a simple integral solution for the nonlinear shallow water-wave equations using the classical Carrier and Greenspan transformation, and further extended shoreline position and velocity to a simpler integral formulation. In addition, Tinti and Tonini (2005, J. Fluid Mech. 535, 33-64) defined initial condition in a very convenient form for near-shore events. We use Tinti and Tonini (2005) type initial condition in Kanoglu's (2004) shoreline integral solution, which leads further simplified estimates for shoreline position and velocity, i.e. algebraic relation. We then use this algebraic runup estimate to investigate effect of earthquake source parameters on maximum runup and present results similar to Sepulveda and Liu (2016, Coast. Eng. 112, 57-68).

Climate variability and the European agricultural production

NASA Astrophysics Data System (ADS)

Guimarães Nobre, Gabriela; Hunink, Johannes E.; Baruth, Bettina; Aerts, Jeroen C. J. H.; Ward, Philip J.

2017-04-01

By 2050, the global demand for maize, wheat and other major crops is expected to grow sharply. To meet this challenge, agricultural systems have to increase substantially their production. However, the expanding world population, coupled with a decline of arable land per person, and the variability in global climate, are obstacles to achieving the increasing demand. Creating a resilient agriculture system requires the incorporation of preparedness measures against weather-related events, which can trigger disruptive risks such as droughts. This study examines the influence of large-scale climate variability on agriculture production applying a robust decision-making tool named fast-and-frugal trees (FFT). We created FFTs using a dataset of crop production and indices of climate variability: the El Niño Southern Oscillation (SOI) and the North Atlantic Oscillation (NAO). Our main goal is to predict the occurrence of below-average crop production, using these two indices at different lead times. Initial results indicated that SOI and NAO have strong links with European low sugar beet production. For some areas, the FFTs were able to detect below-average productivity events six months before harvesting with hit rate and predictive positive value higher than 70%. We found that shorter lead times, such as three months before harvesting, have the highest predictive skill. Additionally, we observed that the responses of low production events to the phases of the NAO and SOI vary spatially and seasonally. Through the comprehension of the relationship between large scale climate variability and European drought related agricultural impact, this study reflects on how this information could potentially improve the management of the agricultural sector by coupling the findings with seasonal forecasting system of crop production.

Seismic Monitoring of Rock Falls in Yosemite National Park

NASA Astrophysics Data System (ADS)

Zimmer, V. L.; Stock, G. M.; Sitar, N.

2008-12-01

Between 1857 and 2007, more than 600 landslide events have been documented in Yosemite National Park, with the vast majority of events occurring as rock falls in Yosemite Valley. The conditions leading to and triggering rock fall are understood in approximately 50 percent of cases, but in the other 50 percent, there were no apparent triggers. Occasionally, large rock falls have been preceded by smaller events that, in retrospect, may have been precursors. Close range seismic monitoring presents an opportunity to study the conditions leading up to rock fall, as well as the mechanics of the actual rock fall as recorded seismically. During the winter of 2007-08, we conducted a rock fall seismic monitoring feasibility study in Yosemite Valley. A station consisting of an 8 Hz geophone and an accelerometer was placed on a ledge 1000 feet above the valley floor, in a historically active rock fall area known as the Three Brothers. At least two rock falls in this area were recorded by the instrumentation and witnessed by visitors, representing the first time rock falls have been recorded with seismic instrumentation in Yosemite Valley. Significant energy was recorded in a wide frequency range, from a few Hz to approximately 150 Hz, limited by the geophone response and attenuation of the signal due to distance to the source (400 m). Furthermore, there exists a weak signal approximately 5-10 seconds before the obvious rock fall signature. We hypothesize that the weak signal represents rock fall initiation manifesting as the first blocks sliding down the cliff face, while the stronger impulses represent these blocks impacting ledges and the bottom talus field. This study demonstrated that rock fall monitoring is feasible with seismic instrumentation, and serves as the catalyst for future studies using a network of sensors for more advanced analysis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guidarelli, Andrea; Fiorani, Mara; Carloni, Silvia

We herein report the results from a comparative study of arsenite toxicity in respiration-proficient (RP) and -deficient (RD) U937 cells. An initial characterization of these cells led to the demonstration that the respiration-deficient phenotype is not associated with apparent changes in mitochondrial mass and membrane potential. In addition, similar levels of superoxide (O{sub 2}{sup .-}) were generated by RP and RD cells in response to stimuli specifically triggering respiratory chain-independent mitochondrial mechanisms or extramitochondrial, NADPH-oxidase dependent, mechanisms. At the concentration of 2.5 μM, arsenite elicited selective formation of O{sub 2}{sup .-} in the respiratory chain of RP cells, with hardlymore » any contribution of the above mechanisms. Under these conditions, O{sub 2}{sup .-} triggered downstream events leading to endoplasmic reticulum (ER) stress, autophagy and apoptosis. RD cells challenged with similar levels of arsenite failed to generate O{sub 2}{sup .-} because of the lack of a functional respiratory chain and were therefore resistant to the toxic effects mediated by the metalloid. Their resistance, however, was lost after exposure to four fold greater concentrations of arsenite, coincidentally with the release of O{sub 2}{sup .-} mediated by NADPH oxidase. Interestingly, extramitochondrial O{sub 2}{sup .-} triggered the same downstream events and an identical mode of death previously observed in RP cells. Taken together, the results obtained in this study indicate that arsenite toxicity is strictly dependent on O{sub 2}{sup .-} availability that, regardless of whether generated in the mitochondrial or extramitochondrial compartments, triggers similar downstream events leading to ER stress, autophagy and apoptosis. - Highlights: • Mitochondrial superoxide mediates arsenite toxicity in respiration-proficient cells. • NADPH-derived superoxide mediates arsenite toxicity in respiration-deficient cells. • Arsenite causes apoptosis in respiration-proficient and -deficient cells. • Apoptosis is in both circumstances associated with ER stress and autophagy.« less

An Old Problem: Aging and Skeletal-Muscle-Strain Injury.

PubMed

Baker, Brent A

2017-04-01

Clinical Scenario: Even though chronological aging is an inevitable phenomenological consequence occurring in every living organism, it is biological aging that may be the most significant factor challenging our quality of life. Development of functional limitations, resulting from improper maintenance and restoration of various organ systems, ultimately leads to reduced health and independence. Skeletal muscle is an organ system that, when challenged, is often injured in response to varying stimuli. Overt muscle-strain injury can be traumatic, clinically diagnosable, properly managed, and a remarkably common event, yet our contemporary understanding of how age and environmental stressors affect the initial and subsequent induction of injury and how the biological processes resulting from this event are modifiable and, eventually, lead to functional restoration and healing of skeletal muscle and adjacent tissues is presently unclear. Even though the secondary injury response to and recovery from "contraction-induced" skeletal-muscle injury are impaired with aging, there is no scientific consensus as to the exact mechanism responsible for this event. Given the multitude of investigative approaches, particular consideration given to the appropriateness of the muscle-injury model, or research paradigm, is critical so that outcomes may be physiologically relevant and translational. In this case, methods implementing stretch-shortening contractions, the most common form of muscle movements used by all mammals during physical movement, work, and activity, are highlighted. Understanding the fundamental evidence regarding how aging influences the responsivity of skeletal muscle to strain injury is vital for informing how clinicians approach and implement preventive strategies, as well as therapeutic interventions. From a practical perspective, maintaining or improving the overall health and tissue quality of skeletal muscle as one ages will positively affect skeletal muscle's safety threshold and responsivity, which may reduce incidence of injury, improve recovery time, and lessen overall fiscal burdens.

Using Smart Planning to Mitigate Drought in Urban Areas: A Seasonal Simulation of the Impact of Urbanization on Precipitation in the Indianapolis Region

NASA Astrophysics Data System (ADS)

Schmid, P. E.; Niyogi, D.

2012-12-01

The Indianapolis region exhibits a precipitation distribution indicative of urban weather modification: negative bias upwind and positive bias downwind. The causes for such a distribution within an urban area arise from a combination of land-surface heterogeneity and urban aerosol-cloud interaction. This study investigates the causes of the precipitation distribution with a 120-day simulation using the Regional Atmospheric Modeling System (RAMS) coupled with the Town Energy Budget (TEB) model. Using a nested grid with a maximum resolution of 500m, a seasonal simulation of May through August, 2008 is conducted. Land surface conditions are varied, removing, expanding, and intensifying the Indianapolis urban area. Aerosol conditions are scaled by a three-dimensional combination of MODIS and CALIPSO observations, and varied in concentration and plume extent. Results from the study demonstrate the paradigm of urban precipitation modification on a seasonal time scale. The boundary between the rural and urban land surfaces weakens approaching systems upwind, decreasing precipitation in the city center. A larger urban extent diminishes the systems further. The aerosol plume downwind increases cloud lifetimes via cloud-nucleating aerosol, then invigorates precipitation via large drizzle-invigorating aerosols. The overall effect reproduces the observed negative precipitation bias upwind and positive bias downwind of the urban center. A lower concentration of aerosols leads to a higher proportion of stratiform rain over a larger area, whereas a higher concentration of aerosols leads to more convective rain and heavy rain events. This manifests in a weekly cycle of precipitation with rain most likely on weekends, and with less frequent but heavier rain events most likely during midweek, when aerosol concentrations are the highest. More intense urbanization, via both land surface and aerosol effects, creates more frequent heavy rainfall events and exacerbates dry-periods, potentially leading to premature drought onset. The wetter than average May, June, and July received more total rainfall from the heavy rainfall events, while the dry August became drier due to lack of stratiform precipitation. Smart planning solutions can partially mitigate the urban precipitation problem. In a simulation where a more intense urban Indianapolis is surrounded by a greenbelt and green roofs are implemented in the city, the urban precipitation bias becomes less significant. Upwind, the greenbelt provides surface moisture and mitigates how much precipitation systems weaken. Downwind, the greenbelt slows the transport of drizzle-invigorating aerosol, reducing the heavy rain events. The green roofs reduce the urban-rural gradient and slow the initial weakening of systems.

Meteorological factors and timing of the initiating event of human parturition

NASA Astrophysics Data System (ADS)

Hirsch, Emmet; Lim, Courtney; Dobrez, Deborah; Adams, Marci G.; Noble, William

2011-03-01

The aim of this study was to determine whether meteorological factors are associated with the timing of either onset of labor with intact membranes or rupture of membranes prior to labor—together referred to as `the initiating event' of parturition. All patients delivering at Evanston Hospital after spontaneous labor or rupture of membranes at ≥20 weeks of gestation over a 6-month period were studied. Logistic regression models of the initiating event of parturition using clinical variables (maternal age, gestational age, parity, multiple gestation and intrauterine infection) with and without the addition of meteorological variables (barometric pressure, temperature and humidity) were compared. A total of 1,088 patients met the inclusion criteria. Gestational age, multiple gestation and chorioamnionitis were associated with timing of initiation of parturition ( P < 0.01). The addition of meteorological to clinical variables generated a statistically significant improvement in prediction of the initiating event; however, the magnitude of this improvement was small (less than 2% difference in receiver-operating characteristic score). These observations held regardless of parity, fetal number and gestational age. Meteorological factors are associated with the timing of parturition, but the magnitude of this association is small.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

PubMed

van Gestel, Aukje; Webers, Carroll A; Severens, Johan L; Beckers, Henny J; Jansonius, Nomdo M; Hendrikse, Fred; Schouten, Jan S

2012-02-01

To evaluate the long-term effects and costs of four treatment strategies for primary open-angle glaucoma compared to usual care. Cost-effectiveness analyses with a lifelong horizon were made from a societal perspective. Data were generated with a patient-level model based on discrete event simulation. The model structure and parameter estimates were based on literature, particularly clinical studies on the natural course of glaucoma and the effect of treatment. We simulated heterogeneous cohorts of 3000 patients and explored the impact of uncertainty with sensitivity analyses. The incremental cost-effectiveness ratio (ICER) of initial treatment with a prostaglandin analogue compared with a β-blocker was €12.931 per quality-adjusted life year (QALY) gained. A low initial target pressure (15 mmHg) resulted in 0.115 QALYs gained and €1550 saved compared to a gradual decrease from 21 to 15 mmHg upon progression. Visual field (VF) measurements every 6 rather than 12 months lead to health gains at increased costs (ICER €173,486 per QALY gained), whereas measurements every 24 months lead to health losses at reduced costs (ICER €21,516 per QALY lost). All treatment strategies were dominant over 'withholding treatment'. From a cost-effectiveness point of view, it seems advantageous to aim for a low intraocular pressure in all glaucoma patients. The feasibility of this strategy should therefore be investigated. Additionally, the cost-effectiveness outcomes of initiating monotherapy with a prostaglandin analogue and reducing the frequency of VF testing may be acceptable. © 2012 The Authors. Acta Ophthalmologica © 2012 Acta Ophthalmologica Scandinavica Foundation.

 Early initiation of MARS® dialysis in Amanita phalloides-induced acute liver injury prevents liver transplantation.

PubMed

Pillukat, Mike Hendrik; Schomacher, Tina; Baier, Peter; Gabriëls, Gert; Pavenstädt, Hermann; Schmidt, Hartmut H J

2016-01-01

 Amanita phalloides is the most relevant mushroom intoxication leading to acute liver failure. The two principal groups of toxins, the amatoxins and the phallotoxins, are small oligopeptides highly resistant to chemical and physical influences. The amatoxins inhibit eukaryotic RNA polymerase II causing transcription arrest affecting mainly metabolically highly active cells like hepatocytes and renal cells. The clinically most characteristic symptom is a 6-40 h lag phase before onset of gastrointestinal symptoms and the rapid progression of acute liver failure leading to multi-organ failure and death within a week if left untreated. Extracorporeal albumin dialysis (ECAD) was reported to improve patient's outcome or facilitate bridging to transplantation. In our tertiary center, out of nine intoxicated individuals from five non-related families six patients presented with acute liver injury; all of them were treated with ECAD using the MARS® system. Four of them were listed on admission for high urgency liver transplantation. In addition to standard medical treatment for Amanita intoxication we initiated ECAD once patients were admitted to our center. Overall 16 dialysis sessions were performed. All patients survived with full native liver recovery without the need for transplantation. ECAD was well tolerated; no severe adverse events were reported during treatment. Coagulopathy resolved within days in all patients, and acute kidney injury in all but one individual. In conclusion, ECAD is highly effective in treating intoxication with Amanita phalloides. Based on these experiences we suggest early initiation and repeated sessions depending on response to ECAD with the chance of avoiding liver transplantation.

Amyloid-β Peptide Exacerbates the Memory Deficit Caused by Amyloid Precursor Protein Loss-of-Function in Drosophila

PubMed Central

Bourdet, Isabelle; Lampin-Saint-Amaux, Aurélie; Preat, Thomas; Goguel, Valérie

2015-01-01

The amyloid precursor protein (APP) plays a central role in Alzheimer’s disease (AD). APP can undergo two exclusive proteolytic pathways: cleavage by the α-secretase initiates the non-amyloidogenic pathway while cleavage by the β-secretase initiates the amyloidogenic pathway that leads, after a second cleavage by the γ-secretase, to amyloid-β (Aβ) peptides that can form toxic extracellular deposits, a hallmark of AD. The initial events leading to AD are still unknown. Importantly, aside from Aβ toxicity whose molecular mechanisms remain elusive, several studies have shown that APP plays a positive role in memory, raising the possibility that APP loss-of-function may participate to AD. We previously showed that APPL, the Drosophila APP ortholog, is required for associative memory in young flies. In the present report, we provide the first analysis of the amyloidogenic pathway’s influence on memory in the adult. We show that transient overexpression of the β-secretase in the mushroom bodies, the center for olfactory memory, did not alter memory. In sharp contrast, β-secretase overexpression affected memory when associated with APPL partial loss-of-function. Interestingly, similar results were observed with Drosophila Aβ peptide. Because Aβ overexpression impaired memory only when combined to APPL partial loss-of-function, the data suggest that Aβ affects memory through the APPL pathway. Thus, memory is altered by two connected mechanisms—APPL loss-of-function and amyloid peptide toxicity—revealing in Drosophila a functional interaction between APPL and amyloid peptide. PMID:26274614

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

PubMed

Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

2017-05-10

Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

Household chemicals: management of intoxication and antidotes.

PubMed

Rauber-Lüthy, Christine; Kupferschmidt, Hugo

2010-01-01

Exposure to household products is very common, but in industrialized countries severe or fatal poisoning with household products is rare today, due to the legal restriction of sale of hazardous household products. The big challenge for physicians, pharmacologists and toxicologists is to identify the few exceptional life-threatening situations where immediate intervention is needed. Among thousands of innocuous products available for the household only very few are hazardous. Substances found in these products include detergents, corrosives, alcohols, hydrocarbons, and some of the essential oils. The ingestion of batteries and magnets and the exposure to cyanoacrylates (super glue) can cause complications in exceptional situations. Among the most dangerous substances still present in household products are ethylene glycol and methanol. These substances cause major toxicity only through their metabolites. Therefore, initial symptoms may be only mild or absent. Treatment even in asymptomatic patients has to be initiated as early as possible to inhibit production of toxic metabolites. For all substances not only the compound itself but also the route of exposure is relevant for toxicity. Oral ingestion and inhalation generally lead to most pronounced symptoms, while dermal exposure is often limited to mild irritation. However, certain circumstances need special attention. Exposure to hydrofluoric acid may lead to fatal hypocalcemia, depending on the concentration, duration of exposure, and area of the affected skin. Accidents with hydrocarbon pressure injectors and spray guns are very serious events, which may lead to amputation of affected limbs. Button batteries normally pass the gastrointestinal tract without problems even in toddlers; in rare cases, however, they get lodged in the esophagus with the risk of localized tissue damage and esophageal perforation.

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

PubMed Central

Sibmooh, Nathawut; Fucharoen, Suthat

2017-01-01

Abstract Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The βE-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794–813. PMID:27650096

Construction and Updating of Event Models in Auditory Event Processing

ERIC Educational Resources Information Center

Huff, Markus; Maurer, Annika E.; Brich, Irina; Pagenkopf, Anne; Wickelmaier, Florian; Papenmeier, Frank

2018-01-01

Humans segment the continuous stream of sensory information into distinct events at points of change. Between 2 events, humans perceive an event boundary. Present theories propose changes in the sensory information to trigger updating processes of the present event model. Increased encoding effort finally leads to a memory benefit at event…

Identification and characterization of ARS-like sequences as putative origin(s) of replication in human malaria parasite Plasmodium falciparum.

PubMed

Agarwal, Meetu; Bhowmick, Krishanu; Shah, Kushal; Krishnamachari, Annangarachari; Dhar, Suman Kumar

2017-08-01

DNA replication is a fundamental process in genome maintenance, and initiates from several genomic sites (origins) in eukaryotes. In Saccharomyces cerevisiae, conserved sequences known as autonomously replicating sequences (ARSs) provide a landing pad for the origin recognition complex (ORC), leading to replication initiation. Although origins from higher eukaryotes share some common sequence features, the definitive genomic organization of these sites remains elusive. The human malaria parasite Plasmodium falciparum undergoes multiple rounds of DNA replication; therefore, control of initiation events is crucial to ensure proper replication. However, the sites of DNA replication initiation and the mechanism by which replication is initiated are poorly understood. Here, we have identified and characterized putative origins in P. falciparum by bioinformatics analyses and experimental approaches. An autocorrelation measure method was initially used to search for regions with marked fluctuation (dips) in the chromosome, which we hypothesized might contain potential origins. Indeed, S. cerevisiae ARS consensus sequences were found in dip regions. Several of these P. falciparum sequences were validated with chromatin immunoprecipitation-quantitative PCR, nascent strand abundance and a plasmid stability assay. Subsequently, the same sequences were used in yeast to confirm their potential as origins in vivo. Our results identify the presence of functional ARSs in P. falciparum and provide meaningful insights into replication origins in these deadly parasites. These data could be useful in designing transgenic vectors with improved stability for transfection in P. falciparum. © 2017 Federation of European Biochemical Societies.

Formation of retinal direction-selective circuitry initiated by starburst amacrine cell homotypic contact

PubMed Central

Ray, Thomas A; Roy, Suva; Kozlowski, Christopher; Wang, Jingjing; Cafaro, Jon; Hulbert, Samuel W; Wright, Christopher V; Field, Greg D

2018-01-01

A common strategy by which developing neurons locate their synaptic partners is through projections to circuit-specific neuropil sublayers. Once established, sublayers serve as a substrate for selective synapse formation, but how sublayers arise during neurodevelopment remains unknown. Here, we identify the earliest events that initiate formation of the direction-selective circuit in the inner plexiform layer of mouse retina. We demonstrate that radially migrating newborn starburst amacrine cells establish homotypic contacts on arrival at the inner retina. These contacts, mediated by the cell-surface protein MEGF10, trigger neuropil innervation resulting in generation of two sublayers comprising starburst-cell dendrites. This dendritic scaffold then recruits projections from circuit partners. Abolishing MEGF10-mediated contacts profoundly delays and ultimately disrupts sublayer formation, leading to broader direction tuning and weaker direction-selectivity in retinal ganglion cells. Our findings reveal a mechanism by which differentiating neurons transition from migratory to mature morphology, and highlight this mechanism’s importance in forming circuit-specific sublayers. PMID:29611808

Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

PubMed

Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

2014-01-01

The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

Towards a global IT system for personalized medicine: the Medicine Safety Code initiative.

PubMed

Samwald, Matthias; Minarro-Giménez, José Antonio; Blagec, Kathrin; Adlassnig, Klaus-Peter

2014-01-01

The availability of pharmacogenomic data of individual patients can significantly improve physicians' prescribing behavior, lead to a reduced incidence of adverse drug events and an improvement of effectiveness of treatment. The Medicine Safety Code (MSC) initiative is an effort to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. The MSC is a standardized two-dimensional barcode that captures individual pharmacogenomic data. The system is backed by a web service that allows the decoding and interpretation of anonymous MSCs without requiring the installation of dedicated software. The system is based on a curated, ontology-based knowledge base representing pharmacogenomic definitions and clinical guidelines. The MSC system performed well in preliminary tests. To evaluate the system in realistic health care settings and to translate it into practical applications, the future participation of stakeholders in clinical institutions, medical researchers, pharmaceutical companies, genetic testing providers, health IT companies and health insurance organizations will be essential.

Predictability of horizontal water vapor transport relative to precipitation: Enhancing situational awareness for forecasting western U.S. extreme precipitation and flooding

USGS Publications Warehouse

Lavers, David A.; Waliser, Duane E.; Ralph, F. Martin; Dettinger, Michael

2016-01-01

The western United States is vulnerable to socioeconomic disruption due to extreme winter precipitation and floods. Traditionally, forecasts of precipitation and river discharge provide the basis for preparations. Herein we show that earlier event awareness may be possible through use of horizontal water vapor transport (integrated vapor transport (IVT)) forecasts. Applying the potential predictability concept to the National Centers for Environmental Prediction global ensemble reforecasts, across 31 winters, IVT is found to be more predictable than precipitation. IVT ensemble forecasts with the smallest spreads (least forecast uncertainty) are associated with initiation states with anomalously high geopotential heights south of Alaska, a setup conducive for anticyclonic conditions and weak IVT into the western United States. IVT ensemble forecasts with the greatest spreads (most forecast uncertainty) have initiation states with anomalously low geopotential heights south of Alaska and correspond to atmospheric rivers. The greater IVT predictability could provide warnings of impending storminess with additional lead times for hydrometeorological applications.

Pathways leading to an immunological disease: systemic lupus erythematosus.

PubMed

Zharkova, Olga; Celhar, Teja; Cravens, Petra D; Satterthwaite, Anne B; Fairhurst, Anna-Marie; Davis, Laurie S

2017-04-01

SLE is a chronic autoimmune disease caused by perturbations of the immune system. The clinical presentation is heterogeneous, largely because of the multiple genetic and environmental factors that contribute to disease initiation and progression. Over the last 60 years, there have been a number of significant leaps in our understanding of the immunological mechanisms driving disease processes. We now know that multiple leucocyte subsets, together with inflammatory cytokines, chemokines and regulatory mediators that are normally involved in host protection from invading pathogens, contribute to the inflammatory events leading to tissue destruction and organ failure. In this broad overview, we discuss the main pathways involved in SLE and highlight new findings. We describe the immunological changes that characterize this form of autoimmunity. The major leucocytes that are essential for disease progression are discussed, together with key mediators that propagate the immune response and drive the inflammatory response in SLE. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum

PubMed Central

Gao, Xiaohong; Gunalan, Karthigayan; Yap, Sally Shu Lin; Preiser, Peter R.

2013-01-01

Invasion of erythrocytes by Plasmodium falciparum merozoites is a complex multi-step process mediated by specific interactions between host receptors and parasite ligands. Reticulocyte-binding protein homologues (RHs) and erythrocyte-binding-like (EBL) proteins are discharged from specialized organelles and used in early steps of invasion. Here we show that monoclonal antibodies against PfRH1 (an RH) block merozoite invasion by specifically inhibiting calcium signalling in the parasite, whereas invasion-inhibiting monoclonal antibodies targeting EBA175 (an EBL protein) have no effect on signalling. We further show that inhibition of this calcium signalling prevents EBA175 discharge and thereby formation of the junction between parasite and host cell. Our results indicate that PfRH1 has an initial sensing as well as signal transduction role that leads to the subsequent release of EBA175. They also provide new insights on how RH–host cell interactions lead to essential downstream signalling events in the parasite, suggesting new targets for malaria intervention. PMID:24280897

Large Area Nondestructive Evaluation of a Fatigue Loaded Composite Structure

NASA Technical Reports Server (NTRS)

Zalameda, Joseph N.; Burke, Eric R.; Horne, Michael R.; Madaras, Eric I.

2016-01-01

Large area nondestructive evaluation (NDE) inspections are required for fatigue testing of composite structures to track damage initiation and growth. Of particular interest is the progression of damage leading to ultimate failure to validate damage progression models. In this work, passive thermography and acoustic emission NDE were used to track damage growth up to failure of a composite three-stringer panel. Fourteen acoustic emission sensors were placed on the composite panel. The signals from the array were acquired simultaneously and allowed for acoustic emission location. In addition, real time thermal data of the composite structure were acquired during loading. Details are presented on the mapping of the acoustic emission locations directly onto the thermal imagery to confirm areas of damage growth leading to ultimate failure. This required synchronizing the acoustic emission and thermal data with the applied loading. In addition, processing of the thermal imagery which included contrast enhancement, removal of optical barrel distortion and correction of angular rotation before mapping the acoustic event locations are discussed.

Meteoroid-bumper interactions program

NASA Technical Reports Server (NTRS)

Gough, P. S.

1970-01-01

An investigation has been made of the interaction of meteoroids with shielded structures. The interaction has been simulated by the impact of Lexan cylinders onto lead shields in order to provide the vaporous debris believed to be created by meteoroid impact on a space vehicle. Shock compression data for Lexan was determined. This, in combination with the known shock compression data for the lead shield, has permitted the definition of the initial high pressure states in the impacted projectile and shield. The debris from such impact events has been permitted to interact with aluminum main walls. The walls were chosen to be sufficiently large to be effectively infinite in diameter compared to the loaded area. The thickness of the wall and the spacing from the shield were varied to determine the effect of these parameters. In addition, the effect of having a body of water behind the wall has been assessed. Measurements of the stagnation pressure in the debris cloud have been made and correlated with the response of the main wall.

ARCUS Project Managers and the Intangible Infrastructure of Large Interdisciplinary Arctic Research Networks

NASA Astrophysics Data System (ADS)

Myers, B.; Wiggins, H. V.; Turner-Bogren, E. J.; Warburton, J.

2017-12-01

Project Managers at the Arctic Research Consortium of the U.S. (ARCUS) lead initiatives to convene, communicate with, and connect the Arctic research community across challenging disciplinary, geographic, temporal, and cultural boundaries. They regularly serve as the organizing hubs, archivists and memory-keepers for collaborative projects comprised of many loosely affiliated partners. As leading organizers of large open science meetings and other outreach events, they also monitor the interdisciplinary landscape of community needs, concerns, opportunities, and emerging research directions. However, leveraging the ARCUS Project Manager role to strategically build out the intangible infrastructure necessary to advance Arctic research requires a unique set of knowledge, skills, and experience. Drawing on a range of lessons learned from past and ongoing experiences with collaborative science, education and outreach programming, this presentation will highlight a model of ARCUS project management that we believe works best to support and sustain our community in its long-term effort to conquer the complexities of Arctic research.

Event-by-Event Fluctuations of Azimuthal Particle Anisotropy in Au+Au Collisions at sNN=200GeV

NASA Astrophysics Data System (ADS)

Alver, B.; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Busza, W.; Carroll, A.; Chai, Z.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Halliwell, C.; Hamblen, J.; Hauer, M.; Henderson, C.; Hofman, D. J.; Hollis, R. S.; Hołyński, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kulinich, P.; Kuo, C. M.; Li, W.; Lin, W. T.; Loizides, C.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Reed, C.; Roland, C.; Roland, G.; Sagerer, J.; Seals, H.; Sedykh, I.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Walters, P.; Wenger, E.; Wolfs, F. L. H.; Wosiek, B.; Woźniak, K.; Wysłouch, B.

2010-04-01

This Letter presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v2 in Au+Au collisions at sNN=200GeV as a function of collision centrality. The relative nonstatistical fluctuations of the v2 parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (nonflow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.

Productive Homologous and Non-homologous Recombination of Hepatitis C Virus in Cell Culture

PubMed Central

Li, Yi-Ping; Mikkelsen, Lotte S.; Gottwein, Judith M.; Bukh, Jens

2013-01-01

Genetic recombination is an important mechanism for increasing diversity of RNA viruses, and constitutes a viral escape mechanism to host immune responses and to treatment with antiviral compounds. Although rare, epidemiologically important hepatitis C virus (HCV) recombinants have been reported. In addition, recombination is an important regulatory mechanism of cytopathogenicity for the related pestiviruses. Here we describe recombination of HCV RNA in cell culture leading to production of infectious virus. Initially, hepatoma cells were co-transfected with a replicating JFH1ΔE1E2 genome (genotype 2a) lacking functional envelope genes and strain J6 (2a), which has functional envelope genes but does not replicate in culture. After an initial decrease in the number of HCV positive cells, infection spread after 13–36 days. Sequencing of recovered viruses revealed non-homologous recombinants with J6 sequence from the 5′ end to the NS2–NS3 region followed by JFH1 sequence from Core to the 3′ end. These recombinants carried duplicated sequence of up to 2400 nucleotides. HCV replication was not required for recombination, as recombinants were observed in most experiments even when two replication incompetent genomes were co-transfected. Reverse genetic studies verified the viability of representative recombinants. After serial passage, subsequent recombination events reducing or eliminating the duplicated region were observed for some but not all recombinants. Furthermore, we found that inter-genotypic recombination could occur, but at a lower frequency than intra-genotypic recombination. Productive recombination of attenuated HCV genomes depended on expression of all HCV proteins and tolerated duplicated sequence. In general, no strong site specificity was observed. Non-homologous recombination was observed in most cases, while few homologous events were identified. A better understanding of HCV recombination could help identification of natural recombinants and thereby lead to improved therapy. Our findings suggest mechanisms for occurrence of recombinants observed in patients. PMID:23555245

Relationship between history of coronary heart disease at dialysis initiation and onset of events associated with heart disease: a propensity-matched analysis of a prospective cohort study.

PubMed

Inaguma, Daijo; Koide, Shigehisa; Takahashi, Kazuo; Hayashi, Hiroki; Hasegawa, Midori; Yuzawa, Yukio

2017-02-28

Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease (CVD) events, and a number of reports have shown a relationship between CKD and CVD in pre-dialysis or maintenance dialysis patients. However, few studies have reported serial observations during dialysis initiation and maintenance. Therefore, we examined whether the incidence of heart disease events differed between CKD patients with and without a history of coronary heart disease (CHD) at dialysis initiation. The subjects were patients in the 17 centers participating in the Aichi Cohort Study of Prognosis in Patients Newly Initiated into Dialysis (AICOPP) from October 2011 to September 2013. We excluded nine patients whose outcomes were unknown, as determined by a survey conducted at the end of March 2015. Thus, we enrolled 1,515 subjects into the study. We classified patients into 2 groups according to the history of CHD (i.e., a CHD group and a non-CHD group). Propensity scores (PS) represented the probability of being assigned to a group with or without a history of CHD. Onset of heart disease events and associated mortality and all-cause mortality were compared in PS-matched patients by using the log-rank test for Kaplan-Meier curves. Factors contributing to heart disease events were examined using stepwise multivariate Cox proportional hazards analysis. There were 254 patients in each group after PS-matching. During observation, heart disease events occurred in 85 patients (33.5%) in the CHD group and 48 (18.9%) patients in the non-CHD group. The incidence was significantly higher in the CHD group (p < 0.0001). The CHD group was associated with higher incidence of heart disease events (vs. the non-CHD group, hazard ratio = 1.750, 95% confidence interval = 1.160-2.639). In addition, comorbidities such as diabetes mellitus, low body mass index, and low serum high-density lipoprotein cholesterol were associated with higher incidence of events. History of CHD at dialysis initiation was associated with a higher incidence of heart disease events and mortality and all-cause mortality. UMIN 000007096 . Registered 18 January 2012.

Event Segmentation Improves Event Memory up to One Month Later

ERIC Educational Resources Information Center

Flores, Shaney; Bailey, Heather R.; Eisenberg, Michelle L.; Zacks, Jeffrey M.

2017-01-01

When people observe everyday activity, they spontaneously parse it into discrete meaningful events. Individuals who segment activity in a more normative fashion show better subsequent memory for the events. If segmenting events effectively leads to better memory, does asking people to attend to segmentation improve subsequent memory? To answer…

Detection of back-to-back proton pairs in charged-current neutrino interactions with the ArgoNeuT detector in the NuMI low energy beam line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acciarri, R.; Adams, C.; Asaadi, J.

2014-07-01

Short range nucleon-nucleon correlations in nuclei (NN SRC) carry important information on nuclear structure and dynamics. NN SRC have been extensively probed through two-nucleon knock- out reactions in both pion and electron scattering experiments. We report here on the detection of two-nucleon knock-out events from neutrino interactions and discuss their topological features as possibly involving NN SRC content in the target argon nuclei. The ArgoNeuT detector in the Main Injector neutrino beam at Fermilab has recorded a sample of 30 fully reconstructed charged current events where the leading muon is accompanied by a pair of protons at the interaction vertex,more » 19 of which have both protons above the Fermi momentum of the Ar nucleus. Out of these 19 events, four are found with the two protons in a strictly back-to-back high momenta configuration directly observed in the final state and can be associated to nucleon Resonance pionless mechanisms involving a pre-existing short range correlated np pair in the nucleus. Another fraction (four events) of the remaining 15 events have a reconstructed back-to-back configuration of a np pair in the initial state, a signature compatible with one-body Quasi Elastic interaction on a neutron in a SRC pair. The detection of these two subsamples of the collected (mu- + 2p) events suggests that mechanisms directly involving nucleon-nucleon SRC pairs in the nucleus are active and can be efficiently explored in neutrino-argon interactions with the LAr TPC technology.« less

New early warning system for gravity-driven ruptures based on codetection of acoustic signal

NASA Astrophysics Data System (ADS)

Faillettaz, J.

2016-12-01

Gravity-driven rupture phenomena in natural media - e.g. landslide, rockfalls, snow or ice avalanches - represent an important class of natural hazards in mountainous regions. To protect the population against such events, a timely evacuation often constitutes the only effective way to secure the potentially endangered area. However, reliable prediction of imminence of such failure events remains challenging due to the nonlinear and complex nature of geological material failure hampered by inherent heterogeneity, unknown initial mechanical state, and complex load application (rainfall, temperature, etc.). Here, a simple method for real-time early warning that considers both the heterogeneity of natural media and characteristics of acoustic emissions attenuation is proposed. This new method capitalizes on codetection of elastic waves emanating from microcracks by multiple and spatially separated sensors. Event-codetection is considered as surrogate for large event size with more frequent codetected events (i.e., detected concurrently on more than one sensor) marking imminence of catastrophic failure. Simple numerical model based on a Fiber Bundle Model considering signal attenuation and hypothetical arrays of sensors confirms the early warning potential of codetection principles. Results suggest that although statistical properties of attenuated signal amplitude could lead to misleading results, monitoring the emergence of large events announcing impeding failure is possible even with attenuated signals depending on sensor network geometry and detection threshold. Preliminary application of the proposed method to acoustic emissions during failure of snow samples has confirmed the potential use of codetection as indicator for imminent failure at lab scale. The applicability of such simple and cheap early warning system is now investigated at a larger scale (hillslope). First results of such a pilot field experiment are presented and analysed.

The economic and clinical burden of early versus late initiation of celecoxib among patients with osteoarthritis

PubMed Central

Shelbaya, Ahmed; Solem, Caitlyn T; Walker, Chris; Wan, Yin; Johnson, Courtney; Cappelleri, Joseph C

2018-01-01

Objective This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib. Methods Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009–2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators. Results Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P<0.001) and OA-related (US$4,988 versus US$5,178, P=0.015) costs per person-year. Early initiators had no statistically significant difference in the incidence of post-celecoxib cardiovascular (IRR: 0.92; 95% CI: 0.73, 1.14), gastrointestinal (IRR: 1.25; 95% CI: 0.81, 1.92), or renal (IRR: 1.19; 95% CI: 0.65, 2.18) events, controlling for pre-index event rates and covariates when compared to late initiators. Conclusion In this real-world cohort, patients initiated on celecoxib early (versus late) had significantly lower costs and HCRU; this may warrant consideration when making treatment decisions for OA patients. PMID:29670383

PROGRESS TOWARDS NEXT GENERATION, WAVEFORM BASED THREE-DIMENSIONAL MODELS AND METRICS TO IMPROVE NUCLEAR EXPLOSION MONITORING IN THE MIDDLE EAST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Savage, B; Peter, D; Covellone, B

2009-07-02

Efforts to update current wave speed models of the Middle East require a thoroughly tested database of sources and recordings. Recordings of seismic waves traversing the region from Tibet to the Red Sea will be the principal metric in guiding improvements to the current wave speed model. Precise characterizations of the earthquakes, specifically depths and faulting mechanisms, are essential to avoid mapping source errors into the refined wave speed model. Errors associated with the source are manifested in amplitude and phase changes. Source depths and paths near nodal planes are particularly error prone as small changes may severely affect themore » resulting wavefield. Once sources are quantified, regions requiring refinement will be highlighted using adjoint tomography methods based on spectral element simulations [Komatitsch and Tromp (1999)]. An initial database of 250 regional Middle Eastern events from 1990-2007, was inverted for depth and focal mechanism using teleseismic arrivals [Kikuchi and Kanamori (1982)] and regional surface and body waves [Zhao and Helmberger (1994)]. From this initial database, we reinterpreted a large, well recorded subset of 201 events through a direct comparison between data and synthetics based upon a centroid moment tensor inversion [Liu et al. (2004)]. Evaluation was done using both a 1D reference model [Dziewonski and Anderson (1981)] at periods greater than 80 seconds and a 3D model [Kustowski et al. (2008)] at periods of 25 seconds and longer. The final source reinterpretations will be within the 3D model, as this is the initial starting point for the adjoint tomography. Transitioning from a 1D to 3D wave speed model shows dramatic improvements when comparisons are done at shorter periods, (25 s). Synthetics from the 1D model were created through mode summations while those from the 3D simulations were created using the spectral element method. To further assess errors in source depth and focal mechanism, comparisons between the three methods were made. These comparisons help to identify problematic stations and sources which may bias the final solution. Estimates of standard errors were generated for each event's source depth and focal mechanism to identify poorly constrained events. A final, well characterized set of sources and stations will be then used to iteratively improve the wave speed model of the Middle East. After a few iterations during the adjoint inversion process, the sources will be reexamined and relocated to further reduce mapping of source errors into structural features. Finally, efforts continue in developing the infrastructure required to 'quickly' generate event kernels at the n-th iteration and invert for a new, (n+1)-th, wave speed model of the Middle East. While development of the infrastructure proceeds, initial tests using a limited number of events shows the 3D model, while showing vast improvement compared to the 1D model, still requires substantial modifications. Employing our new, full source set and iterating the adjoint inversions at successively shorter periods will lead to significant changes and refined wave speed structures of the Middle East.« less

Clinical course of 63 patients with neonatal onset urea cycle disorders in the years 2001-2013.

PubMed

Unsinn, Caroline; Das, Anibh; Valayannopoulos, Vassili; Thimm, Eva; Beblo, Skadi; Burlina, Alberto; Konstantopoulou, Vassiliki; Mayorandan, Sebene; de Lonlay, Pascale; Rennecke, Jörg; Derbinski, Jens; Hoffmann, Georg F; Häberle, Johannes

2016-08-19

Urea cycle disorders (UCDs) are rare inherited metabolic defects of ammonia detoxification. In about half of patients presenting with a UCD, the first symptoms appear within a few days after birth. These neonatal onset patients generally have a severe defect of urea cycle function and their survival and outcome prognoses are often limited. To understand better the current situation of neonatal onset in UCDs, we have performed a multicentre, retrospective, non-interventional case series study focussing on the most severe UCDs, namely defects of carbamoyl phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthetase (ASS). Data of 63 patients were collected (27 patients with ASS deficiency, 23 patients with OTC deficiency, and 12 patients with CPS1 deficiency, one patient definite diagnosis not documented). The majority of patients (43/63, 68 %) had an initial ammonia concentration exceeding 500 μmol/L (normal < 100), of which most (26/43, 60.5 %) were also encephalopathic and were treated with hemodialysis. In patients surviving the initial crisis, recurrence of hyperammonemic events within the first 1.5 years of life occurred frequently (mean 3.6 events, range 0-20). Of all patients, 16 (25.4 %) died during or immediately after the neonatal period. We observed in this cohort of neonatal onset UCD patients a high rate of initial life-threatening hyperammonemia and a high risk of recurrence of severe hyperammonemic crises. These corresponded to a high mortality rate during the entire study period (30.2 %) despite the fact that patients were treated in leading European metabolic centers. This underlines the need to critically re-evaluate the current treatment strategies in these patients.

Determinants of initiation and progression of idiopathic pulmonary fibrosis

PubMed Central

Kottmann, Robert Matthew; Hogan, Christopher M.; Phipps, Richard P.; Sime, Patricia J.

2013-01-01

IPF is a devastating disease with few therapeutic options. The precise aetiology of IPF remains elusive. However, our understanding of the pathologic processes involved in the initiation and progression of this disease is improving. Data on the mechanisms underlying IPF have been generated from epidemiologic investigations as well as cellular and molecular studies of human tissues. Although no perfect animal model of human IPF exists, pre-clinical animal studies have helped define pathways which are likely important in human disease. Epithelial injury, fibroblast activation and repetitive cycles of injury and abnormal repair are almost certainly key events. Factors which have been associated with initiation and/or progression of IPF include viral infections, abnormal cytokine, chemokine and growth factor production, oxidant stress, autoimmunity, inhalational of toxicants and gastro-oesophageal reflux disease. Furthermore, recent evidence identifies a role for a variety of genetic and epigenetic abnormalities ranging from mutations in surfactant protein C to abnormalities in telomere length and telomerase activity. The challenge remains to identify additional inciting agents and key dysregulated pathways that lead to disease progression so that we can develop targeted therapies to treat or prevent this serious disease. PMID:19740254

Changes in Smoking Behavior over Family Transitions: Evidence for Anticipation and Adaptation Effects.

PubMed

Bricard, Damien; Legleye, Stéphane; Khlat, Myriam

2017-06-07

The study of changes in smoking behaviors over the life course is a promising line of research. This paper aims to analyze the temporal relation between family transitions (partnership formation, first childbirth, separation) and changes in smoking initiation and cessation. We propose a discrete-time logistic model to explore the timing of changes in terms of leads and lags effects up to three years around the event in order to measure both anticipation and adaptation mechanisms. Retrospective biographical data from the Santé et Itinéraires Professionnels (SIP) survey conducted in France in 2006 are used. Partnership formation was followed for both genders by a fall in smoking initiation and an immediate rise in smoking cessation. Childbirth was associated with increased smoking cessation immediately around childbirth, and additionally, females showed an anticipatory increase in smoking cessation up to two years before childbirth. Couple separation was accompanied by an anticipatory increase in smoking initiation for females up to two years prior to the separation, but this effect only occurred in males during separation. Our findings highlight opportunities for more targeted interventions over the life course to reduce smoking, and therefore have relevance for general practitioners and public policy elaboration.

Platelets in thrombosis and hemostasis: old topic with new mechanisms.

PubMed

Wang, Yiming; Andrews, Marc; Yang, Yan; Lang, Sean; Jin, Joseph W; Cameron-Vendrig, Alison; Zhu, Guangheng; Reheman, Adili; Ni, Heyu

2012-12-01

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. After being released into the circulation, platelets play key roles in the surveillance of vascular injury, and can quickly adhere and aggregate at the site of injury, which are critical events for vascular repair and hemostasis. However, the same biological processes of platelet adhesion and aggregation may also cause thrombotic disorders. The formation of a platelet plug at sites of atherosclerotic lesion rupture is the most common mechanism leading to myocardial or cerebral infarction. Platelet-related deep vein thrombosis is also one of the leading causes of mortality worldwide. The contribution of several platelet receptors and their ligands has been highlighted in these processes. In platelet adhesion, particularly at high shear stress, GPIbα-von Willebrand factor (VWF) interaction may initiate this event, which is followed by GPVI signalling and firm platelet adhesion mediated by members of the integrin family, such as β3 (αIIbβ3) and β1 (α2β1, α5β1) integrins. In platelet aggregation, although GPIbα-VWF, P selectin-sulfatides, and other molecules, may be involved, the process is mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as fibrinogen and VWF. It is intriguing that platelet adhesion and aggregation still occur in mice lacking both fibrinogen and VWF, suggesting that other unforeseen molecule(s) may also be important in these processes. Identification and characterization of these molecules will enrich our knowledge in the basic science of hemostasis and thrombosis, and may lead to the development of new therapies against bleeding disorders and thrombotic diseases.

Coalescence of repelling colloidal droplets: a route to monodisperse populations.

PubMed

Roger, Kevin; Botet, Robert; Cabane, Bernard

2013-05-14

Populations of droplets or particles dispersed in a liquid may evolve through Brownian collisions, aggregation, and coalescence. We have found a set of conditions under which these populations evolve spontaneously toward a narrow size distribution. The experimental system consists of poly(methyl methacrylate) (PMMA) nanodroplets dispersed in a solvent (acetone) + nonsolvent (water) mixture. These droplets carry electrical charges, located on the ionic end groups of the macromolecules. We used time-resolved small angle X-ray scattering to determine their size distribution. We find that the droplets grow through coalescence events: the average radius (R) increases logarithmically with elapsed time while the relative width σR/(R) of the distribution decreases as the inverse square root of (R). We interpret this evolution as resulting from coalescence events that are hindered by ionic repulsions between droplets. We generalize this evolution through a simulation of the Smoluchowski kinetic equation, with a kernel that takes into account the interactions between droplets. In the case of vanishing or attractive interactions, all droplet encounters lead to coalescence. The corresponding kernel leads to the well-known "self-preserving" particle distribution of the coalescence process, where σR/(R) increases to a plateau value. However, for droplets that interact through long-range ionic repulsions, "large + small" droplet encounters are more successful at coalescence than "large + large" encounters. We show that the corresponding kernel leads to a particular scaling of the droplet-size distribution-known as the "second-scaling law" in the theory of critical phenomena, where σR/(R) decreases as 1/√(R) and becomes independent of the initial distribution. We argue that this scaling explains the narrow size distributions of colloidal dispersions that have been synthesized through aggregation processes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek

Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potentialmore » and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant potential or both.« less

ASN reputation system model

NASA Astrophysics Data System (ADS)

Hutchinson, Steve; Erbacher, Robert F.

2015-05-01

Network security monitoring is currently challenged by its reliance on human analysts and the inability for tools to generate indications and warnings for previously unknown attacks. We propose a reputation system based on IP address set membership within the Autonomous System Number (ASN) system. Essentially, a metric generated based on the historic behavior, or misbehavior, of nodes within a given ASN can be used to predict future behavior and provide a mechanism to locate network activity requiring inspection. This will provide reinforcement of notifications and warnings and lead to inspection for ASNs known to be problematic even if initial inspection leads to interpretation of the event as innocuous. We developed proof of concept capabilities to generate the IP address to ASN set membership and analyze the impact of the results. These results clearly show that while some ASNs are one-offs with individual or small numbers of misbehaving IP addresses, there are definitive ASNs with a history of long term and wide spread misbehaving IP addresses. These ASNs with long histories are what we are especially interested in and will provide an additional correlation metric for the human analyst and lead to new tools to aid remediation of these IP address blocks.

The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

PubMed Central

Famakin, Bolanle M.

2014-01-01

It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke. PMID:25276490

Physical modelling of tsunamis generated by three-dimensional deformable granular landslides on planar and conical island slopes

PubMed Central

2016-01-01

Tsunamis generated by landslides and volcanic island collapses account for some of the most catastrophic events recorded, yet critically important field data related to the landslide motion and tsunami evolution remain lacking. Landslide-generated tsunami source and propagation scenarios are physically modelled in a three-dimensional tsunami wave basin. A unique pneumatic landslide tsunami generator was deployed to simulate landslides with varying geometry and kinematics. The landslides were generated on a planar hill slope and divergent convex conical hill slope to study lateral hill slope effects on the wave characteristics. The leading wave crest amplitude generated on a planar hill slope is larger on average than the leading wave crest generated on a convex conical hill slope, whereas the leading wave trough and second wave crest amplitudes are smaller. Between 1% and 24% of the landslide kinetic energy is transferred into the wave train. Cobble landslides transfer on average 43% more kinetic energy into the wave train than corresponding gravel landslides. Predictive equations for the offshore propagating wave amplitudes, periods, celerities and lengths generated by landslides on planar and divergent convex conical hill slopes are derived, which allow an initial rapid tsunami hazard assessment. PMID:27274697

Physical modelling of tsunamis generated by three-dimensional deformable granular landslides on planar and conical island slopes.

PubMed

McFall, Brian C; Fritz, Hermann M

2016-04-01

Tsunamis generated by landslides and volcanic island collapses account for some of the most catastrophic events recorded, yet critically important field data related to the landslide motion and tsunami evolution remain lacking. Landslide-generated tsunami source and propagation scenarios are physically modelled in a three-dimensional tsunami wave basin. A unique pneumatic landslide tsunami generator was deployed to simulate landslides with varying geometry and kinematics. The landslides were generated on a planar hill slope and divergent convex conical hill slope to study lateral hill slope effects on the wave characteristics. The leading wave crest amplitude generated on a planar hill slope is larger on average than the leading wave crest generated on a convex conical hill slope, whereas the leading wave trough and second wave crest amplitudes are smaller. Between 1% and 24% of the landslide kinetic energy is transferred into the wave train. Cobble landslides transfer on average 43% more kinetic energy into the wave train than corresponding gravel landslides. Predictive equations for the offshore propagating wave amplitudes, periods, celerities and lengths generated by landslides on planar and divergent convex conical hill slopes are derived, which allow an initial rapid tsunami hazard assessment.

Correlating Transcription Initiation and Conformational Changes by a Single-Subunit RNA Polymerase with Near Base-Pair Resolution.

PubMed

Koh, Hye Ran; Roy, Rahul; Sorokina, Maria; Tang, Guo-Qing; Nandakumar, Divya; Patel, Smita S; Ha, Taekjip

2018-05-17

We provide a comprehensive analysis of transcription in real time by T7 RNA Polymerase (RNAP) using single-molecule fluorescence resonance energy transfer by monitoring the entire life history of transcription initiation, including stepwise RNA synthesis with near base-pair resolution, abortive cycling, and transition into elongation. Kinetically branching pathways were observed for abortive initiation with an RNAP either recycling on the same promoter or exchanging with another RNAP from solution. We detected fast and slow populations of RNAP in their transition into elongation, consistent with the efficient and delayed promoter release, respectively, observed in ensemble studies. Real-time monitoring of abortive cycling using three-probe analysis showed that the initiation events are stochastically branched into productive and failed transcription. The abortive products are generated primarily from initiation events that fail to progress to elongation, and a majority of the productive events transit to elongation without making abortive products. Copyright © 2018 Elsevier Inc. All rights reserved.

Early warning of orographically induced floods and landslides in Western Norway

NASA Astrophysics Data System (ADS)

Leine, Ann-Live; Wang, Thea; Boje, Søren

2017-04-01

In Western Norway, landslides and debris flows are commonly initiated by short-term orographic rainfall or intensity peaks during a prolonged rainfall event. In recent years, the flood warning service in Norway has evolved from being solely a flood forecasting service to also integrating landslides into its early warning systems. As both floods and landslides are closely related to the same hydrometeorological processes, particularly in small catchments, there is a natural synergy between monitoring flood and landslide risk. The Norwegian Flood and Landslide Hazard Forecasting and Warning Service issues regional landslide hazard warnings based on hydrological models, threshold values, observations and weather forecasts. Intense rainfall events and/or orographic precipitation that, under certain topographic conditions, significantly increase the risk of debris avalanches and debris floods are lately receiving more research focus from the Norwegian warning service. Orographic precipitation is a common feature in W-Norway, when moist and relatively mild air arrives from the Atlantic. Steep mountain slopes covered by glacial till makes the region prone to landslides, as well as flooding. The operational early warning system in Norway requires constant improvement, especially with the enhanced number of intense rainfall events that occur in a warming climate. Here, we examine different cases of intense rainfall events which have lead to landslides and debris flows, as well as increased runoff in fast responding small catchments. The main objective is to increase the understanding of the hydrometeorological conditions related to these events, in order to make priorities for the future development of the warning service.

Abrupt state change of river water quality (turbidity): Effect of extreme rainfalls and typhoons.

PubMed

Lee, Chih-Sheng; Lee, Yi-Chao; Chiang, Hui-Min

2016-07-01

River turbidity is of dynamic nature, and its stable state is significantly changed during the period of heavy rainfall events. The frequent occurrence of typhoons in Taiwan has caused serious problems in drinking water treatment due to extremely high turbidity. The aim of the present study is to evaluate impact of typhoons on river turbidity. The statistical methods used included analyses of paired annual mean and standard deviation, frequency distribution, and moving standard deviation, skewness, and autocorrelation; all clearly indicating significant state changes of river turbidity. Typhoon Morakot of 2009 (recorded high rainfall over 2000mm in three days, responsible for significant disaster in southern Taiwan) is assumed as a major initiated event leading to critical state change. In addition, increasing rate of turbidity in rainfall events is highly and positively correlated with rainfall intensity both for pre- and post-Morakot periods. Daily turbidity is also well correlated with daily flow rate for all the eleven events evaluated. That implies potential prediction of river turbidity by river flow rate during rainfall and typhoon events. Based on analysis of stable state changes, more effective regulations for better basin management including soil-water conservation in watershed are necessary. Furthermore, municipal and industrial water treatment plants need to prepare and ensure the adequate operation of water treatment with high raw water turbidity (e.g., >2000NTU). Finally, methodology used in the present of this study can be applied to other environmental problems with abrupt state changes. Copyright © 2016 Elsevier B.V. All rights reserved.

Extreme Events and Disaster Risk Reduction - a Future Earth KAN initiative

NASA Astrophysics Data System (ADS)

Frank, Dorothea; Reichstein, Markus

2017-04-01

The topic of Extreme Events in the context of global environmental change is both a scientifically challenging and exciting topic, and of very high societal relevance. The Future Earth Cluster initiative E3S organized in 2016 a cross-community/co-design workshop on Extreme Events and Environments from Climate to Society (http://www.e3s-future-earth.eu/index.php/ConferencesEvents/ConferencesAmpEvents). Based on the results, co-design research strategies and established network of the workshop, and previous activities, E3S is thriving to establish the basis for a longer-term research effort under the umbrella of Future Earth. These led to an initiative for a Future Earth Knowledge Action Network on Extreme Events and Disaster Risk Reduction. Example initial key question in this context include: What are meaningful indices to describe and quantify impact-relevant (e.g. climate) extremes? Which system properties yield resistance and resilience to extreme conditions? What are the key interactions between global urbanization processes, extreme events, and social and infrastructure vulnerability and resilience? The long-term goal of this KAN is to contribute to enhancing the resistance, resilience, and adaptive capacity of socio-ecological systems across spatial, temporal and institutional scales, in particular in the light of hazards affected by ongoing environmental change (e.g. climate change, global urbanization and land use/land cover change). This can be achieved by enhanced understanding, prediction, improved and open data and knowledge bases for detection and early warning decision making, and by new insights on natural and societal conditions and governance for resilience and adaptive capacity.

Sub-seasonal prediction of significant wave heights over the Western Pacific and Indian Oceans, part II: The impact of ENSO and MJO

NASA Astrophysics Data System (ADS)

Shukla, Ravi P.; Kinter, James L.; Shin, Chul-Su

2018-03-01

This study evaluates the effect of El Niño and the Southern Oscillation (ENSO) and Madden Julian Oscillation (MJO) events on 14-day mean significant wave height (SWH) at 3 weeks lead time (Wk34) over the Western Pacific and Indian Oceans using the National Centers for Environmental Prediction (NCEP) Climate Forecast System, version 2 (CFSv2). The WAVEWATCH-3 (WW3) model is forced with daily 10m-winds predicted by a modified version of CFSv2 that is initialized with multiple ocean analyses in both January and May for 1979-2008. A significant anomaly correlation of predicted and observed SWH anomalies (SWHA) at Wk34 lead-time is found over portions of the domain, including the central western Pacific, South China Sea (SCS), Bay of Bengal (BOB) and southern Indian Ocean (IO) in January cases, and over BOB, equatorial western Pacific, the Maritime Continent and southern IO in May cases. The model successfully predicts almost all the important features of the observed composite SWHA during El Niño events in January, including negative SWHA in the central IO where westerly wind anomalies act on an easterly mean state, and positive SWHA over the southern Ocean (SO) where westerly wind anomalies act on a westerly mean state. The model successfully predicts the sign and magnitude of SWHA at Wk34 lead-time in May over the BOB and SCS in composites of combined phases-2-3 and phases-6-7 of MJO. The observed leading mode of SWHA in May and the third mode of SWHA in January are influenced by the combined effects of ENSO and MJO. Based on spatial and temporal correlations, the spatial patterns of SWHA in the model at Wk34 in both January and May are in good agreement with the observations over the equatorial western Pacific, equatorial and southern IO, and SO.

A Synoptic Climatology of Combined Severe/Weather/Flash Flood Events

NASA Astrophysics Data System (ADS)

Pallozzi, Kyle J.

Classical forms of severe weather such as tornadoes, damaging convective wind gusts, and large hail, as well as flash flooding events, all have potentially large societal impacts. This impact is further magnified when these hazards occur simultaneously in time and space. A major challenge for operational forecasters is how to accurately predict the occurrence of combined storm hazards, and how to communicate the associated multiple threat hazards to the public. A seven-year climatology (2009-2015) of combined severe weather/flash flooding (SVR/FF) events across the contiguous United States was developed in attempt to study the combined SVR/FF event hazards further. A total of 211 total cases were identified and sub-divided into seven subcategories based on their convective morphology and meteorological characteristics. Heatmaps of event report frequency were created to extract spatial, seasonal and interannual patterns in SVR/FF event activity. Diurnal trends were examined from time series plots of tornado, hail, wind and flash flood/flood reports. Event-centered composites of environmental variables were created for each subcategory from 13 km RUC/RAP analyses. Representative cases studies were conducted for each subcategory. A "ring of fire" with the highest levels of SVR/FF event activity was noted across the central United States. SVR/FF events were least common in the Southeast, High Plains, and Northern Plains. Enhanced SVR/FF activity reflected contributions from synoptic events during the cool and shoulder seasons over the Lower Mississippi, Arkansas and Tennessee Valleys, and MCS activity during the warm season over the lower Great Plains, and the Upper Mississippi, Missouri and Ohio River Valleys. Results from the composite analyses indicated that relatively high values of CAPE, surface-500 hPa shear and precipitable water were observed for all subcategories. Case studies show that many high-end SVR/FF events featured slow-moving, or quasi-stationary fronts/outflow boundaries, a moist troposphere and front-paralleling 850-300 hPa mean winds. In this environment, individual convective cells can be advected downstream along the initiating boundary, resulting in flood-producing training echoes. A relatively moist troposphere leads to efficient precipitation production, limits cold-pool formation/off-boundary propagation, and further increases the likelihood of flash flooding.

RAVEN Theory Manual

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfonsi, Andrea; Rabiti, Cristian; Mandelli, Diego

2016-06-01

RAVEN is a software framework able to perform parametric and stochastic analysis based on the response of complex system codes. The initial development was aimed at providing dynamic risk analysis capabilities to the thermohydraulic code RELAP-7, currently under development at Idaho National Laboratory (INL). Although the initial goal has been fully accomplished, RAVEN is now a multi-purpose stochastic and uncertainty quantification platform, capable of communicating with any system code. In fact, the provided Application Programming Interfaces (APIs) allow RAVEN to interact with any code as long as all the parameters that need to be perturbed are accessible by input filesmore » or via python interfaces. RAVEN is capable of investigating system response and explore input space using various sampling schemes such as Monte Carlo, grid, or Latin hypercube. However, RAVEN strength lies in its system feature discovery capabilities such as: constructing limit surfaces, separating regions of the input space leading to system failure, and using dynamic supervised learning techniques. The development of RAVEN started in 2012 when, within the Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, the need to provide a modern risk evaluation framework arose. RAVEN’s principal assignment is to provide the necessary software and algorithms in order to employ the concepts developed by the Risk Informed Safety Margin Characterization (RISMC) program. RISMC is one of the pathways defined within the Light Water Reactor Sustainability (LWRS) program. In the RISMC approach, the goal is not just to identify the frequency of an event potentially leading to a system failure, but the proximity (or lack thereof) to key safety-related events. Hence, the approach is interested in identifying and increasing the safety margins related to those events. A safety margin is a numerical value quantifying the probability that a safety metric (e.g. peak pressure in a pipe) is exceeded under certain conditions. Most of the capabilities, implemented having RELAP-7 as a principal focus, are easily deployable to other system codes. For this reason, several side activates have been employed (e.g. RELAP5-3D, any MOOSE-based App, etc.) or are currently ongoing for coupling RAVEN with several different software. The aim of this document is to provide a set of commented examples that can help the user to become familiar with the RAVEN code usage.« less

Analysis of Effects of Sensor Multithreading to Generate Local System Event Timelines

DTIC Science & Technology

2014-03-27

works on logs highlights the importance of logs [17, 18]. The two aforementioned works both reference the same 2009 Data Breach Investigations Report...the data breaches report on, the logs contained evidence of events leading up to 82% of those data breaches . This means that preventing 82% of the data ...report states that of the data breaches reported on, the logs contained evidence of events leading up to 66% of those data breaches . • The 2010 DBIR

Long-Term Major Clinical Outcomes in Patients With Long Chain Fatty Acid Oxidation Disorders Before and After Transition to Triheptanoin Treatment—A Retrospective Chart Review

PubMed Central

Vockley, Jerry; Marsden, Deborah; McCracken, Elizabeth; DeWard, Stephanie; Barone, Amanda; Hsu, Kristen; Kakkis, Emil

2015-01-01

Background Long chain fatty acid oxidation disorders (LC-FAOD) are caused by defects in the metabolic pathway that converts stored long-chain fatty acids into energy, leading to a deficiency in mitochondrial energy production during times of physiologic stress and fasting. Severe and potentially life threatening clinical manifestations include rhabdomyolysis, hypoglycemia, hypotonia/weakness, cardiomyopathy and sudden death. We present the largest cohort of patients to date treated with triheptanoin, a specialized medium odd chain (C7) triglyceride, as a novel energy source for the treatment of LC-FAOD. Methods This was a retrospective, comprehensive medical record review study of data from 20 of a total 24 patients with LC-FAOD who were treated for up to 12.5 years with triheptanoin, as part of a compassionate use protocol. Clinical outcomes including hospitalization event rates, number of hospitalization days/year, and abnormal laboratory values were determined for the total period of the study before and after triheptanoin treatment, as well as for specified periods before and after initiation of triheptanoin treatment. Other events of interest were documented including rhabdomyolysis, hypoglycemia, and cardiomyopathy. Results LC-FAOD in these 20 subjects was associated with 320 hospitalizations from birth to the end date of study. The mean hospitalization days/year decreased significantly by 67% during the period after triheptanoin initiation (n=15; 5.76 vs 17.55 vs; P=0.0242) and a trend toward a 35% lower hospitalization event rate was observed in the period after triheptanoin initiation compared with the before-treatment period (n=16 subjects >6 months of age; 1.26 vs 1.94; P=0.1126). The hypoglycemia event rate per year in 9 subjects with hypoglycemia problems declined significantly by 96% (0.04 vs 0.92; P=0.0091) and related hospitalization days/year were also significantly reduced (n=9; 0.18 vs 8.42; P=0.0257). The rhabdomyolysis hospital event rate in 11 affected subjects was similar before and after treatment but the number of hospitalization days/year trended lower in the period after triheptanoin initiation (n=9; 2.36 vs 5.94; P=0.1224) and peak CK levels trended toward a 68% decrease from 85,855 to 27,597 units in 7 subjects with reported peak CK values before and after treatment (P=0.1279). Triheptanoin was generally well tolerated. Gastrointestinal symptoms were the most commonly reported side effects. Conclusions This retrospective study represents the largest analysis reported to date of treatment of LC-FAOD with triheptanoin. The data suggest that triheptanoin improves the course of disease by decreasing the incidence and duration of major clinical manifestations and should be the focus of prospective investigations. Significant heterogeneity in the routine clinical care provided to subjects during the periods studied and the natural variation of clinical course of LC-FAODs with time emphasize the need additioanl study of the use of triheptanoin. PMID:26116311

An assessment of calcite crystal growth mechanisms based on crystal size distributions

USGS Publications Warehouse

Kile, D.E.; Eberl, D.D.; Hoch, A.R.; Reddy, M.M.

2000-01-01

Calcite crystal growth experiments were undertaken to test a recently proposed model that relates crystal growth mechanisms to the shapes of crystal size distributions (CSDs). According to this approach, CSDs for minerals have three basic shapes: (1) asymptotic, which is related to a crystal growth mechanism having constant-rate nucleation accompanied by surface-controlled growth; (2) lognormal, which results from decaying-rate nucleation accompanied by surface-controlled growth; and (3) a theoretical, universal, steady-state curve attributed to Ostwald ripening. In addition, there is a fourth crystal growth mechanism that does not have a specific CSD shape, but which preserves the relative shapes of previously formed CSDs. This mechanism is attributed to supply-controlled growth. All three shapes were produced experimentally in the calcite growth experiments by modifying nucleation conditions and solution concentrations. The asymptotic CSD formed when additional reactants were added stepwise to the surface of solutions that were supersaturated with respect to calcite (initial Ω = 20, where Ω = 1 represents saturation), thereby leading to the continuous nucleation and growth of calcite crystals. Lognormal CSDs resulted when reactants were added continuously below the solution surface, via a submerged tube, to similarly supersaturated solutions (initial Ω = 22 to 41), thereby leading to a single nucleation event followed by surface-controlled growth. The Ostwald CSD resulted when concentrated reactants were rapidly mixed, leading initially to high levels of supersaturation (Ω >100), and to the formation and subsequent dissolution of very small nuclei, thereby yielding CSDs having small crystal size variances. The three CSD shapes likely were produced early in the crystallization process, in the nanometer crystal size range, and preserved during subsequent growth. Preservation of the relative shapes of the CSDs indicates that a supply-controlled growth mechanism was established and maintained during the constant-composition experiments. CSDs having shapes intermediate between lognormal and Ostwald also were generated by varying the initial levels of supersaturation (initial Ω = 28.2 to 69.2) in rapidly mixed solutions. Lognormal CSDs were observed for natural calcite crystals that are found in septarian concretions occurring in southeastern Colorado. Based on the model described above, these CSDs indicate initial growth by surface control, followed by supply-controlled growth. Thus, CSDs may be used to deduce crystal growth mechanisms from which geologic conditions early in the growth history of a mineral can be inferred. Conversely, CSD shape can be predicted during industrial crystallization by applying the appropriate conditions for a particular growth mechanism.

Longitudinal confocal microscopy imaging of solid tumor destruction following adoptive T cell transfer

PubMed Central

Schietinger, Andrea; Arina, Ainhoa; Liu, Rebecca B; Wells, Sam; Huang, Jianhua; Engels, Boris; Bindokas, Vytas; Bartkowiak, Todd; Lee, David; Herrmann, Andreas; Piston, David W; Pittet, Mikael J; Lin, P Charles; Zal, Tomasz; Schreiber, Hans

2013-01-01

A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells—all color-coded in vivo—was analyzed in established, solid tumors that had developed behind windows implanted on the backs of mice. Events could be followed repeatedly within precisely the same tumor region—before, during and after adoptive T cell therapy—thereby enabling for the first time a longitudinal in vivo evaluation of protracted events, an analysis not possible with terminal imaging of surgically exposed tumors. T cell infiltration, stromal interactions, and vessel destruction, as well as the functional consequences thereof, including the elimination of cancer cells and cancer cell variants were studied. Minimal perivascular T cell infiltrates initiated vascular destruction inside the tumor mass eventually leading to macroscopic central tumor necrosis. Prolonged engagement of T cells with tumor antigen-crosspresenting stromal cells correlated with high IFNγ cytokine release and bystander elimination of antigen-negative cancer cells. The high-resolution, longitudinal, in vivo imaging approach described here will help to further a better mechanistic understanding of tumor eradication by T cells and other anti-cancer therapies. PMID:24482750

Sensitivity of El Niño intensity and timing to preceding subsurface heat magnitude

PubMed Central

Ballester, Joan; Petrova, Desislava; Bordoni, Simona; Ben Cash; García-Díez, Markel; Rodó, Xavier

2016-01-01

Despite extensive ongoing efforts on improving the long-term prediction of El Niño-Southern Oscillation, the predictability in state-of-the-art operational schemes remains limited by factors such as the spring barrier and the influence of atmospheric winds. Recent research suggests that the 2014/15 El Niño (EN) event was stalled as a result of an unusually strong basin-wide easterly wind burst in June, which led to the discharge of a large fraction of the subsurface ocean heat. Here we use observational records and numerical experiments to explore the sensitivity of EN to the magnitude of the heat buildup occurring in the ocean subsurface 21 months in advance. Our simulations suggest that a large increase in heat content during this phase can lead to basin-wide uniform warm conditions in the equatorial Pacific the winter before the occurrence of a very strong EN event. In our model configuration, the system compensates any initial decrease in heat content and naturally evolves towards a new recharge, resulting in a delay of up to one year in the occurrence of an EN event. Both scenarios substantiate the non-linear dependency between the intensity of the subsurface heat buildup and the magnitude and timing of subsequent EN episodes. PMID:27808279

Sensitivity of El Niño intensity and timing to preceding subsurface heat magnitude.

PubMed

Ballester, Joan; Petrova, Desislava; Bordoni, Simona; Ben Cash; García-Díez, Markel; Rodó, Xavier

2016-11-03

Despite extensive ongoing efforts on improving the long-term prediction of El Niño-Southern Oscillation, the predictability in state-of-the-art operational schemes remains limited by factors such as the spring barrier and the influence of atmospheric winds. Recent research suggests that the 2014/15 El Niño (EN) event was stalled as a result of an unusually strong basin-wide easterly wind burst in June, which led to the discharge of a large fraction of the subsurface ocean heat. Here we use observational records and numerical experiments to explore the sensitivity of EN to the magnitude of the heat buildup occurring in the ocean subsurface 21 months in advance. Our simulations suggest that a large increase in heat content during this phase can lead to basin-wide uniform warm conditions in the equatorial Pacific the winter before the occurrence of a very strong EN event. In our model configuration, the system compensates any initial decrease in heat content and naturally evolves towards a new recharge, resulting in a delay of up to one year in the occurrence of an EN event. Both scenarios substantiate the non-linear dependency between the intensity of the subsurface heat buildup and the magnitude and timing of subsequent EN episodes.

Environmental triggers in IBD: a review of progress and evidence.

PubMed

Ananthakrishnan, Ashwin N; Bernstein, Charles N; Iliopoulos, Dimitrios; Macpherson, Andrew; Neurath, Markus F; Ali, Raja A Raja; Vavricka, Stephan R; Fiocchi, Claudio

2018-01-01

A number of environmental factors have been associated with the development of IBD. Alteration of the gut microbiota, or dysbiosis, is closely linked to initiation or progression of IBD, but whether dysbiosis is a primary or secondary event is unclear. Nevertheless, early-life events such as birth, breastfeeding and exposure to antibiotics, as well as later childhood events, are considered potential risk factors for IBD. Air pollution, a consequence of the progressive contamination of the environment by countless compounds, is another factor associated with IBD, as particulate matter or other components can alter the host's mucosal defences and trigger immune responses. Hypoxia associated with high altitude is also a factor under investigation as a potential new trigger of IBD flares. A key issue is how to translate environmental factors into mechanisms of IBD, and systems biology is increasingly recognized as a strategic tool to unravel the molecular alterations leading to IBD. Environmental factors add a substantial level of complexity to the understanding of IBD pathogenesis but also promote the fundamental notion that complex diseases such as IBD require complex therapies that go well beyond the current single-agent treatment approach. This Review describes the current conceptualization, evidence, progress and direction surrounding the association of environmental factors with IBD.

AMOS Galaxy 15 Satellite Observations and Analysis

NASA Astrophysics Data System (ADS)

Hall, D.

2011-09-01

In early April 2010, the Galaxy 15 geosynchronous satellite experienced an on-orbit anomaly. Even though the satellite's transmitters and articulating solar panel were still functioning, ground controllers lost the ability to command and maneuver the satellite. With its orbital position no longer maintained, Galaxy 15 began to drift eastward. This forced several other satellites to make collision avoidance maneuvers during the following months. Soon after the initial anomaly, Galaxy 15's operators predicted that the satellite’s reaction wheels would eventually become saturated, causing a loss of both spacecraft attitude and proper sunward orientation of the solar panels. This "off-pointing" event finally occurred in late December, ultimately leading to a depletion of Galaxy 15's batteries. This near-death experience had a fortunate side effect, however, in that it forced the satellite’s command unit to reboot and once again be able to both receive and execute ground commands. The satellite operators have since recovered control of the satellite. AMOS conducted non-resolved photometric observations of Galaxy 15 before, during and after these events. Similar observations were conducted of Galaxy 12, the nearly-identical replacement satellite. This presentation presents and discusses these temporal brightness signatures in detail, comparing the changing patterns in the observations to the known sequence of events.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aad, G.

The four-lepton (4ℓ , ℓ=e,μℓ=e,μ) production cross section is measured in the mass range from 80 to 1000 GeV using 20.3 fb -1 of data in pp collisions at √s=8 TeV collected with the ATLAS detector at the LHC. The 4ℓ events are produced in the decays of resonant Z and Higgs bosons and the non-resonant ZZ continuum originating from View the MathML sourceqq¯, gg, and qg initial states. A total of 476 signal candidate events are observed with a background expectation of 26.2±3.626.2±3.6 events, enabling the measurement of the integrated cross section and the differential cross section as amore » function of the invariant mass and transverse momentum of the four-lepton system. In the mass range above 180 GeV, assuming the theoretical constraint on the View the MathML sourceqq¯ production cross section calculated with perturbative NNLO QCD and NLO electroweak corrections, the signal strength of the gluon-fusion component relative to its leading-order prediction is determined to be μ gg=2.4±1.0 (stat.)±0.5 (syst.)±0.8 (theory)μ gg=2.4±1.0 (stat.)±0.5 (syst.)±0.8 (theory).« less

Life on Mars - How it disappeared (if it was ever there)

NASA Technical Reports Server (NTRS)

Friedmann, E. Imre; Koriem, Ali M.

1989-01-01

Information available on Mars chemistry suggest that conditions on early Mars may have been suitable for life. This paper examines the possible events that led to the disappearance of life, assuming it existed, from the surface of Mars. The sequence of events leading to life extinction on early Mars assumes the following steps: (1) a decrease of temperature and humidity levels, leading to a selection of microorganisms for tolerance of low temperatures and arid conditions; (2) further deterioration of environment leading to withdrawal of cold-adapted organisms to protected niches under the surface; (3) further cooling producing heavy stresses in these organisms; and (4) further deterioration of the environment resulting in extinction. This sequence of events is considered parallel events documented for the microbial community in the Ross Desert of Antarctica, where TEM examinations of the material detected progressive stages of cell damage and death.

News Conference: The Big Bangor Day Meeting Lecture: Charterhouse plays host to a physics day Festival: Science on Stage festival 2013 arrives in Poland Event: Scottish Physics Teachers' Summer School Meeting: Researchers and educators meet at Lund University Conference: Exeter marks the spot Recognition: European Physical Society uncovers an historic site Education: Initial teacher education undergoes big changes Forthcoming events

NASA Astrophysics Data System (ADS)

2013-09-01

Conference: The Big Bangor Day Meeting Lecture: Charterhouse plays host to a physics day Festival: Science on Stage festival 2013 arrives in Poland Event: Scottish Physics Teachers' Summer School Meeting: Researchers and educators meet at Lund University Conference: Exeter marks the spot Recognition: European Physical Society uncovers an historic site Education: Initial teacher education undergoes big changes Forthcoming events

A novel kinase regulates dietary restriction-mediated longevity in Caenorhabditis elegans

PubMed Central

Chamoli, Manish; Singh, Anupama; Malik, Yasir; Mukhopadhyay, Arnab

2014-01-01

Although dietary restriction (DR) is known to extend lifespan across species, from yeast to mammals, the signalling events downstream of food/nutrient perception are not well understood. In Caenorhabditis elegans, DR is typically attained either by using the eat-2 mutants that have reduced pharyngeal pumping leading to lower food intake or by feeding diluted bacterial food to the worms. In this study, we show that knocking down a mammalian MEKK3-like kinase gene, mekk-3 in C. elegans, initiates a process similar to DR without compromising food intake. This DR-like state results in upregulation of beta-oxidation genes through the nuclear hormone receptor NHR-49, a HNF-4 homolog, resulting in depletion of stored fat. This metabolic shift leads to low levels of reactive oxygen species (ROS), potent oxidizing agents that damage macromolecules. Increased beta-oxidation, in turn, induces the phase I and II xenobiotic detoxification genes, through PHA-4/FOXA, NHR-8 and aryl hydrocarbon receptor AHR-1, possibly to purge lipophilic endotoxins generated during fatty acid catabolism. The coupling of a metabolic shift with endotoxin detoxification results in extreme longevity following mekk-3 knock-down. Thus, MEKK-3 may function as an important nutrient sensor and signalling component within the organism that controls metabolism. Knocking down mekk-3 may signal an imminent nutrient crisis that results in initiation of a DR-like state, even when food is plentiful. PMID:24655420

Fear of driving license withdrawal in patients with insulin-treated diabetes mellitus negatively influences their decision to report severe hypoglycemic events to physicians.

PubMed

Brož, Jan; Brabec, Marek; Janíčková Žďárská, Denisa; Fedáková, Zuzana; Hoskovcová, Lucie; You, Jee Young; Doničová, Viera; Hlaďo, Petr; Rahelić, Dario; Kvapil, Milan; Polák, Jan

2015-01-01

Under current European Union legislation, two severe hypoglycemic events within 12 months is grounds for driving license withdrawal. The aim of the study reported here was to determine whether fear of such a withdrawal could lead to patients concealing severe hypoglycemia from physicians, which could negatively impact further treatment decisions. A total of 663 patients with insulin-treated diabetes were anonymously surveyed about whether they would conceal severe hypoglycemic events from their physicians, if revealing them could result in driving license withdrawal. This investigation utilized an adapted and expanded questionnaire by Graveling et al. Of all diabetic patients surveyed, 26.17% would most likely not report hypoglycemia, and 25.86% were undecided. In a group of patients with type 1 diabetes, 31.83% would likely not report hypoglycemic events, and 25.06% were undecided. The patients least likely to report severe hypoglycemic events were those who indicated that vehicles were partly essential for work, and who also had more than two hypoglycemic events monthly. A considerable percentage of diabetic patients would likely conceal severe hypoglycemic events from their physicians due to fear of driving license withdrawal. Patient failure to report severe hypoglycemic events can potentially lead to physicians being misinformed regarding the patient's condition, which could lead to inadequate monitoring and treatment.

External events analysis for the Savannah River Site K reactor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brandyberry, M.D.; Wingo, H.E.

1990-01-01

The probabilistic external events analysis performed for the Savannah River Site K-reactor PRA considered many different events which are generally perceived to be external'' to the reactor and its systems, such as fires, floods, seismic events, and transportation accidents (as well as many others). Events which have been shown to be significant contributors to risk include seismic events, tornados, a crane failure scenario, fires and dam failures. The total contribution to the core melt frequency from external initiators has been found to be 2.2 {times} 10{sup {minus}4} per year, from which seismic events are the major contributor (1.2 {times} 10{supmore » {minus}4} per year). Fire initiated events contribute 1.4 {times} 10{sup {minus}7} per year, tornados 5.8 {times} 10{sup {minus}7} per year, dam failures 1.5 {times} 10{sup {minus}6} per year and the crane failure scenario less than 10{sup {minus}4} per year to the core melt frequency. 8 refs., 3 figs., 5 tabs.« less

A Retrospective Analysis of Corticosteroid Utilization Before Initiation of Biologic DMARDs Among Patients with Rheumatoid Arthritis in the United States.

PubMed

Spivey, Christina A; Griffith, Jenny; Kaplan, Cameron; Postlethwaite, Arnold; Ganguli, Arijit; Wang, Junling

2018-06-01

Understanding the effects of corticosteroid utilization prior to initiation of biologic disease-modifying antirheumatic drugs (DMARDs) can inform decision-makers on the appropriate use of these medications. This study examined treatment patterns and associated burden of corticosteroid utilization before initiation of biologic DMARDs among rheumatoid arthritis (RA) patients. A retrospective analysis was conducted of adult RA patients in the US MarketScan Database (2011-2015). The following patterns of corticosteroid utilization were analyzed: whether corticosteroids were used; duration of use (short/long duration defined as < or ≥ 3 months); and dosage (low as < 2.5, medium as 2.5 to < 7.5 and high as ≥ 7.5 mg/day). Effects of corticosteroid use on time to biologic DMARD initiation were examined using Cox proportional hazards models. Likelihood and number of adverse events were examined using logistic and negative binomial regression models. Generalized linear models were used to examine healthcare costs. Independent variables in all models included patient demographics and health characteristics. A total of 25,542 patients were included (40.84% used corticosteroids). Lower hazard of biologic DMARD initiation was associated with corticosteroid use (hazard ratio = 0.89, 95% confidence interval = 0.83-0.96), long duration and lower dose. Corticosteroid users compared to non-users had higher incidence rates of various adverse events including cardiovascular events (P < 0.05). Higher likelihood of adverse events was associated with corticosteroid use and long duration of use, as was increased number of adverse events. Corticosteroid users had a greater annualized mean number of physician visits, hospitalizations, and emergency department (ED) visits than non-users in adjusted analysis. Corticosteroid users compared to non-users had higher mean costs for total healthcare, physician visits, hospitalizations, and ED visits. Among patients with RA, corticosteroid utilization is associated with delayed initiation of biologic DMARDS and higher burden of adverse events and healthcare utilization/costs before the initiation of biologic DMARDs. AbbVie Inc.

On the origin of heavy-tail statistics in equations of the Nonlinear Schrödinger type

NASA Astrophysics Data System (ADS)

Onorato, Miguel; Proment, Davide; El, Gennady; Randoux, Stephane; Suret, Pierre

2016-09-01

We study the formation of extreme events in incoherent systems described by the Nonlinear Schrödinger type of equations. We consider an exact identity that relates the evolution of the normalized fourth-order moment of the probability density function of the wave envelope to the rate of change of the width of the Fourier spectrum of the wave field. We show that, given an initial condition characterized by some distribution of the wave envelope, an increase of the spectral bandwidth in the focusing/defocusing regime leads to an increase/decrease of the probability of formation of rogue waves. Extensive numerical simulations in 1D+1 and 2D+1 are also performed to confirm the results.

Meiosis, unreduced gametes, and parthenogenesis: implications for engineering clonal seed formation in crops.

PubMed

Ronceret, Arnaud; Vielle-Calzada, Jean-Philippe

2015-06-01

Meiosis and unreduced gametes. Sexual flowering plants produce meiotically derived cells that give rise to the male and female haploid gametophytic phase. In the ovule, usually a single precursor (the megaspore mother cell) undergoes meiosis to form four haploid megaspores; however, numerous mutants result in the formation of unreduced gametes, sometimes showing female specificity, a phenomenon reminiscent of the initiation of gametophytic apomixis. Here, we review the developmental events that occur during female meiosis and megasporogenesis at the light of current possibilities to engineer unreduced gamete formation. We also provide an overview of the current understanding of mechanisms leading to parthenogenesis and discuss some of the conceptual implications for attempting the induction of clonal seed production in cultivated plants.

Comparison of algorithms for the detection of cancer-drivers at sub-gene resolution

PubMed Central

Porta-Pardo, Eduard; Kamburov, Atanas; Tamborero, David; Pons, Tirso; Grases, Daniela; Valencia, Alfonso; Lopez-Bigas, Nuria; Getz, Gad; Godzik, Adam

2018-01-01

Understanding genetic events that lead to cancer initiation and progression remains one of the biggest challenges in cancer biology. Traditionally most algorithms for cancer driver identification look for genes that have more mutations than expected from the average background mutation rate. However, there is now a wide variety of methods that look for non-random distribution of mutations within proteins as a signal they have a driving role in cancer. Here we classify and review the progress of such sub-gene resolution algorithms, compare their findings on four distinct cancer datasets from The Cancer Genome Atlas and discuss how predictions from these algorithms can be interpreted in the emerging paradigms that challenge the simple dichotomy between driver and passenger genes. PMID:28714987

TNF-induced necroptosis requires the plasma membrane localization of the MLKL protein | Center for Cancer Research

Cancer.gov

The cell signaling protein tumor necrosis factor (TNF), produced by white blood cells, promotes inflammation and immunity processes such as fever and is involved in tumorigenesis and apoptosis (programmed cell death). However, dysregulation of TNF can also lead to another form of programmed cell death called necroptosis, which is characterized by a rise in intracellular Ca2+, generation of reactive oxygen species (ROS), intracellular acidity, depletion of ATP, and, eventually, plasma membrane rupture. TNF-induced necroptosis has been associated with a wide variety of diseases including neurodegenerative diseases, major depression, rheumatoid arthritis, and cancer. Whereas the signaling mechanisms underlying TNF-induced apoptosis have largely been determined, the events precipitating in TNF-initiated necroptosis are still unknown.

Chromatin Constrains the Initiation and Elongation of DNA Replication.

PubMed

Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

2017-01-05

Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

PubMed Central

Carayol, Nathalie; Tran Van Nhieu, Guy

2013-01-01

As opposed to other invasive pathogens that reside into host cells in a parasitic mode, Shigella, the causative agent of bacillary dysentery, invades the colonic mucosa but does not penetrate further to survive into deeper tissues. Instead, Shigella invades, replicates, and disseminates within the colonic mucosa. Bacterial invasion and spreading in intestinal epithelium lead to the elicitation of inflammatory responses responsible for the tissue destruction and shedding in the environment for further infection of other hosts. In this article, we highlight specific features of the Shigella arsenal of virulence determinants injected by a type III secretion apparatus (T3SA) that point to the targeting of intestinal epithelial cells as a discrete route of invasion during the initial event of the infectious process. PMID:24086068

Examining live cell cultures during apoptosis by digital holographic phase imaging and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Khmaladze, Alexander

2017-11-01

Cellular apoptosis is a unique, organized series of events, leading to programmed cell death. In this work, we present a combined digital holography/Raman spectroscopy technique to study live cell cultures during apoptosis. Digital holographic microscopy measurements of live cell cultures yield information about cell shape and volume, changes to which are indicative of alterations in cell cycle and initiation of cell death mechanisms. Raman spectroscopic measurements provide complementary information about cells, such as protein, lipid and nucleic acid content, and the spectral signatures associated with structural changes in molecules. Our work indicates that the chemical changes in proteins, which were detected by Raman measurements, preceded morphological changes, which were seen with digital holographic microscopy.

Genomic and epigenomic regulation of adipose tissue inflammation in obesity.

PubMed

Toubal, Amine; Treuter, Eckardt; Clément, Karine; Venteclef, Nicolas

2013-12-01

Chronic inflammation of adipose tissue is viewed as a hallmark of obesity and contributes to the development of type 2 diabetes and cardiovascular disease. According to current models, nutrient excess causes metabolic and structural changes in adipocytes, which initiate transcriptional programs leading to the expression of inflammatory molecules and the subsequent recruitment of immune cells. Recent advances in deciphering the underlying mechanisms revealed that key regulatory events occur at the genomic and epigenomic levels. Here we review these advances because they offer a better understanding of the mechanisms behind the complex obesogenic program in adipose tissue, and because they may help in defining new therapeutic strategies that prevent, restrict, and resolve inflammation in the context of obesity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Methods for external event screening quantification: Risk Methods Integration and Evaluation Program (RMIEP) methods development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ravindra, M.K.; Banon, H.

1992-07-01

In this report, the scoping quantification procedures for external events in probabilistic risk assessments of nuclear power plants are described. External event analysis in a PRA has three important goals; (1) the analysis should be complete in that all events are considered; (2) by following some selected screening criteria, the more significant events are identified for detailed analysis; (3) the selected events are analyzed in depth by taking into account the unique features of the events: hazard, fragility of structures and equipment, external-event initiated accident sequences, etc. Based on the above goals, external event analysis may be considered as amore » three-stage process: Stage I: Identification and Initial Screening of External Events; Stage II: Bounding Analysis; Stage III: Detailed Risk Analysis. In the present report, first, a review of published PRAs is given to focus on the significance and treatment of external events in full-scope PRAs. Except for seismic, flooding, fire, and extreme wind events, the contributions of other external events to plant risk have been found to be negligible. Second, scoping methods for external events not covered in detail in the NRC's PRA Procedures Guide are provided. For this purpose, bounding analyses for transportation accidents, extreme winds and tornadoes, aircraft impacts, turbine missiles, and chemical release are described.« less

Unsteady Aerodynamic Simulations of a Finned Projectile at a Supersonic Speed With Jet Interaction

DTIC Science & Technology

2014-06-01

20 4.4 Transient Effects During the Jet Event and Time-Accuracy of...35 Figure 27. Transient effects of jet maneuver event for the no initial angular...rate case. ................36 Figure 28. Effect of time step on the coupled solution for the initial low roll rate case: (a) roll rate, (b) roll angle

A three-tiered approach for linking pharmacokinetic considerations to the adverse outcome pathway framework for chemical-specific risk assessment

EPA Science Inventory

The power of the adverse outcome pathway (AOP) framework arises from its utilization of pathway-based data to describe the initial interaction of a chemical with a molecular target (molecular initiating event; (MIE), followed by a progression through a series of key events that l...

On the relative role of meridional convergence and downwelling motion during the heat buildup leading to El Niño events

NASA Astrophysics Data System (ADS)

Ballester, Joan; Bordoni, Simona; Petrova, Desislava; Rodó, Xavier

2015-04-01

Despite steady progress in the understanding of El Niño-Southern Oscillation (ENSO) in the past decades, questions remain on the exact mechanisms leading to the onset of El Niño (EN) events. Several authors have highlighted how the subsurface heat buildup in the western tropical Pacific and the recharged phase in equatorial heat content are intrinsic elements of ENSO variability, leading to those changes in zonal wind stress, sea surface temperature and thermocline tilt that characterize the growing and mature phases of EN. Here we use an ensemble of ocean and atmosphere assimilation products to identify the mechanisms contributing to the heat buildup that precedes EN events by about 18-24 months on average. Anomalous equatorward subsurface mass convergence due to meridional Sverdrup transport is found to be an important mechanism of thermocline deepening near and to the east of the dateline. In the warm pool, instead, surface horizontal convergence and downwelling motion have a leading role in subsurface warming, since equatorward mass convergence is weaker and counterbalanced by subsurface zonal divergence. The picture emerging from our results highlights the complexity of the three dimensional dynamic and thermodynamic structure of the tropical Pacific during the heat buildup leading to EN events.

Differences in alarm events between disposable and reusable electrocardiography lead wires.

PubMed

Albert, Nancy M; Murray, Terri; Bena, James F; Slifcak, Ellen; Roach, Joel D; Spence, Jackie; Burkle, Alicia

2015-01-01

Disposable electrocardiographic lead wires (ECG-LWs) may not be as durable as reusable ones. To examine differences in alarm events between disposable and reusable ECG-LWs. Two cardiac telemetry units were randomized to reusable ECG-LWs, and 2 units alternated between disposable and reusable ECG-LWs for 4 months. A remote monitoring team, blinded to ECG-LW type, assessed frequency and type of alarm events by using total counts and rates per 100 patient days. Event rates were compared by using generalized linear mixed-effect models for differences and noninferiority between wire types. In 1611 patients and 9385.5 patient days of ECG monitoring, patient characteristics were similar between groups. Rates of alarms for no telemetry, leads fail, or leads off were lower in disposable ECG-LWs (adjusted relative risk [95% CI], 0.71 [0.53-0.96]; noninferiority P < .001; superiority P = .03) and monitoring (artifact) alarms were significantly noninferior (adjusted relative risk [95% CI]: 0.88, [0.62-1.24], P = .02; superiority P = .44). No between-group differences existed in false or true crisis alarms. Disposable ECG-LWs were noninferior to reusable ECG-LWs for all false-alarm events (N [rate per 100 patient days], disposable 2029 [79.1] vs reusable 6673 [97.9]; adjusted relative risk [95% CI]: 0.81 [0.63-1.06], P = .002; superiority P = .12.) Disposable ECG-LWs with patented push-button design had superior performance in reducing alarms created by no telemetry, leads fail, or leads off and significant noninferiority in all false-alarm rates compared with reusable ECG-LWs. Fewer ECG alarms may save nurses time, decrease alarm fatigue, and improve patient safety. ©2015 American Association of Critical-Care Nurses.