A SAS-based solution to evaluate study design efficiency of phase I pediatric oncology trials via discrete event simulation.

PubMed

Barrett, Jeffrey S; Jayaraman, Bhuvana; Patel, Dimple; Skolnik, Jeffrey M

2008-06-01

Previous exploration of oncology study design efficiency has focused on Markov processes alone (probability-based events) without consideration for time dependencies. Barriers to study completion include time delays associated with patient accrual, inevaluability (IE), time to dose limiting toxicities (DLT) and administrative and review time. Discrete event simulation (DES) can incorporate probability-based assignment of DLT and IE frequency, correlated with cohort in the case of DLT, with time-based events defined by stochastic relationships. A SAS-based solution to examine study efficiency metrics and evaluate design modifications that would improve study efficiency is presented. Virtual patients are simulated with attributes defined from prior distributions of relevant patient characteristics. Study population datasets are read into SAS macros which select patients and enroll them into a study based on the specific design criteria if the study is open to enrollment. Waiting times, arrival times and time to study events are also sampled from prior distributions; post-processing of study simulations is provided within the decision macros and compared across designs in a separate post-processing algorithm. This solution is examined via comparison of the standard 3+3 decision rule relative to the "rolling 6" design, a newly proposed enrollment strategy for the phase I pediatric oncology setting.

Exploration of a Preflight Acuity Scale for Fixed Wing Air Ambulance Transport.

PubMed

Phipps, Marcy; Conley, Virginia; Constantine, William H

Despite the prevalence of fixed wing medical flights for specialized care and repatriation, few acuity rating scales exist aimed at the prediction of adverse in-flight medical events. An acuity scoring system can provide information to flight crews, allowing for staffing enhancements, protocol modifications, and flight planning, with the aim of improving patient care, outcomes, and preventing losses to providers because of costly diversions. Our medical crew developed an acuity scale, which was applied retrospectively to 296 patients transported between January 2016 and March 2017. Patients received scores based on conditions identified during the preflight medical report, the initial patient assessment, demographics, and flight factors. Five patients were identified as high-risk transports based on our scale. Three patients suffered adverse events according to our defined criteria, 2 of which occurred before transport and 1 during transport. The 3 patients suffering adverse events did not receive a score that indicated adverse events in flight. Our scale was not predictive of adverse events in flight. However, it did illuminate factors worthy of consideration. Consideration of these factors may have prevented adverse events. Published by Elsevier Inc.

mRNA Traffic Control Reviewed: N6-Methyladenosine (m6 A) Takes the Driver's Seat.

PubMed

Visvanathan, Abhirami; Somasundaram, Kumaravel

2018-01-01

Messenger RNA is a flexible tool box that plays a key role in the dynamic regulation of gene expression. RNA modifications variegate the message conveyed by the mRNA. Similar to DNA and histone modifications, mRNA modifications are reversible and play a key role in the regulation of molecular events. Our understanding about the landscape of RNA modifications is still rudimentary in contrast to DNA and histone modifications. The major obstacle has been the lack of sensitive detection methods since they are non-editing events. However, with the advent of next-generation sequencing techniques, RNA modifications are being identified precisely at single nucleotide resolution. In recent years, methylation at the N6 position of adenine (m 6 A) has gained the attention of RNA biologists. The m 6 A modification has a set of writers (methylases), erasers (demethylases), and readers. Here, we provide a summary of interesting facts, conflicting findings, and recent advances in the technical and functional aspects of the m 6 A epitranscriptome. © 2017 WILEY Periodicals, Inc.

Optimized methods of chromatin immunoprecipitation for profiling histone modifications in industrial microalgae Nannochloropsis spp.

PubMed

Wei, Li; Xu, Jian

2018-06-01

Epigenetic factors such as histone modifications play integral roles in plant development and stress response, yet their implications in algae remain poorly understood. In the industrial oleaginous microalgae Nannochloropsis spp., the lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which determines the specific genomic location of various histone modifications, has hindered probing the epigenetic basis of their photosynthetic carbon conversion and storage as oil. Here, a detailed ChIP protocol was developed for Nannochloropsis oceanica, which represents a reliable approach for the analysis of histone modifications, chromatin state, and transcription factor-binding sites at the epigenetic level. Using ChIP-qPCR, genes related to photosynthetic carbon fixation in this microalga were systematically assessed. Furthermore, a ChIP-Seq protocol was established and optimized, which generated a genome-wide profile of histone modification events, using histone mark H3K9Ac as an example. These results are the first step for appreciation of the chromatin landscape in industrial oleaginous microalgae and for epigenetics-based microalgal feedstock development. © 2018 Phycological Society of America.

Measurement of D-meson production versus multiplicity in p-Pb collisions at √{{s}_{NN}}=5.02 TeV

NASA Astrophysics Data System (ADS)

Adam, J.; Adamová, D.; Aggarwal, M. M.; Aglieri Rinella, G.; Agnello, M.; Agrawal, N.; Ahammed, Z.; Ahn, S. U.; Aiola, S.; Akindinov, A.; Alam, S. N.; Aleksandrov, D.; Alessandro, B.; Alexandre, D.; Alfaro Molina, R.; Alici, A.; Alkin, A.; Almaraz, J. R. M.; Alme, J.; Alt, T.; Altinpinar, S.; Altsybeev, I.; Alves Garcia Prado, C.; Andrei, C.; Andronic, A.; Anguelov, V.; Anielski, J.; Antičić, T.; Antinori, F.; Antonioli, P.; Aphecetche, L.; Appelshäuser, H.; Arcelli, S.; Arnaldi, R.; Arnold, O. W.; Arsene, I. C.; Arslandok, M.; Audurier, B.; Augustinus, A.; Averbeck, R.; Azmi, M. D.; Badalà, A.; Baek, Y. W.; Bagnasco, S.; Bailhache, R.; Bala, R.; Balasubramanian, S.; Baldisseri, A.; Baral, R. C.; Barbano, A. M.; Barbera, R.; Barile, F.; Barnaföldi, G. G.; Barnby, L. S.; Barret, V.; Bartalini, P.; Barth, K.; Bartke, J.; Bartsch, E.; Basile, M.; Bastid, N.; Basu, S.; Bathen, B.; Batigne, G.; Batista Camejo, A.; Batyunya, B.; Batzing, P. C.; Bearden, I. G.; Beck, H.; Bedda, C.; Behera, N. K.; Belikov, I.; Bellini, F.; Bello Martinez, H.; Bellwied, R.; Belmont, R.; Belmont-Moreno, E.; Belyaev, V.; Benacek, P.; Bencedi, G.; Beole, S.; Berceanu, I.; Bercuci, A.; Berdnikov, Y.; Berenyi, D.; Bertens, R. A.; Berzano, D.; Betev, L.; Bhasin, A.; Bhat, I. R.; Bhati, A. K.; Bhattacharjee, B.; Bhom, J.; Bianchi, L.; Bianchi, N.; Bianchin, C.; Bielčík, J.; Bielčíková, J.; Bilandzic, A.; Biro, G.; Biswas, R.; Biswas, S.; Bjelogrlic, S.; Blair, J. T.; Blau, D.; Blume, C.; Bock, F.; Bogdanov, A.; Bøggild, H.; Boldizsár, L.; Bombara, M.; Book, J.; Borel, H.; Borissov, A.; Borri, M.; Bossú, F.; Botta, E.; Bourjau, C.; Braun-Munzinger, P.; Bregant, M.; Breitner, T.; Broker, T. A.; Browning, T. A.; Broz, M.; Brucken, E. J.; Bruna, E.; Bruno, G. E.; Budnikov, D.; Buesching, H.; Bufalino, S.; Buncic, P.; Busch, O.; Buthelezi, Z.; Butt, J. B.; Buxton, J. T.; Caffarri, D.; Cai, X.; Caines, H.; Calero Diaz, L.; Caliva, A.; Calvo Villar, E.; Camerini, P.; Carena, F.; Carena, W.; Carnesecchi, F.; Castillo Castellanos, J.; Castro, A. J.; Casula, E. A. R.; Ceballos Sanchez, C.; Cerello, P.; Cerkala, J.; Chang, B.; Chapeland, S.; Chartier, M.; Charvet, J. L.; Chattopadhyay, S.; Chattopadhyay, S.; Chauvin, A.; Chelnokov, V.; Cherney, M.; Cheshkov, C.; Cheynis, B.; Chibante Barroso, V.; Chinellato, D. D.; Cho, S.; Chochula, P.; Choi, K.; Chojnacki, M.; Choudhury, S.; Christakoglou, P.; Christensen, C. H.; Christiansen, P.; Chujo, T.; Chung, S. U.; Cicalo, C.; Cifarelli, L.; Cindolo, F.; Cleymans, J.; Colamaria, F.; Colella, D.; Collu, A.; Colocci, M.; Conesa Balbastre, G.; Conesa del Valle, Z.; Connors, M. E.; Contreras, J. G.; Cormier, T. M.; Corrales Morales, Y.; Cortés Maldonado, I.; Cortese, P.; Cosentino, M. R.; Costa, F.; Crochet, P.; Cruz Albino, R.; Cuautle, E.; Cunqueiro, L.; Dahms, T.; Dainese, A.; Danu, A.; Das, D.; Das, I.; Das, S.; Dash, A.; Dash, S.; De, S.; De Caro, A.; de Cataldo, G.; de Conti, C.; de Cuveland, J.; De Falco, A.; De Gruttola, D.; De Marco, N.; De Pasquale, S.; Deisting, A.; Deloff, A.; Dénes, E.; Deplano, C.; Dhankher, P.; Di Bari, D.; Di Mauro, A.; Di Nezza, P.; Diaz Corchero, M. A.; Dietel, T.; Dillenseger, P.; Divià, R.; Djuvsland, Ø.; Dobrin, A.; Domenicis Gimenez, D.; Dönigus, B.; Dordic, O.; Drozhzhova, T.; Dubey, A. K.; Dubla, A.; Ducroux, L.; Dupieux, P.; Ehlers, R. J.; Elia, D.; Endress, E.; Engel, H.; Epple, E.; Erazmus, B.; Erdemir, I.; Erhardt, F.; Espagnon, B.; Estienne, M.; Esumi, S.; Eum, J.; Evans, D.; Evdokimov, S.; Eyyubova, G.; Fabbietti, L.; Fabris, D.; Faivre, J.; Fantoni, A.; Fasel, M.; Feldkamp, L.; Feliciello, A.; Feofilov, G.; Ferencei, J.; Fernández Téllez, A.; Ferreiro, E. G.; Ferretti, A.; Festanti, A.; Feuillard, V. J. G.; Figiel, J.; Figueredo, M. A. S.; Filchagin, S.; Finogeev, D.; Fionda, F. M.; Fiore, E. M.; Fleck, M. G.; Floris, M.; Foertsch, S.; Foka, P.; Fokin, S.; Fragiacomo, E.; Francescon, A.; Frankenfeld, U.; Fronze, G. G.; Fuchs, U.; Furget, C.; Furs, A.; Fusco Girard, M.; Gaardhøje, J. J.; Gagliardi, M.; Gago, A. M.; Gallio, M.; Gangadharan, D. R.; Ganoti, P.; Gao, C.; Garabatos, C.; Garcia-Solis, E.; Gargiulo, C.; Gasik, P.; Gauger, E. F.; Germain, M.; Gheata, A.; Gheata, M.; Ghosh, P.; Ghosh, S. K.; Gianotti, P.; Giubellino, P.; Giubilato, P.; Gladysz-Dziadus, E.; Glässel, P.; Goméz Coral, D. M.; Gomez Ramirez, A.; Gonzalez, V.; González-Zamora, P.; Gorbunov, S.; Görlich, L.; Gotovac, S.; Grabski, V.; Grachov, O. A.; Graczykowski, L. K.; Graham, K. L.; Grelli, A.; Grigoras, A.; Grigoras, C.; Grigoriev, V.; Grigoryan, A.; Grigoryan, S.; Grinyov, B.; Grion, N.; Gronefeld, J. M.; Grosse-Oetringhaus, J. F.; Grossiord, J.-Y.; Grosso, R.; Guber, F.; Guernane, R.; Guerzoni, B.; Gulbrandsen, K.; Gunji, T.; Gupta, A.; Gupta, R.; Haake, R.; Haaland, Ø.; Hadjidakis, C.; Haiduc, M.; Hamagaki, H.; Hamar, G.; Hamon, J. C.; Harris, J. W.; Harton, A.; Hatzifotiadou, D.; Hayashi, S.; Heckel, S. T.; Helstrup, H.; Herghelegiu, A.; Herrera Corral, G.; Hess, B. A.; Hetland, K. F.; Hillemanns, H.; Hippolyte, B.; Horak, D.; Hosokawa, R.; Hristov, P.; Huang, M.; Humanic, T. J.; Hussain, N.; Hussain, T.; Hutter, D.; Hwang, D. S.; Ilkaev, R.; Inaba, M.; Incani, E.; Ippolitov, M.; Irfan, M.; Ivanov, M.; Ivanov, V.; Izucheev, V.; Jacazio, N.; Jacobs, P. M.; Jadhav, M. B.; Jadlovska, S.; Jadlovsky, J.; Jahnke, C.; Jakubowska, M. J.; Jang, H. J.; Janik, M. A.; Jayarathna, P. H. S. Y.; Jena, C.; Jena, S.; Jimenez Bustamante, R. T.; Jones, P. G.; Jung, H.; Jusko, A.; Kalinak, P.; Kalweit, A.; Kamin, J.; Kang, J. H.; Kaplin, V.; Kar, S.; Karasu Uysal, A.; Karavichev, O.; Karavicheva, T.; Karayan, L.; Karpechev, E.; Kebschull, U.; Keidel, R.; Keijdener, D. L. D.; Keil, M.; Mohisin Khan, M.; Khan, P.; Khan, S. A.; Khanzadeev, A.; Kharlov, Y.; Kileng, B.; Kim, D. W.; Kim, D. J.; Kim, D.; Kim, H.; Kim, J. S.; Kim, M.; Kim, M.; Kim, S.; Kim, T.; Kirsch, S.; Kisel, I.; Kiselev, S.; Kisiel, A.; Kiss, G.; Klay, J. L.; Klein, C.; Klein, J.; Klein-Bösing, C.; Klewin, S.; Kluge, A.; Knichel, M. L.; Knospe, A. G.; Kobdaj, C.; Kofarago, M.; Kollegger, T.; Kolojvari, A.; Kondratiev, V.; Kondratyeva, N.; Kondratyuk, E.; Konevskikh, A.; Kopcik, M.; Kour, M.; Kouzinopoulos, C.; Kovalenko, O.; Kovalenko, V.; Kowalski, M.; Koyithatta Meethaleveedu, G.; Králik, I.; Kravčáková, A.; Kretz, M.; Krivda, M.; Krizek, F.; Kryshen, E.; Krzewicki, M.; Kubera, A. M.; Kučera, V.; Kuhn, C.; Kuijer, P. G.; Kumar, A.; Kumar, J.; Kumar, L.; Kumar, S.; Kurashvili, P.; Kurepin, A.; Kurepin, A. B.; Kuryakin, A.; Kweon, M. J.; Kwon, Y.; La Pointe, S. L.; La Rocca, P.; Ladron de Guevara, P.; Lagana Fernandes, C.; Lakomov, I.; Langoy, R.; Lara, C.; Lardeux, A.; Lattuca, A.; Laudi, E.; Lea, R.; Leardini, L.; Lee, G. R.; Lee, S.; Lehas, F.; Lemmon, R. C.; Lenti, V.; Leogrande, E.; León Monzón, I.; León Vargas, H.; Leoncino, M.; Lévai, P.; Li, S.; Li, X.; Lien, J.; Lietava, R.; Lindal, S.; Lindenstruth, V.; Lippmann, C.; Lisa, M. A.; Ljunggren, H. M.; Lodato, D. F.; Loenne, P. I.; Loginov, V.; Loizides, C.; Lopez, X.; López Torres, E.; Lowe, A.; Luettig, P.; Lunardon, M.; Luparello, G.; Lutz, T. H.; Maevskaya, A.; Mager, M.; Mahajan, S.; Mahmood, S. M.; Maire, A.; Majka, R. D.; Malaev, M.; Maldonado Cervantes, I.; Malinina, L.; Mal'Kevich, D.; Malzacher, P.; Mamonov, A.; Manko, V.; Manso, F.; Manzari, V.; Marchisone, M.; Mareš, J.; Margagliotti, G. V.; Margotti, A.; Margutti, J.; Marín, A.; Markert, C.; Marquard, M.; Martin, N. A.; Martin Blanco, J.; Martinengo, P.; Martínez, M. I.; Martínez García, G.; Martinez Pedreira, M.; Mas, A.; Masciocchi, S.; Masera, M.; Masoni, A.; Massacrier, L.; Mastroserio, A.; Matyja, A.; Mayer, C.; Mazer, J.; Mazzoni, M. A.; Mcdonald, D.; Meddi, F.; Melikyan, Y.; Menchaca-Rocha, A.; Meninno, E.; Mercado Pérez, J.; Meres, M.; Miake, Y.; Mieskolainen, M. M.; Mikhaylov, K.; Milano, L.; Milosevic, J.; Minervini, L. M.; Mischke, A.; Mishra, A. N.; Miskowiec, D.; Mitra, J.; Mitu, C. M.; Mohammadi, N.; Mohanty, B.; Molnar, L.; Montaño Zetina, L.; Montes, E.; Moreira De Godoy, D. A.; Moreno, L. A. P.; Moretto, S.; Morreale, A.; Morsch, A.; Muccifora, V.; Mudnic, E.; Mühlheim, D.; Muhuri, S.; Mukherjee, M.; Mulligan, J. D.; Munhoz, M. G.; Munzer, R. H.; Murakami, H.; Murray, S.; Musa, L.; Musinsky, J.; Naik, B.; Nair, R.; Nandi, B. K.; Nania, R.; Nappi, E.; Naru, M. U.; Natal da Luz, H.; Nattrass, C.; Navarro, S. R.; Nayak, K.; Nayak, R.; Nayak, T. K.; Nazarenko, S.; Nedosekin, A.; Nellen, L.; Ng, F.; Nicassio, M.; Niculescu, M.; Niedziela, J.; Nielsen, B. S.; Nikolaev, S.; Nikulin, S.; Nikulin, V.; Noferini, F.; Nomokonov, P.; Nooren, G.; Noris, J. C. C.; Norman, J.; Nyanin, A.; Nystrand, J.; Oeschler, H.; Oh, S.; Oh, S. K.; Ohlson, A.; Okatan, A.; Okubo, T.; Olah, L.; Oleniacz, J.; Oliveira Da Silva, A. C.; Oliver, M. H.; Onderwaater, J.; Oppedisano, C.; Orava, R.; Ortiz Velasquez, A.; Oskarsson, A.; Otwinowski, J.; Oyama, K.; Ozdemir, M.; Pachmayer, Y.; Pagano, P.; Paić, G.; Pal, S. K.; Pan, J.; Pandey, A. K.; Papcun, P.; Papikyan, V.; Pappalardo, G. S.; Pareek, P.; Park, W. J.; Parmar, S.; Passfeld, A.; Paticchio, V.; Patra, R. N.; Paul, B.; Pei, H.; Peitzmann, T.; Pereira Da Costa, H.; Peresunko, D.; Pérez Lara, C. E.; Perez Lezama, E.; Peskov, V.; Pestov, Y.; Petráček, V.; Petrov, V.; Petrovici, M.; Petta, C.; Piano, S.; Pikna, M.; Pillot, P.; Pimentel, L. O. D. L.; Pinazza, O.; Pinsky, L.; Piyarathna, D. B.; Ploskon, M.; Planinic, M.; Pluta, J.; Pochybova, S.; Podesta-Lerma, P. L. M.; Poghosyan, M. G.; Polichtchouk, B.; Poljak, N.; Poonsawat, W.; Pop, A.; Porteboeuf-Houssais, S.; Porter, J.; Pospisil, J.; Prasad, S. K.; Preghenella, R.; Prino, F.; Pruneau, C. A.; Pshenichnov, I.; Puccio, M.; Puddu, G.; Pujahari, P.; Punin, V.; Putschke, J.; Qvigstad, H.; Rachevski, A.; Raha, S.; Rajput, S.; Rak, J.; Rakotozafindrabe, A.; Ramello, L.; Rami, F.; Raniwala, R.; Raniwala, S.; Räsänen, S. S.; Rascanu, B. T.; Rathee, D.; Read, K. F.; Redlich, K.; Reed, R. J.; Rehman, A.; Reichelt, P.; Reidt, F.; Ren, X.; Renfordt, R.; Reolon, A. R.; Reshetin, A.; Revol, J.-P.; Reygers, K.; Riabov, V.; Ricci, R. A.; Richert, T.; Richter, M.; Riedler, P.; Riegler, W.; Riggi, F.; Ristea, C.; Rocco, E.; Rodríguez Cahuantzi, M.; Rodriguez Manso, A.; Røed, K.; Rogochaya, E.; Rohr, D.; Röhrich, D.; Romita, R.; Ronchetti, F.; Ronflette, L.; Rosnet, P.; Rossi, A.; Roukoutakis, F.; Roy, A.; Roy, C.; Roy, P.; Rubio Montero, A. J.; Rui, R.; Russo, R.; Ryabinkin, E.; Ryabov, Y.; Rybicki, A.; Sadovsky, S.; Šafařík, K.; Sahlmuller, B.; Sahoo, P.; Sahoo, R.; Sahoo, S.; Sahu, P. K.; Saini, J.; Sakai, S.; Saleh, M. A.; Salzwedel, J.; Sambyal, S.; Samsonov, V.; Šándor, L.; Sandoval, A.; Sano, M.; Sarkar, D.; Sarma, P.; Scapparone, E.; Scarlassara, F.; Schiaua, C.; Schicker, R.; Schmidt, C.; Schmidt, H. R.; Schuchmann, S.; Schukraft, J.; Schulc, M.; Schuster, T.; Schutz, Y.; Schwarz, K.; Schweda, K.; Scioli, G.; Scomparin, E.; Scott, R.; Šefčík, M.; Seger, J. E.; Sekiguchi, Y.; Sekihata, D.; Selyuzhenkov, I.; Senosi, K.; Senyukov, S.; Serradilla, E.; Sevcenco, A.; Shabanov, A.; Shabetai, A.; Shadura, O.; Shahoyan, R.; Shangaraev, A.; Sharma, A.; Sharma, M.; Sharma, M.; Sharma, N.; Shigaki, K.; Shtejer, K.; Sibiriak, Y.; Siddhanta, S.; Sielewicz, K. M.; Siemiarczuk, T.; Silvermyr, D.; Silvestre, C.; Simatovic, G.; Simonetti, G.; Singaraju, R.; Singh, R.; Singha, S.; Singhal, V.; Sinha, B. C.; Sinha, T.; Sitar, B.; Sitta, M.; Skaali, T. B.; Slupecki, M.; Smirnov, N.; Snellings, R. J. M.; Snellman, T. W.; Søgaard, C.; Song, J.; Song, M.; Song, Z.; Soramel, F.; Sorensen, S.; de Souza, R. D.; Sozzi, F.; Spacek, M.; Spiriti, E.; Sputowska, I.; Spyropoulou-Stassinaki, M.; Stachel, J.; Stan, I.; Stankus, P.; Stefanek, G.; Stenlund, E.; Steyn, G.; Stiller, J. H.; Stocco, D.; Strmen, P.; Suaide, A. A. P.; Sugitate, T.; Suire, C.; Suleymanov, M.; Suljic, M.; Sultanov, R.; Šumbera, M.; Szabo, A.; Szanto de Toledo, A.; Szarka, I.; Szczepankiewicz, A.; Szymanski, M.; Tabassam, U.; Takahashi, J.; Tambave, G. J.; Tanaka, N.; Tangaro, M. A.; Tarhini, M.; Tariq, M.; Tarzila, M. G.; Tauro, A.; Tejeda Muñoz, G.; Telesca, A.; Terasaki, K.; Terrevoli, C.; Teyssier, B.; Thäder, J.; Thomas, D.; Tieulent, R.; Timmins, A. R.; Toia, A.; Trogolo, S.; Trombetta, G.; Trubnikov, V.; Trzaska, W. H.; Tsuji, T.; Tumkin, A.; Turrisi, R.; Tveter, T. S.; Ullaland, K.; Uras, A.; Usai, G. L.; Utrobicic, A.; Vajzer, M.; Vala, M.; Valencia Palomo, L.; Vallero, S.; Van Der Maarel, J.; Van Hoorne, J. W.; van Leeuwen, M.; Vanat, T.; Vande Vyvre, P.; Varga, D.; Vargas, A.; Vargyas, M.; Varma, R.; Vasileiou, M.; Vasiliev, A.; Vauthier, A.; Vechernin, V.; Veen, A. M.; Veldhoen, M.; Velure, A.; Venaruzzo, M.; Vercellin, E.; Vergara Limón, S.; Vernet, R.; Verweij, M.; Vickovic, L.; Viesti, G.; Viinikainen, J.; Vilakazi, Z.; Villalobos Baillie, O.; Villatoro Tello, A.; Vinogradov, A.; Vinogradov, L.; Vinogradov, Y.; Virgili, T.; Vislavicius, V.; Viyogi, Y. P.; Vodopyanov, A.; Völkl, M. A.; Voloshin, K.; Voloshin, S. A.; Volpe, G.; von Haller, B.; Vorobyev, I.; Vranic, D.; Vrláková, J.; Vulpescu, B.; Wagner, B.; Wagner, J.; Wang, H.; Wang, M.; Watanabe, D.; Watanabe, Y.; Weber, M.; Weber, S. G.; Weiser, D. F.; Wessels, J. P.; Westerhoff, U.; Whitehead, A. M.; Wiechula, J.; Wikne, J.; Wilde, M.; Wilk, G.; Wilkinson, J.; Williams, M. C. S.; Windelband, B.; Winn, M.; Yaldo, C. G.; Yang, H.; Yang, P.; Yano, S.; Yasar, C.; Yin, Z.; Yokoyama, H.; Yoo, I.-K.; Yoon, J. H.; Yurchenko, V.; Yushmanov, I.; Zaborowska, A.; Zaccolo, V.; Zaman, A.; Zampolli, C.; Zanoli, H. J. C.; Zaporozhets, S.; Zardoshti, N.; Zarochentsev, A.; Závada, P.; Zaviyalov, N.; Zbroszczyk, H.; Zgura, I. S.; Zhalov, M.; Zhang, H.; Zhang, X.; Zhang, Y.; Zhang, C.; Zhang, Z.; Zhao, C.; Zhigareva, N.; Zhou, D.; Zhou, Y.; Zhou, Z.; Zhu, H.; Zhu, J.; Zichichi, A.; Zimmermann, A.; Zimmermann, M. B.; Zinovjev, G.; Zyzak, M.

2016-08-01

The measurement of prompt D-meson production as a function of multiplicity in p-Pb collisions at √{s_{NN}}=5.02 TeV with the ALICE detector at the LHC is reported. D0, D+ and D∗+ mesons are reconstructed via their hadronic decay channels in the centre-of-mass rapidity range -0 .96 < y cms < 0 .04 and transverse momentum interval 1

Sustainable land cover and terrain modification to enhance convection and precipitation in the arid region of the United Arab Emirates

NASA Astrophysics Data System (ADS)

Wulfmeyer, V.; Branch, O.; Adebabseh, A.; Temimi, M.

2017-12-01

Irrigated plantations and modified terrain can provide a sustainable means of enhancing convective rainfall in arid regions like the United Arab Emirates, or UAE, and can be used to aid ongoing cloud seeding operations through the geographic-localization of seedable cloud formation. The first method, the planting of vast irrigated plantations of hardy desert shrubs, can lead to wind convergence and vertical mixing through increased roughness and modified radiative balances. When upper-air atmospheric instability is present, these phenomena can initiate convection. The second method, increasing the elevation of moderate-sized mountains, is based on the correlation between elevation and the number of summertime convection initiation events observed in the mountains of the UAE and Oman. This augmentation of existing orographic features should therefore increase the likelihood and geographic range of convection initiation events. High-resolution simulations provide a powerful means of assessing the likely impacts of land surface modifications. Previous convection-permitting simulations have yielded some evidential support for these hypotheses, but higher resolutions down to 1 km provide more detail regarding convective processes and land surface representation. Using seasonal simulations with the WRF-NOAHMP land-atmosphere model at a 2.5 km resolution, we identify frequent zones of convergence and atmospheric instability in the UAE and select interesting cases. Using these results, as well as an agricultural feasibility study, we identify optimal plantation positions within the UAE. We then run realistic plantation scenarios for single case studies at 1 km resolution. Using the same cases, we simulate the impact of augmenting mountain elevations on convective processes, with the augmentation being achieved through GIS-based modification of the terrain data. For both methods, we assess the impacts quantitatively and qualitatively, and assess key processes and dependencies. If we can demonstrate that convective rainfall would be enhanced through feasible agricultural and engineering methods, then land surface-based weather modification deserves serious consideration as a solution for water scarcity and anthropogenic climate change.

Simply Imagining Sunshine, Lollipops and Rainbows Will Not Budge the Bias: The Role of Ambiguity in Interpretive Bias Modification.

PubMed

Clarke, Patrick J F; Nanthakumar, Shenooka; Notebaert, Lies; Holmes, Emily A; Blackwell, Simon E; Macleod, Colin

2014-01-01

Imagery-based interpretive bias modification (CBM-I) involves repeatedly imagining scenarios that are initially ambiguous before being resolved as either positive or negative in the last word/s. While the presence of such ambiguity is assumed to be important to achieve change in selective interpretation, it is also possible that the act of repeatedly imagining positive or negative events could produce such change in the absence of ambiguity. The present study sought to examine whether the ambiguity in imagery-based CBM-I is necessary to elicit change in interpretive bias, or, if the emotional content of the imagined scenarios is sufficient to produce such change. An imagery-based CBM-I task was delivered to participants in one of four conditions, where the valence of imagined scenarios were either positive or negative, and the ambiguity of the scenario was either present (until the last word/s) or the ambiguity was absent (emotional valence was evident from the start). Results indicate that only those who received scenarios in which the ambiguity was present acquired an interpretive bias consistent with the emotional valence of the scenarios, suggesting that the act of imagining positive or negative events will only influence patterns of interpretation when the emotional ambiguity is a consistent feature.

Event-based Sensing for Space Situational Awareness

NASA Astrophysics Data System (ADS)

Cohen, G.; Afshar, S.; van Schaik, A.; Wabnitz, A.; Bessell, T.; Rutten, M.; Morreale, B.

A revolutionary type of imaging device, known as a silicon retina or event-based sensor, has recently been developed and is gaining in popularity in the field of artificial vision systems. These devices are inspired by a biological retina and operate in a significantly different way to traditional CCD-based imaging sensors. While a CCD produces frames of pixel intensities, an event-based sensor produces a continuous stream of events, each of which is generated when a pixel detects a change in log light intensity. These pixels operate asynchronously and independently, producing an event-based output with high temporal resolution. There are also no fixed exposure times, allowing these devices to offer a very high dynamic range independently for each pixel. Additionally, these devices offer high-speed, low power operation and a sparse spatiotemporal output. As a consequence, the data from these sensors must be interpreted in a significantly different way to traditional imaging sensors and this paper explores the advantages this technology provides for space imaging. The applicability and capabilities of event-based sensors for SSA applications are demonstrated through telescope field trials. Trial results have confirmed that the devices are capable of observing resident space objects from LEO through to GEO orbital regimes. Significantly, observations of RSOs were made during both day-time and nighttime (terminator) conditions without modification to the camera or optics. The event based sensor’s ability to image stars and satellites during day-time hours offers a dramatic capability increase for terrestrial optical sensors. This paper shows the field testing and validation of two different architectures of event-based imaging sensors. An eventbased sensor’s asynchronous output has an intrinsically low data-rate. In addition to low-bandwidth communications requirements, the low weight, low-power and high-speed make them ideally suitable to meeting the demanding challenges required by space-based SSA systems. Results from these experiments and the systems developed highlight the applicability of event-based sensors to ground and space-based SSA tasks.

Effects of Harbor Modification on Crescent City, California's Tsunami Vulnerability

NASA Astrophysics Data System (ADS)

Dengler, Lori; Uslu, Burak

2011-06-01

More damaging tsunamis have impacted Crescent City, California in historic times than any other location on the West Coast of the USA. Crescent City's harbor has undergone significant modification since the early 20th century, including construction of several breakwaters, dredging, and a 200 × 300 m2 small boat basin. In 2006, a M w 8.3 earthquake in the Kuril Islands generated a moderate Pacific-wide tsunami. Crescent City recorded the highest amplitudes of any tide gauge in the Pacific and was the only location to experience structural damage. Strong currents damaged docks and boats within the small boat basin, causing more than US 20 million in damage and replacement costs. We examine how modifications to Crescent City's harbor may have affected its vulnerability to moderate tsunamis such as the 2006 event. A bathymetric grid of the basin was constructed based on US Army Corps of Engineers soundings in 1964 and 1965 before the construction of the small boat basin. The method of splitting tsunamis was used to estimate tsunami water heights and current velocities at several locations in the harbor using both the 1964-1965 grid and the 2006 bathymetric grid for the 2006 Kuril event and a similar-sized source along the Sanriku coast of Japan. Model velocity outputs are compared for the two different bathymetries at the tide gauge location and at six additional computational sites in the harbor. The largest difference between the two grids is at the small boat basin entrance, where the 2006 bathymetry produces currents over three times the strength of the currents produced by the 1965 bathymetry. Peak currents from a Sanriku event are comparable to those produced by the 2006 event, and within the boat basin may have been higher. The modifications of the harbor, and in particular the addition of the small boat basin, appear to have contributed to the high current velocities and resulting damage in 2006 and help to explain why the 1933 M w 8.4-8.7 Sanriku tsunami caused no damage at Crescent City.

BM@N and MPD experiments at NICA

NASA Astrophysics Data System (ADS)

Kekelidze, Vladimir; Kolesnikov, Vadim; Sorin, Alexander

2018-02-01

The project NICA (Nuclotron-based Ion Collider fAcility) aims to study hot and baryon rich QCD matter in heavy ion collisions in the energy range = 4 - 11 GeV. The rich heavy-ion physics program will be performed at two experiments, BM@N (Baryonic Matter at Nuclotron) at beams extracted from the Nuclotron, and at MPD (Multi-Purpose Detector) at the NICA collider. This program covers a variety of phenomena in strongly interacting matter of the highest baryonic density, which includes study of collective effects, production of hyperon and hypernuclei, in-medium modification of meson properties, and event-by-event fluctuations.

Early/fast VLF events produced by the quiescent heating of the lower ionosphere by thunderstorms

NASA Astrophysics Data System (ADS)

Kabirzadeh, R.; Marshall, R. A.; Inan, U. S.

2017-06-01

Large and easily distinguishable perturbations of the VLF transmitter signals due to interactions with thundercloud-driven ionospheric modifications have been observed and studied for about three decades. These events are called "early/fast VLF" or "early VLF" events due to their immediate detection (˜20 ms) after the causative lightning flash on the ground and the fast rise time of the perturbed signal. Despite many years of study, the physical mechanisms responsible for these perturbations are still under investigation. Modifications of the sustained heating level of the ionosphere due to a lightning flash has been previously proposed as the causative mechanism of early/fast VLF events. The perturbations predicted by this mechanism, however, have been much smaller than experimental observations of 0.2-1 dB or higher. In this study, by using an improved 3-D thundercloud electrostatic upward coupling model which uses a realistic geomagnetic field, we find that the sustained heating model can predict perturbations that are consistent with reported experimental observations. Modifications in the quiescent heating of the lower ionosphere by thundercloud fields by individual lightning flashes may thus account for some observations of early/fast VLF events.

Nitric oxide-based protein modification: formation and site-specificity of protein S-nitrosylation

PubMed Central

Kovacs, Izabella; Lindermayr, Christian

2013-01-01

Nitric oxide (NO) is a reactive free radical with pleiotropic functions that participates in diverse biological processes in plants, such as germination, root development, stomatal closing, abiotic stress, and defense responses. It acts mainly through redox-based modification of cysteine residue(s) of target proteins, called protein S-nitrosylation.In this way NO regulates numerous cellular functions and signaling events in plants. Identification of S-nitrosylated substrates and their exact target cysteine residue(s) is very important to reveal the molecular mechanisms and regulatory roles of S-nitrosylation. In addition to the necessity of protein–protein interaction for trans-nitrosylation and denitrosylation reactions, the cellular redox environment and cysteine thiol micro-environment have been proposed important factors for the specificity of protein S-nitrosylation. Several methods have recently been developed for the proteomic identification of target proteins. However, the specificity of NO-based cysteine modification is still less defined. In this review, we discuss formation and specificity of S-nitrosylation. Special focus will be on potential S-nitrosylation motifs, site-specific proteomic analyses, computational predictions using different algorithms, and on structural analysis of cysteine S-nitrosylation. PMID:23717319

Functional network in posttranslational modifications: Glyco-Net in Glycoconjugate Data Bank.

PubMed

Miura, Nobuaki; Okada, Takuya; Murayama, Daisuke; Hirose, Kazuko; Sato, Taku; Hashimoto, Ryo; Fukushima, Nobuhiro

2015-01-01

Elucidating pathways related to posttranslational modifications (PTMs) such as glycosylation is of growing importance in post-genome science and technology. Graphical networks describing the relationships among glycan-related molecules, including genes, proteins, lipids, and various biological events, are considered extremely valuable and convenient tools for the systematic investigation of PTMs. Glyco-Net (http://bibi.sci.hokudai.ac.jp/functions/) can dynamically make network figures among various biological molecules and biological events. A certain molecule or event is expressed with a node, and the relationship between the molecule and the event is indicated by arrows in the network figures. In this chapter, we mention the features and current status of the Glyco-Net and a simple example of the search with the Glyco-Net.

7 CFR 987.35 - Modifications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (Marketing Agreements... RIVERSIDE COUNTY, CALIFORNIA Order Regulating Handling Marketing Policy § 987.35 Modifications. In the event the Committee subsequently determines that the marketing policy should be modified due to changing...

Mitigating Climate Change with Earth Orbital Sunshades

NASA Technical Reports Server (NTRS)

Coverstone, Victoria; Johnson, Les

2015-01-01

An array of rotating sunshades based on emerging solar sail technology will be deployed in a novel Earth orbit to provide near-continuous partial shading of the Earth, reducing the heat input to the atmosphere by blocking a small percentage of the incoming sunlight, and mitigating local weather effects of anticipated climate change over the next century. The technology will provide local cooling relief during extreme heat events (and heating relief during extreme cold events) thereby saving human lives, agriculture, livestock, water and energy needs. A synthesis of the solar sail design, the sails' operational modes, and the selected orbit combine to provide local weather modification.

Adaptable, high recall, event extraction system with minimal configuration.

PubMed

Miwa, Makoto; Ananiadou, Sophia

2015-01-01

Biomedical event extraction has been a major focus of biomedical natural language processing (BioNLP) research since the first BioNLP shared task was held in 2009. Accordingly, a large number of event extraction systems have been developed. Most such systems, however, have been developed for specific tasks and/or incorporated task specific settings, making their application to new corpora and tasks problematic without modification of the systems themselves. There is thus a need for event extraction systems that can achieve high levels of accuracy when applied to corpora in new domains, without the need for exhaustive tuning or modification, whilst retaining competitive levels of performance. We have enhanced our state-of-the-art event extraction system, EventMine, to alleviate the need for task-specific tuning. Task-specific details are specified in a configuration file, while extensive task-specific parameter tuning is avoided through the integration of a weighting method, a covariate shift method, and their combination. The task-specific configuration and weighting method have been employed within the context of two different sub-tasks of BioNLP shared task 2013, i.e. Cancer Genetics (CG) and Pathway Curation (PC), removing the need to modify the system specifically for each task. With minimal task specific configuration and tuning, EventMine achieved the 1st place in the PC task, and 2nd in the CG, achieving the highest recall for both tasks. The system has been further enhanced following the shared task by incorporating the covariate shift method and entity generalisations based on the task definitions, leading to further performance improvements. We have shown that it is possible to apply a state-of-the-art event extraction system to new tasks with high levels of performance, without having to modify the system internally. Both covariate shift and weighting methods are useful in facilitating the production of high recall systems. These methods and their combination can adapt a model to the target data with no deep tuning and little manual configuration.

Developing interpretation bias modification as a "cognitive vaccine" for depressed mood: imagining positive events makes you feel better than thinking about them verbally.

PubMed

Holmes, Emily A; Lang, Tamara J; Shah, Dhruvi M

2009-02-01

Two interpretation bias modification experiments found that mental imagery vs. verbal processing of positive material have differential emotional effects. In Experiment 1, participants were instructed to imagine positively resolved auditory descriptions or to listen to the same events while thinking about their verbal meaning. Increases in positive mood and bias were greater in the imagery than in the verbal condition, replicating E. A. Holmes, A. Mathews, T. Dalgleish, and B. Mackintosh (2006). An emotional vulnerability test showed that imagery (relative to the verbal condition) protected against a later negative mood induction. Experiment 2 created 2 new verbal conditions aimed to increase or reduce verbal comparisons. Results suggest making unfavorable comparisons with the highly positive material might be partially responsible for the inferiority of the verbal condition in Experiment 1. The findings demonstrate that imagery can play a key role in cognitive bias modification procedures and thus that task instructions are crucial. Imagining a positive event can make you feel better than thinking about the same event verbally. The authors propose that recruiting imagery will be useful in therapeutic innovations to develop a "cognitive vaccine" for depressed mood.

On the bad metallicity and phase diagrams of Fe1+δX (X =Te, Se, S, solid solutions): an electrical resistivity study

NASA Astrophysics Data System (ADS)

El Massalami, M.; Deguchi, K.; Machida, T.; Takeya, H.; Takano, Y.

2014-12-01

Based on a systematic analysis of the thermal evolution of the resistivities of Fe-based chalcogenides Fe1+δTe1-xXx (X = Se, S), it is inferred that their often observed nonmetallic resistivities are related to a presence of two resistive channels: one is a high- temperature thermally-activated process while the other is a low-temperature log-in-T process. On lowering temperature, there are often two metal-to-nonmetall crossover events: one from the high-T thermally-activated nonmetallic regime into a metal-like phase and the other from the log-in-T regime into a second metal-like phase. Based on these events, together with the magnetic and superconducting transitions, a phase diagram is constructed for each series. We discuss the origin of both processes as well as the associated crossover events. We also discuss how these resistive processes are being influenced by pressure, intercalation, disorder, doping, or sample condition and, in turn, how these modifications are shaping the associated phase diagrams.

Lipid modification of proteins in Archaea: attachment of a mevalonic acid-based lipid moiety to the surface-layer glycoprotein of Haloferax volcanii follows protein translocation.

PubMed Central

Konrad, Zvia; Eichler, Jerry

2002-01-01

Once the newly synthesized surface (S)-layer glycoprotein of the halophilic archaeaon Haloferax volcanii has traversed the plasma membrane, the protein undergoes a membrane-related, Mg(2+)-dependent maturation event, revealed as an increase in the apparent molecular mass and hydrophobicity of the protein. To test whether lipid modification of the S-layer glycoprotein could explain these observations, H. volcanii cells were incubated with a radiolabelled precursor of isoprene, [(3)H]mevalonic acid. In Archaea, isoprenoids serve as the major hydrophobic component of archaeal membrane lipids and have been shown to modify other haloarchaeal S-layer glycoproteins, although little is known of the mechanism, site or purpose of such modification. In the present study we report that the H. volcanii S-layer glycoprotein is modified by a derivative of mevalonic acid and that maturation of the protein was prevented upon treatment with mevinolin (lovastatin), an inhibitor of mevalonic acid biosynthesis. These findings suggest that lipid modification of S-layer glycoproteins is a general property of halophilic archaea and, like S-layer glycoprotein glycosylation, lipid-modification of the S-layer glycoproteins takes place on the external cell surface, i.e. following protein translocation across the membrane. PMID:12069685

Beyond histones - the expanding roles of protein lysine methylation.

PubMed

Wu, Zhouran; Connolly, Justin; Biggar, Kyle K

2017-09-01

A robust signaling network is essential for cell survival. At the molecular level, this is often mediated by as many as 200 different types of post-translational modifications (PTMs) that are made to proteins. These include well-documented examples such as phosphorylation, ubiquitination, acetylation and methylation. Of these modifications, non-histone protein lysine methylation has only recently emerged as a prevalent modification occurring on numerous proteins, thus extending its role well beyond the histone code. To date, this modification has been found to regulate protein activity, protein-protein interactions and interplay with other PTMs. As a result, lysine methylation is now known to be a coordinator of protein function and is a key driver in several cellular signaling events. Recent advances in mass spectrometry have also allowed the characterization of a growing number of lysine methylation events on an increasing number of proteins. As a result, we are now beginning to recognize lysine methylation as a dynamic event that is involved in a number of biological processes, including DNA damage repair, cell growth, metabolism and signal transduction among others. In light of current research advances, the stage is now set to study the extent of lysine methylation that exists within the entire proteome, its dynamics, and its association with physiological and pathological processes. © 2017 Federation of European Biochemical Societies.

Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

PubMed

Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; van den Hoff, Joerg

2004-11-01

Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

[Tattoos and piercings: motives for body modification in women suffering from borderline symptomatology].

PubMed

Höhner, Gesche; Teismann, Tobias; Willutzki, Ulrike

2014-02-01

Do women suffering from borderline symptomatology differ from women without these symptoms regarding their motives for body modifications?A sample of 289 women with body modifications were questioned about their tattoos, piercings and motives for body modifications as well as about symptoms of borderline personality disorder. Women with borderline symptomatology were compared to women without borderline symptomatology concerning the extent of and motives for body modification.The 2 groups showed no differences in regard to amount and extent of body modifications. The "borderline"-group considered individuality, coping and management of negative life-events to be more crucial reasons for body modification than the non-borderline females.The degree of a person's body modification is not a feasible indicator for psychopathological strain. Though, for people with borderline tendency body modification may serve as a coping strategy similar to self-injury. © Georg Thieme Verlag KG Stuttgart · New York.

Image Reconstruction for a Partially Collimated Whole Body PET Scanner

PubMed Central

Alessio, Adam M.; Schmitz, Ruth E.; MacDonald, Lawrence R.; Wollenweber, Scott D.; Stearns, Charles W.; Ross, Steven G.; Ganin, Alex; Lewellen, Thomas K.; Kinahan, Paul E.

2008-01-01

Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary. PMID:19096731

Image Reconstruction for a Partially Collimated Whole Body PET Scanner.

PubMed

Alessio, Adam M; Schmitz, Ruth E; Macdonald, Lawrence R; Wollenweber, Scott D; Stearns, Charles W; Ross, Steven G; Ganin, Alex; Lewellen, Thomas K; Kinahan, Paul E

2008-06-01

Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary.

Large developing receptive fields using a distributed and locally reprogrammable address-event receiver.

PubMed

Bamford, Simeon A; Murray, Alan F; Willshaw, David J

2010-02-01

A distributed and locally reprogrammable address-event receiver has been designed, in which incoming address-events are monitored simultaneously by all synapses, allowing for arbitrarily large axonal fan-out without reducing channel capacity. Synapses can change the address of their presynaptic neuron, allowing the distributed implementation of a biologically realistic learning rule, with both synapse formation and elimination (synaptic rewiring). Probabilistic synapse formation leads to topographic map development, made possible by a cross-chip current-mode calculation of Euclidean distance. As well as synaptic plasticity in rewiring, synapses change weights using a competitive Hebbian learning rule (spike-timing-dependent plasticity). The weight plasticity allows receptive fields to be modified based on spatio-temporal correlations in the inputs, and the rewiring plasticity allows these modifications to become embedded in the network topology.

HAARP-based Investigations of Lightning-induced Nonlinearities within the D-Region Ionosphere

NASA Astrophysics Data System (ADS)

Moore, R. C.

2015-12-01

It is well-documented that energetic lightning can produce fantastical events with the lower ionosphere. Although the High-frequency Active Auroral Research Program (HAARP) transmitter is not as powerful as lightning, it can be used to investigate the nonlinear interactions that occur within the lower ionosphere, many of which also occur during lightning-induced ionospheric events. This paper presents the best experimental results obtained during D-region modification experiments performed by the University of Florida at the HAARP observatory between 2007 and 2014, including ELF/VLF wave generation experiments, wave-wave mixing experiments, and cross-modulation experiments. We emphasize the physical processes important for lightning-ionosphere interactions that can be directly investigated using HAARP.

Common ground: small RNA programming and chromatin modifications.

PubMed

Lejeune, Erwan; Allshire, Robin C

2011-06-01

Epigenetic mechanisms regulate genome structure and expression profiles in eukaryotes. RNA interference (RNAi) and other small RNA-based chromatin-modifying activities can act to reset the epigenetic landscape at defined chromatin domains. Centromeric heterochromatin assembly is a RNAi-dependent process in the fission yeast Schizosaccharomyces pombe, and provides a paradigm for detailed examination of such epigenetic processes. Here we review recent progress in understanding the mechanisms that underpin RNAi-mediated heterochromatin formation in S. pombe. We discuss recent analyses of the events that trigger RNAi and manipulations which uncouple RNAi and chromatin modification. Finally we provide an overview of similar molecular machineries across species where related small RNA pathways appear to drive the epigenetic reprogramming in germ cells and/or during early development in metazoans. Copyright © 2011 Elsevier Ltd. All rights reserved.

Minimization of Hypoglycemia as an Adverse Event During Insulin Infusion: Further Refinement of the Yale Protocol.

PubMed

Marvin, Michael R; Inzucchi, Silvio E; Besterman, Brian J

2016-08-01

The management of hyperglycemia in the intensive care unit has been a controversial topic for more than a decade, with target ranges varying from 80-110 mg/dL to <200 mg/dL. Multiple insulin infusion protocols exist, including several computerized protocols, which have attempted to achieve these targets. Importantly, compliance with these protocols has not been a focus of clinical studies. GlucoCare™, a Food and Drug Administration (FDA)-cleared insulin-dosing calculator, was originally designed based on the Yale Insulin Infusion Protocol to target 100-140 mg/dL and has undergone several modifications to reduce hypoglycemia. The original Yale protocol was modified from 100-140 mg/dL to a range of 120-140 mg/dL (GlucoCare 120-140) and then to 140 mg/dL (GlucoCare 140, not a range but a single blood glucose [BG] level target) in an iterative and evidence-based manner to eliminate hypoglycemia <70 mg/dL. The final modification [GlucoCare 140(B)] includes the addition of bolus insulin "midprotocol" during an insulin infusion to reduce peak insulin rates for insulin-resistant patients. This study examined the results of these protocol modifications and evaluated the role of compliance with the protocol in the incidence of hypoglycemia <70 mg/dL. Protocol modifications resulted in mean BG levels of 133.4, 136.4, 143.8, and 146.4 mg/dL and hypoglycemic BG readings <70 mg/dL of 0.998%, 0.367%, 0.256%, and 0.04% for the 100-140, 120-140, 140, and 140(B) protocols, respectively (P < 0.001). Adherence to the glucose check interval significantly reduced the incidence of hypoglycemia (P < 0.001). Protocol modifications led to a reduction in peak insulin infusion rates (P < 0.001) and the need for dextrose-containing boluses (P < 0.001). This study demonstrates that refinements in protocol design can improve glucose control in critically ill patients and that the use of GlucoCare 140(B) can eliminate all significant hypoglycemia while achieving mean glucose levels between 140 and 150 mg/dL. In addition, attention to the timely performance of glucose levels can also reduce hypoglycemic events.

Mediational Modification of Creative Behaviors.

ERIC Educational Resources Information Center

Russell, Crawford L.

1981-01-01

Adapting the cognitive behavior modification work of Bandura and Mahoney, the author suggests a "mediational approach" to teaching creativity in the art classroom; here the desired behavior is modeled, guided experience is offered for practice, then reward in the form of approval is given for successful completion of the event. (Editor/SJL)

Experimental annotation of post-translational features and translated coding regions in the pathogen Salmonella Typhimurium

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

Ansong, Charles; Tolic, Nikola; Purvine, Samuel O.

Complete and accurate genome annotation is crucial for comprehensive and systematic studies of biological systems. For example systems biology-oriented genome scale modeling efforts greatly benefit from accurate annotation of protein-coding genes to develop proper functioning models. However, determining protein-coding genes for most new genomes is almost completely performed by inference, using computational predictions with significant documented error rates (> 15%). Furthermore, gene prediction programs provide no information on biologically important post-translational processing events critical for protein function. With the ability to directly measure peptides arising from expressed proteins, mass spectrometry-based proteomics approaches can be used to augment and verify codingmore » regions of a genomic sequence and importantly detect post-translational processing events. In this study we utilized “shotgun” proteomics to guide accurate primary genome annotation of the bacterial pathogen Salmonella Typhimurium 14028 to facilitate a systems-level understanding of Salmonella biology. The data provides protein-level experimental confirmation for 44% of predicted protein-coding genes, suggests revisions to 48 genes assigned incorrect translational start sites, and uncovers 13 non-annotated genes missed by gene prediction programs. We also present a comprehensive analysis of post-translational processing events in Salmonella, revealing a wide range of complex chemical modifications (70 distinct modifications) and confirming more than 130 signal peptide and N-terminal methionine cleavage events in Salmonella. This study highlights several ways in which proteomics data applied during the primary stages of annotation can improve the quality of genome annotations, especially with regards to the annotation of mature protein products.« less

Intrapartum electrocardiogram alteration in fetuses with congenital heart disease: a case-control study.

PubMed

Gay, Estelle; Bornallet, Géraldine; Gaucherand, Pascal; Doret, Muriel

2015-11-01

To assess if the fetal electrocardiogram especially ST segment is modified by congenital heart diseases: modifications in frequencies of the different ST events and modifications in signal quality. A retrospective case-control study, comparing frequencies of the different ST events and the quality of the signal between fetuses with congenital heart diseases and fetuses without congenital heart disease. From 2000 to 2011, fifty-eight fetuses with congenital heart disease had their heart rate recording using a STAN device during labor. Control group was fetuses who were born just before a case and had a STAN as a second line for intrapartum surveillance. Cases and controls were matched on parity, gestational age at birth, presence of growth restriction and umbilical artery pH. Frequencies of the different ST event and quality of the signal were first analyzed for the global labor recording, and then separately for the first and the second phase of labor. No statistically significant difference in ST event frequencies between fetuses with congenital heart disease and the control group was found. Regarding the quality of the signal, 11.49% (±18.82) of recording time is a signal loss for fetus with congenital heart disease whereas only 5.18% (±10.67) for the control group (p=0.028). This is the first study investigating for intrapartum electrocardiogram modification in fetus with congenital heart disease. Congenital heart diseases do not modify frequencies of ST events. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Feasibility of interdisciplinary community-based fall risk screening.

PubMed

Elliott, Sharon J; Ivanescu, Andrada; Leland, Natalie E; Fogo, Jennifer; Painter, Jane A; Trujillo, Leonard G

2012-01-01

This pilot study examined the feasibility of (1) conducting interdisciplinary fall risk screens at a communitywide adult fall prevention event and (2) collecting preliminary follow-up data from people screened at the event about balance confidence and home and activity modifications made after receiving educational information at the event. We conducted a pilot study with pre- and posttesting (4-mo follow-up) with 35 community-dwelling adults ≥55 yr old. Approximately half the participants were at risk for falls. Most participants who anticipated making environmental or activity changes to reduce fall risk initiated changes (n = 8/11; 72.7%) during the 4-mo follow-up period. We found no significant difference in participants' balance confidence between baseline (median = 62.81) and follow-up (median = 64.06) as measured by the Activities-specific Balance Confidence scale. Conducting interdisciplinary fall risk screens at an adult fall prevention event is feasible and can facilitate environmental and behavior changes to reduce fall risk. Copyright © 2012 by the American Occupational Therapy Association, Inc.

Microcontroller based resonance tracking unit for time resolved continuous wave cavity-ringdown spectroscopy measurements.

PubMed

Votava, Ondrej; Mašát, Milan; Parker, Alexander E; Jain, Chaithania; Fittschen, Christa

2012-04-01

We present in this work a new tracking servoloop electronics for continuous wave cavity-ringdown absorption spectroscopy (cw-CRDS) and its application to time resolved cw-CRDS measurements by coupling the system with a pulsed laser photolysis set-up. The tracking unit significantly increases the repetition rate of the CRDS events and thus improves effective time resolution (and/or the signal-to-noise ratio) in kinetics studies with cw-CRDS in given data acquisition time. The tracking servoloop uses novel strategy to track the cavity resonances that result in a fast relocking (few ms) after the loss of tracking due to an external disturbance. The microcontroller based design is highly flexible and thus advanced tracking strategies are easy to implement by the firmware modification without the need to modify the hardware. We believe that the performance of many existing cw-CRDS experiments, not only time-resolved, can be improved with such tracking unit without any additional modification to the experiment. © 2012 American Institute of Physics

Nurse practitioner-based sign-out system to facilitate patient communication on a neurosurgical service: a pilot study with recommendations.

PubMed

Rabinovitch, Deborah L; Hamill, Melinda; Zanchetta, Clauda; Bernstein, Mark

2009-12-01

Failure to communicate important patient information between physicians causes medical errors and adverse patient events. On-call neurosurgery physicians at the Toronto Western Hospital do not know the medical details of all the patients that they are covering at night because they do not care for the entire service of patients during the day. Because there is no formal handover system to transfer patient information to the on-call physician, a nurse practitioner-based sign-out system was recently introduced. Its effectiveness for communication was evaluated with preintervention-postintervention questionnaires and by recording daily logins. There was a statistically significant decrease in number of logins after 8 weeks of use (p = .05, Fisher's exact test), and the tool was abandoned after 16 weeks. Modifications identified to improve the system include the ability to sort by attending physician and to automatically populate the list with new patients. Effective communication is important for reducing medical errors, and perhaps these modifications will facilitate this important endeavor.

Event- and Time-Driven Techniques Using Parallel CPU-GPU Co-processing for Spiking Neural Networks

PubMed Central

Naveros, Francisco; Garrido, Jesus A.; Carrillo, Richard R.; Ros, Eduardo; Luque, Niceto R.

2017-01-01

Modeling and simulating the neural structures which make up our central neural system is instrumental for deciphering the computational neural cues beneath. Higher levels of biological plausibility usually impose higher levels of complexity in mathematical modeling, from neural to behavioral levels. This paper focuses on overcoming the simulation problems (accuracy and performance) derived from using higher levels of mathematical complexity at a neural level. This study proposes different techniques for simulating neural models that hold incremental levels of mathematical complexity: leaky integrate-and-fire (LIF), adaptive exponential integrate-and-fire (AdEx), and Hodgkin-Huxley (HH) neural models (ranged from low to high neural complexity). The studied techniques are classified into two main families depending on how the neural-model dynamic evaluation is computed: the event-driven or the time-driven families. Whilst event-driven techniques pre-compile and store the neural dynamics within look-up tables, time-driven techniques compute the neural dynamics iteratively during the simulation time. We propose two modifications for the event-driven family: a look-up table recombination to better cope with the incremental neural complexity together with a better handling of the synchronous input activity. Regarding the time-driven family, we propose a modification in computing the neural dynamics: the bi-fixed-step integration method. This method automatically adjusts the simulation step size to better cope with the stiffness of the neural model dynamics running in CPU platforms. One version of this method is also implemented for hybrid CPU-GPU platforms. Finally, we analyze how the performance and accuracy of these modifications evolve with increasing levels of neural complexity. We also demonstrate how the proposed modifications which constitute the main contribution of this study systematically outperform the traditional event- and time-driven techniques under increasing levels of neural complexity. PMID:28223930

Adaptable, high recall, event extraction system with minimal configuration

PubMed Central

2015-01-01

Background Biomedical event extraction has been a major focus of biomedical natural language processing (BioNLP) research since the first BioNLP shared task was held in 2009. Accordingly, a large number of event extraction systems have been developed. Most such systems, however, have been developed for specific tasks and/or incorporated task specific settings, making their application to new corpora and tasks problematic without modification of the systems themselves. There is thus a need for event extraction systems that can achieve high levels of accuracy when applied to corpora in new domains, without the need for exhaustive tuning or modification, whilst retaining competitive levels of performance. Results We have enhanced our state-of-the-art event extraction system, EventMine, to alleviate the need for task-specific tuning. Task-specific details are specified in a configuration file, while extensive task-specific parameter tuning is avoided through the integration of a weighting method, a covariate shift method, and their combination. The task-specific configuration and weighting method have been employed within the context of two different sub-tasks of BioNLP shared task 2013, i.e. Cancer Genetics (CG) and Pathway Curation (PC), removing the need to modify the system specifically for each task. With minimal task specific configuration and tuning, EventMine achieved the 1st place in the PC task, and 2nd in the CG, achieving the highest recall for both tasks. The system has been further enhanced following the shared task by incorporating the covariate shift method and entity generalisations based on the task definitions, leading to further performance improvements. Conclusions We have shown that it is possible to apply a state-of-the-art event extraction system to new tasks with high levels of performance, without having to modify the system internally. Both covariate shift and weighting methods are useful in facilitating the production of high recall systems. These methods and their combination can adapt a model to the target data with no deep tuning and little manual configuration. PMID:26201408

Biochemical and Structural Studies of RNA Modification and Repair

ERIC Educational Resources Information Center

Chan, Chio Mui

2009-01-01

RNA modification, RNA interference, and RNA repair are important events in the cell. This thesis presents three projects related to these three fields. By using both biochemical and structural methods, we characterized enzymatic activities of pseudouridine synthase TruD, solved the structure of "A. aeolicus" GidA, and reconstituted a novel…

Microplate-based platform for combined chromatin and DNA methylation immunoprecipitation assays

PubMed Central

2011-01-01

Background The processes that compose expression of a given gene are far more complex than previously thought presenting unprecedented conceptual and mechanistic challenges that require development of new tools. Chromatin structure, which is regulated by DNA methylation and histone modification, is at the center of gene regulation. Immunoprecipitations of chromatin (ChIP) and methylated DNA (MeDIP) represent a major achievement in this area that allow researchers to probe chromatin modifications as well as specific protein-DNA interactions in vivo and to estimate the density of proteins at specific sites genome-wide. Although a critical component of chromatin structure, DNA methylation has often been studied independently of other chromatin events and transcription. Results To allow simultaneous measurements of DNA methylation with other genomic processes, we developed and validated a simple and easy-to-use high throughput microplate-based platform for analysis of DNA methylation. Compared to the traditional beads-based MeDIP the microplate MeDIP was more sensitive and had lower non-specific binding. We integrated the MeDIP method with a microplate ChIP assay which allows measurements of both DNA methylation and histone marks at the same time, Matrix ChIP-MeDIP platform. We illustrated several applications of this platform to relate DNA methylation, with chromatin and transcription events at selected genes in cultured cells, human cancer and in a model of diabetic kidney disease. Conclusion The high throughput capacity of Matrix ChIP-MeDIP to profile tens and potentially hundreds of different genomic events at the same time as DNA methylation represents a powerful platform to explore complex genomic mechanism at selected genes in cultured cells and in whole tissues. In this regard, Matrix ChIP-MeDIP should be useful to complement genome-wide studies where the rich chromatin and transcription database resources provide fruitful foundation to pursue mechanistic, functional and diagnostic information at genes of interest in health and disease. PMID:22098709

A study of the age attribute in a query tool for a clinical data warehouse.

PubMed

Scheufele, Elisabeth L; Scheufele, Elisabeth Lee; Dubey, Anil; Dubey, Anil Kumar; Murphy, Shawn N

2008-11-06

The RPDR, a clinical data warehouse with a user-friendly Querytool, allows researchers to perform studies on patient data. Currently, the RPDR represents age as the patient's age at the present time, which is problematic in situations where age at the time of the event is more appropriate. We will modify the Querytool to consider this by assessing the perception of age via survey, testing backend query solutions, and developing modifications based on these results.

Wounds due to a modified shot gun (home-made): a case report.

PubMed

Palimar, Vikram; Nayak, Vinod C; Arun, M; Kumar, Pradeep G; Bhagavath, Prashantha

2010-05-01

In a case of firearm fatality, the autopsy surgeon is required to opine as to the range of fire in addition to the cause of death which will help in reconstruction of the events. Problems may arise in estimating the range of fire based on wound ballistics when there is an alteration or modification in the internal ballistics. We encountered such a case in the department of Forensic Medicine, Kasturba Medical College, Manipal, which is discussed. Copyright (c) 2010. Published by Elsevier Ltd.

Recent findings and technological advances in phosphoproteomics for cells and tissues.

PubMed

von Stechow, Louise; Francavilla, Chiara; Olsen, Jesper V

2015-01-01

Site-specific phosphorylation is a fast and reversible covalent post-translational modification that is tightly regulated in cells. The cellular machinery of enzymes that write, erase and read these modifications (kinases, phosphatases and phospho-binding proteins) is frequently deregulated in different diseases, including cancer. Large-scale studies of phosphoproteins - termed phosphoproteomics - strongly rely on the use of high-performance mass spectrometric instrumentation. This powerful technology has been applied to study a great number of phosphorylation-based phenotypes. Nevertheless, many technical and biological challenges have to be overcome to identify biologically relevant phosphorylation sites in cells and tissues. This review describes different technological strategies to identify and quantify phosphorylation sites with high accuracy, without significant loss of analysis speed and reproducibility in tissues and cells. Moreover, computational tools for analysis, integration and biological interpretation of phosphorylation events are discussed.

In Utero Alcohol Exposure and the Alteration of Histone Marks in the Developing Fetus: An Epigenetic Phenomenon of Maternal Drinking

PubMed Central

Mandal, Chanchal; Halder, Debasish; Jung, Kyoung Hwa; Chai, Young Gyu

2017-01-01

Ethanol is well known for its teratogenic effects during fetal development. Maternal alcohol consumption allows the developing fetus to experience the detrimental effects of alcohol exposure. Alcohol-mediated teratogenic effects can vary based on the dosage and the length of exposure. The specific mechanism of action behind this teratogenic effect is still unknown. Previous reports demonstrated that alcohol participates in epigenetic alterations, especially histone modifications during fetal development. Additional research is necessary to understand the correlation between major epigenetic events and alcohol-mediated teratogenesis such as that observed in fetal alcohol spectrum disorder (FASD). Here, we attempted to collect all the available information concerning alcohol-mediated histone modifications during gestational fetal development. We hope that this review will aid researchers to further examine the issues associated with ethanol exposure. PMID:29104501

Modification of mesospheric OH and O3 during a measured highly relativistic electron precipitation event

NASA Technical Reports Server (NTRS)

Goldberg, R. A.; Jackman, C. H.; Backer, D. N.; Herrero, F. A.

1994-01-01

Highly relativistic electron precipitation events (HRE's) can provide a major source of energy affecting mesospheric constituents and ionization. Based on satellite data, these events are most pronounced near the minimum of the solar sunspot cycle, increasing in intensity, spectral hardness, and frequency of occurrence as the solar cycle declines. Since such events can be sustained up to several days, their integrated effect in the mesosphere can dominate over those of other energy sources such as relativistic electron precipitation events (REP's) and auroral precipitation. The energy deposition data to be discussed and analyzed were obtained by rocket at Poker Flat, Alaska, in May 1990 during a modest HRE observed at midday near the peak of the sunspot cycle. Using a NASA two dimensional model, significant enhancement of OH and depletion of O3 at 75 +/- 10 km altitude from the measured radiation are found. Estimates of enhanced effects were made for more intense HRE events, as might be expected during solar minimum. By causing O3 depletion, the electron precipitation can also regulate the penetration of solar UV radiation, which could affect the thermal properties of the mesosphere.

Epigenetic regulation in dental pulp inflammation

PubMed Central

Hui, T; Wang, C; Chen, D; Zheng, L; Huang, D; Ye, L

2016-01-01

Dental caries, trauma, and other possible factors could lead to injury of the dental pulp. Dental infection could result in immune and inflammatory responses mediated by molecular and cellular events and tissue breakdown. The inflammatory response of dental pulp could be regulated by genetic and epigenetic events. Epigenetic modifications play a fundamental role in gene expression. The epigenetic events might play critical roles in the inflammatory process of dental pulp injury. Major epigenetic events include methylation and acetylation of histones and regulatory factors, DNA methylation, and small non-coding RNAs. Infections and other environmental factors have profound effects on epigenetic modifications and trigger diseases. Despite growing evidences of literatures addressing the role of epigenetics in the field of medicine and biology, very little is known about the epigenetic pathways involved in dental pulp inflammation. This review summarized the current knowledge about epigenetic mechanisms during dental pulp inflammation. Progress in studies of epigenetic alterations during inflammatory response would provide opportunities for the development of efficient medications of epigenetic therapy for pulpitis. PMID:26901577

78 FR 69135 - Petitions for Modification of Application of Existing Mandatory Safety Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

..., because there is a chance that the water can become polluted from some external event such as a fire or...) The nature of any emergency itself could cause an external water supply to be polluted, choked, or... Affected: 30 CFR 75.1101-1(b) (Deluge-type water spray systems). Modification Request: The petitioner...

Evaluation of the natural history of patients who aspirate.

PubMed

Bock, Jonathan M; Varadarajan, Varun; Brawley, Mary C; Blumin, Joel H

2017-12-01

The natural clinical progression of aspiration to eventual pulmonary compromise is not well understood. We hypothesized that dietary modification recommendations, Penetration-Aspiration Scale (PAS) score, and dysphagia etiology would be associated with changes in time to first pulmonary event and overall survival for patients with documented aspiration on radiologic testing. This study identified a cohort of patients with detectable unsensed penetration or aspiration on videofluoroscopic swallowing study (VFSS), and followed this cohort over time for development of pulmonary events and death. We then evaluated the association of aspiration severity and dietary modification recommendations on incidence of these endpoints. Retrospective chart review. A total of 2,616 VFSS exam reports were reviewed from our institution performed between January 1, 2009 and December 31, 2010. Aspiration or unsensed penetration (PAS of 5 or greater) was detected in 564 (21.5%) of these patients, who were then included in the study cohort. Medical records were reviewed retrospectively for development of pulmonary events (pneumonia, pneumonitis, or other life-threatening pulmonary illness) and all-cause mortality for up to 54 months after initial VFSS. Univariate Kaplan-Meier analysis and multivariate Cox regression were performed for time to first pulmonary event and survival predicted by recommended diet, PAS score, and dysphagia etiology. Dysphagia etiology was highly associated with increased development of pulmonary events for some patients, especially those with generalized nonspecific dysphagia due to deconditioning or frailty (hazard ratio [HZ] vs. stroke 2.95, 95% confidence interval [CI]: 1.53-5.69, P = .001) and esophageal dysphagia (HZ: 2.66, 95% CI: 1.17-6.02, P = .019). Dysphagia etiology was also associated with increased mortality for patients with generalized nonspecific dysphagia due to deconditioning or frailty (HZ: 3.32, 95% CI: 2.0-5.52, P < .001), postsurgical patients (HZ: 1.73, 95% CI: 1.05-2.86, P = .032), and chronic neurologic disease (HZ: 1.87, 95% CI: 1.12-3.13, P = .017). Dietary modification recommendations at the time of VFSS (prohibition of oral intake or modification of food consistency) had no significant impact on time to first pulmonary event (P = .37) or survival (P = .17), whereas PAS score was associated with decreased time to first pulmonary event on univariate but not multivariate analysis (HZ for 1-point increase: 1.6, 95% CI: 0.99-1.36, P = .067). Kaplan-Meier estimate of overall 3-year mortality for this patient cohort was 39%. Etiology of dysphagia is associated with a higher mortality rate and development of pulmonary events in patients with unsensed penetration or aspiration on VFSS, especially for those patients with generalized deconditioning and frailty or esophageal dysphagia. Severity of aspiration as defined by PAS was not associated with altered overall survival. Recommendations for dietary modification to a nothing by mouth status or modified food consistency had no statistically significant association with development of pulmonary events or survival in patients with detectable unsensed penetration or aspiration on VFSS compared to full-diet recommendation. 4. Laryngoscope, 127:S1-S10, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Fetal heart rate deceleration detection using a discrete cosine transform implementation of singular spectrum analysis.

PubMed

Warrick, P A; Precup, D; Hamilton, E F; Kearney, R E

2007-01-01

To develop a singular-spectrum analysis (SSA) based change-point detection algorithm applicable to fetal heart rate (FHR) monitoring to improve the detection of deceleration events. We present a method for decomposing a signal into near-orthogonal components via the discrete cosine transform (DCT) and apply this in a novel online manner to change-point detection based on SSA. The SSA technique forms models of the underlying signal that can be compared over time; models that are sufficiently different indicate signal change points. To adapt the algorithm to deceleration detection where many successive similar change events can occur, we modify the standard SSA algorithm to hold the reference model constant under such conditions, an approach that we term "base-hold SSA". The algorithm is applied to a database of 15 FHR tracings that have been preprocessed to locate candidate decelerations and is compared to the markings of an expert obstetrician. Of the 528 true and 1285 false decelerations presented to the algorithm, the base-hold approach improved on standard SSA, reducing the number of missed decelerations from 64 to 49 (21.9%) while maintaining the same reduction in false-positives (278). The standard SSA assumption that changes are infrequent does not apply to FHR analysis where decelerations can occur successively and in close proximity; our base-hold SSA modification improves detection of these types of event series.

Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

PubMed Central

Naz, Anam; Obaid, Ayesha; Awan, Faryal M.; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad

2017-01-01

Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells. PMID:28932213

Concise review: managing genotoxicity in the therapeutic modification of stem cells.

PubMed

Baum, Christopher; Modlich, Ute; Göhring, Gudrun; Schlegelberger, Brigitte

2011-10-01

The therapeutic use of procedures for genetic stem cell modification is limited by potential adverse events related to uncontrolled mutagenesis. Prominent findings have been made in hematopoietic gene therapy, demonstrating the risk of clonal, potentially malignant outgrowth on the basis of mutations acquired during or after therapeutic genome modification. The incidence and the growth rate of insertional mutants have been linked to the "stemness" of the target cells and vector-related features such as the integration pattern, the architecture, and the exact content of transgene cassettes. Milieu factors supporting the survival and expansion of mutants may eventually allow oncogenic progression. Similar concerns apply for medicinal products based on pluripotent stem cells. Focusing on the genetic stress induced by insertional mutagenesis and culture adaptation, we propose four conclusions. (a) Mutations occurring in the production of stem cell-based medicines may be unavoidable and need to be classified according to their risk to trigger the formation of clones that are sufficiently long-lived and mitotically active to acquire secondary transforming mutations. (b) The development of rational prevention strategies depends upon the identification of the specific mutations forming such "dominant clones" (which can also be addressed as cancer stem cell precursors) and a better knowledge of the mechanisms underlying their creation, expansion, and homeostatic control. (c) Quantitative assay systems are required to assess the practical value of preventive actions. (d) Improved approaches for the genetic modification of stem cells can address all critical steps in the origin and growth control of mutants. Copyright © 2011 AlphaMed Press.

Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma.

PubMed

Naz, Anam; Obaid, Ayesha; Awan, Faryal M; Ikram, Aqsa; Ahmad, Jamil; Ali, Amjad

2017-01-01

Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

Sonic hedgehog multimerization: a self-organizing event driven by post-translational modifications?

PubMed

Koleva, Mirella V; Rothery, Stephen; Spitaler, Martin; Neil, Mark A A; Magee, Anthony I

2015-01-01

Sonic hedgehog (Shh) is a morphogen active during vertebrate development and tissue homeostasis in adulthood. Dysregulation of the Shh signalling pathway is known to incite carcinogenesis. Due to the highly lipophilic nature of this protein imparted by two post-translational modifications, Shh's method of transit through the aqueous extracellular milieu has been a long-standing conundrum, prompting the proposition of numerous hypotheses to explain the manner of its displacement from the surface of the producing cell. Detection of high molecular-weight complexes of Shh in the intercellular environment has indicated that the protein achieves this by accumulating into multimeric structures prior to release from producing cells. The mechanism of assembly of the multimers, however, has hitherto remained mysterious and contentious. Here, with the aid of high-resolution optical imaging and post-translational modification mutants of Shh, we show that the C-terminal cholesterol and the N-terminal palmitate adducts contribute to the assembly of large multimers and regulate their shape. Moreover, we show that small Shh multimers are produced in the absence of any lipid modifications. Based on an assessment of the distribution of various dimensional characteristics of individual Shh clusters, in parallel with deductions about the kinetics of release of the protein from the producing cells, we conclude that multimerization is driven by self-assembly underpinned by the law of mass action. We speculate that the lipid modifications augment the size of the multimolecular complexes through prolonging their association with the exoplasmic membrane.

Disturbance regime

Treesearch

F.N. Scatena; J.F. Blanco; K.H. Beard; R.B. Waide; A.E. Lugo; N. Brokaw; W.L. Silver; B.L. Haines; J.K. Zimmerman

2012-01-01

The Luquillo Mountains are affected by a wide array of environmental processes and distnrbances. Events that concurrently alter the environmental space of several different areas of the Luquillo Mountains occur every 2 to 5 years. Events such as hurricanes that cause widespread environmental modification occur once every 20 to 60 years. The most common disturbance-...

Association between sucrose intake and acute coronary event risk and effect modification by lifestyle factors: Malmö Diet and Cancer Cohort Study.

PubMed

Warfa, K; Drake, I; Wallström, P; Engström, G; Sonestedt, E

2016-11-01

Previous studies have suggested that a high intake of sugar-sweetened beverages is positively associated with the risk of a coronary event. However, a few studies have examined the association between sucrose (the most common extrinsic sugar in Sweden) and incident coronary events. The objective of the present study was to examine the associations between sucrose intake and coronary event risk and to determine whether these associations are specific to certain subgroups of the population (i.e. according to physical activity, obesity status, educational level, alcohol consumption, smoking habits, intake of fat and intake of fruits and vegetables). We performed a prospective analysis on 26 190 individuals (62 % women) free from diabetes and without a history of CVD from the Swedish population-based Malmö Diet and Cancer cohort. Over an average of 17 years of follow-up (457 131 person-years), 2493 incident cases of coronary events were identified. Sucrose intake was obtained from an interview-based diet history method, including 7-d records of prepared meals and cold beverages and a 168-item diet questionnaire covering other foods. Participants who consumed >15 % of their energy intake (E%) from sucrose showed a 37 (95 % CI 13, 66) % increased risk of a coronary event compared with the lowest sucrose consumers (<5 E%) after adjusting for potential confounders. The association was not modified by the selected lifestyle factors. The results indicated that sucrose consumption higher than 15 E% (5 % of this population) is associated with an increased risk of a coronary event.

Instrumentation and methodology for simultaneous excitation/detection of ions in an FTICR mass spectrometer

PubMed

Schmidt; Fiorentino; Arkin; Laude

2000-08-01

A method for direct and continuous detection of ion motion during different perturbation events of the fourier transform ion cyclotron resonance (FTICR) experiment is demonstrated. The modifications necessary to convert an ordinary FTICR cell into one capable of performing simultaneous excitation/detection (SED) using a capacitive network are outlined. With these modifications, a 200-fold reduction in the detection of the coupled excitation signal is achieved. This allows the unique ability not only to observe the response to the perturbation but to observe the perturbation event itself. SED is used successfully to monitor the ion cyclotron transient during single-frequency excitation, remeasurement and exciter-excite experiments.

Progressing From Initially Ambiguous Functional Analyses: Three Case Examples

PubMed Central

Tiger, Jeffrey H.; Fisher, Wayne W.; Toussaint, Karen A.; Kodak, Tiffany

2009-01-01

Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman (1982/1994). These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments. PMID:19233611

A new precipitation-based method of baseflow separation and event identification for small watersheds (<50 km2)

NASA Astrophysics Data System (ADS)

Koskelo, Antti I.; Fisher, Thomas R.; Utz, Ryan M.; Jordan, Thomas E.

2012-07-01

SummaryBaseflow separation methods are often impractical, require expensive materials and time-consuming methods, and/or are not designed for individual events in small watersheds. To provide a simple baseflow separation method for small watersheds, we describe a new precipitation-based technique known as the Sliding Average with Rain Record (SARR). The SARR uses rainfall data to justify each separation of the hydrograph. SARR has several advantages such as: it shows better consistency with the precipitation and discharge records, it is easier and more practical to implement, and it includes a method of event identification based on precipitation and quickflow response. SARR was derived from the United Kingdom Institute of Hydrology (UKIH) method with several key modifications to adapt it for small watersheds (<50 km2). We tested SARR on watersheds in the Choptank Basin on the Delmarva Peninsula (US Mid-Atlantic region) and compared the results with the UKIH method at the annual scale and the hydrochemical method at the individual event scale. Annually, SARR calculated a baseflow index that was ˜10% higher than the UKIH method due to the finer time step of SARR (1 d) compared to UKIH (5 d). At the watershed scale, hydric soils were an important driver of the annual baseflow index likely due to increased groundwater retention in hydric areas. At the event scale, SARR calculated less baseflow than the hydrochemical method, again because of the differences in time step (hourly for hydrochemical) and different definitions of baseflow. Both SARR and hydrochemical baseflow increased with event size, suggesting that baseflow contributions are more important during larger storms. To make SARR easy to implement, we have written a MatLab program to automate the calculations which requires only daily rainfall and daily flow data as inputs.

Performance of basic kinematic thresholds in the identification of crash and near-crash events within naturalistic driving data.

PubMed

Perez, Miguel A; Sudweeks, Jeremy D; Sears, Edie; Antin, Jonathan; Lee, Suzanne; Hankey, Jonathan M; Dingus, Thomas A

2017-06-01

Understanding causal factors for traffic safety-critical events (e.g., crashes and near-crashes) is an important step in reducing their frequency and severity. Naturalistic driving data offers unparalleled insight into these factors, but requires identification of situations where crashes are present within large volumes of data. Sensitivity and specificity of these identification approaches are key to minimizing the resources required to validate candidate crash events. This investigation used data from the Second Strategic Highway Research Program Naturalistic Driving Study (SHRP 2 NDS) and the Canada Naturalistic Driving Study (CNDS) to develop and validate different kinematic thresholds that can be used to detect crash events. Results indicate that the sensitivity of many of these approaches can be quite low, but can be improved by selecting particular threshold levels based on detection performance. Additional improvements in these approaches are possible, and may involve leveraging combinations of different detection approaches, including advanced statistical techniques and artificial intelligence approaches, additional parameter modifications, and automation of validation processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidence and predictors of regimen-modification from first-line antiretroviral therapy in Thailand: a cohort study.

PubMed

Tsuchiya, Naho; Pathipvanich, Panita; Wichukchinda, Nuanjun; Rojanawiwat, Archawin; Auwanit, Wattana; Ariyoshi, Koya; Sawanpanyalert, Pathom

2014-10-30

Antiretroviral therapy markedly reduced mortality in HIV-infected individuals. However, in the previous studies, up to 50% of patients are compelled to modify their regimen in middle and low-income countries where salvage drug is still limited. This cohort study aimed to investigate the incidence and predictors of regimen modification from the first-line antiretroviral regimen in northern Thailand. All HIV-infected patients starting antiretroviral therapy (ART) with generic drug (GPOvir®; stavudine, lamivudine and nevirapine) at a governmental hospital in northern Thailand from 2002 to 2007 were recruited. Baseline characteristics and detailed information of regimen modification until the end of 2010 were ascertained from cohort database and medical charts. As a potential genetic predictor of regimen modification, HLA B allele was determined by bead-based array hybridization (WAKFlow® HLA typing kit). We investigated predictors of the regimen modification using Cox's proportional hazard models. Of 979 patients, 914 were eligible for the analysis. The observed events of regimen modification was 377, corresponding to an incidence 13.8/100 person-year-observation (95% CI:12.5-15.3) over 2,728 person years (PY) follow up. The main reasons for regimen modification were adverse effects (73.5%), especially lipodystrophy (63.2%) followed by rash (17.7%). Sixty three patients (17.1%) changed the regimen due to treatment failure. 2% and 19% of patients had HLA-B*35:05 and B*4001, respectively. HLA-B*35:05 was independently associated with rash-related regimen modification (aHR 7.73, 95% CI:3.16-18.9) while female gender was associated with lipodystrophy (aHR 2.11, 95% CI:1.51-2.95). Female gender (aHR 0.54, 95% CI: 0.30-0.96), elder age (aHR 0.56, 95% CI: 0.32-0.99) and having HLA-B*40:01 (aHR 0.29, 95% CI: 0.10-0.82) were protective for treatment failure related modification. HLA-B*35:05 and female gender were strong predictors of regimen modification due to rash and lipodystrophy, respectively. Female gender, elder age, and having HLA-B*40:01 had protective effects on treatment failure-related regimen modification. This study provides further information of regimen modification for future tailored ART in Asia.

Genome-wide identification of sweet orange (Citrus sinensis) histone modification gene families and their expression analysis during the fruit development and fruit-blue mold infection process.

PubMed

Xu, Jidi; Xu, Haidan; Liu, Yuanlong; Wang, Xia; Xu, Qiang; Deng, Xiuxin

2015-01-01

In eukaryotes, histone acetylation and methylation have been known to be involved in regulating diverse developmental processes and plant defense. These histone modification events are controlled by a series of histone modification gene families. To date, there is no study regarding genome-wide characterization of histone modification related genes in citrus species. Based on the two recent sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis histone modification genes), including 47 CsHMTs (histone methyltransferase genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were identified. These genes were categorized to 11 gene families. A comprehensive analysis of these 11 gene families was performed with chromosome locations, phylogenetic comparison, gene structures, and conserved domain compositions of proteins. In order to gain an insight into the potential roles of these genes in citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were selected to further analyze their expression profiles at six stages of fruit development. Interestingly, a numbers of genes were expressed highly in flesh of ripening fruit and some of them showed the increasing expression levels along with the fruit development. Furthermore, we analyzed the expression patterns of all 136 CsHMs response to the infection of blue mold (Penicillium digitatum), which is the most devastating pathogen in citrus post-harvest process. The results indicated that 20 of them showed the strong alterations of their expression levels during the fruit-pathogen infection. In conclusion, this study presents a comprehensive analysis of the histone modification gene families in sweet orange and further elucidates their behaviors during the fruit development and the blue mold infection responses.

78 FR 26786 - 510(k) Device Modifications: Deciding When To Submit a 510(k) for a Change to an Existing Device...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... test protocols that will be used to examine those specifications pre- and post-modification, within the... information after May 31, 2013. If you have never attended a Connect Pro event before, test your connection at https://collaboration.fda.gov/common/help/en/support/meeting_test.htm . To get a quick overview of the...

Early events in copper-ion catalyzed oxidation of α-synuclein.

PubMed

Tiwari, Manish K; Leinisch, Fabian; Sahin, Cagla; Møller, Ian Max; Otzen, Daniel E; Davies, Michael J; Bjerrum, Morten J

2018-04-22

Previous studies on metal-ion catalyzed oxidation of α-synuclein oxidation have mostly used conditions that result in extensive modification precluding an understanding of the early events in this process. In this study, we have examined time-dependent oxidative events related to α-synuclein modification using six different molar ratios of Cu 2+ /H 2 O 2 /protein and Cu 2+ /H 2 O 2 /ascorbate/protein resulting in mild to moderate extents of oxidation. For a Cu 2+ /H 2 O 2 /protein molar ratio of 2.3:7.8:1 only low levels of carbonyls were detected (0.078 carbonyls per protein), whereas a molar ratio of 4.7:15.6:1 gave 0.22 carbonyls per α-synuclein within 15 min. With the latter conditions, rapid conversion of 3 out of 4 methionines (Met) to methionine sulfoxide, and 2 out of 4 tyrosines (Tyr) were converted to products including inter- and intra-molecular dityrosine cross-links and protein oligomers, as determined by SDS-PAGE and Western blot analysis. Limited histidine (His) modification was observed. The rapid formation of dityrosine cross-links was confirmed by fluorescence and mass-spectrometry. These data indicate that Met and Tyr oxidation are early events in Cu 2+ /H 2 O 2 -mediated damage, with carbonyl formation being a minor process. With the Cu 2+ /H 2 O 2 /ascorbate system, rapid protein carbonyl formation was detected with the first 5 min, but after this time point, little additional carbonyl formation was detected. With this system, lower levels of Met and Tyr oxidation were detected (2 Met and 1 Tyr modified with a Cu 2+ /H 2 O 2 /ascorbate/protein ratio of 2.3:7.8:7.8:1), but greater His oxidation. Only low levels of intra- dityrosine cross-links and no inter- dityrosine oligomers were detected under these conditions, suggesting that ascorbate limits Cu 2+ /H 2 O 2 -induced α-synuclein modification. Copyright © 2018. Published by Elsevier Inc.

Basic Mechanics of DNA Methylation and the Unique Landscape of the DNA Methylome in Metal-Induced Carcinogenesis

PubMed Central

Brocato, Jason; Costa, Max

2013-01-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypomethylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance. PMID:23844698

Basic mechanics of DNA methylation and the unique landscape of the DNA methylome in metal-induced carcinogenesis.

PubMed

Brocato, Jason; Costa, Max

2013-07-01

DNA methylation plays an intricate role in the regulation of gene expression and events that compromise the integrity of the methylome may potentially contribute to disease development. DNA methylation is a reversible and regulatory modification that elicits a cascade of events leading to chromatin condensation and gene silencing. In general, normal cells are characterized by gene-specific hypomethylation and global hypermethylation, while cancer cells portray a reverse profile to this norm. The unique methylome displayed in cancer cells is induced after exposure to carcinogenic metals such as nickel, arsenic, cadmium, and chromium (VI). These metals alter the DNA methylation profile by provoking both hyper- and hypo-methylation events. The metal-stimulated deviations to the methylome are possible mechanisms for metal-induced carcinogenesis and may provide potential biomarkers for cancer detection. Development of therapies based on the cancer methylome requires further research including human studies that supply results with larger impact and higher human relevance.

Relationship between Physician-Adjudicated Adverse Events and Patient-Reported Health-Related Quality of Life in a Phase II Clinical Trial (NCT01143402) of Patients with Metastatic Uveal Melanoma*

PubMed Central

Atkinson, Thomas M.; Hay, Jennifer L.; Shoushtari, Alexander; Li, Yuelin; Paucar, Daniel J.; Smith, Sloane C.; Kudchadkar, Ragini R.; Doyle, Austin; Sosman, Jeffrey A.; Quevedo, Jorge Fernando; Milhem, Mohammed M.; Joshua, Anthony M.; Linette, Gerald P.; Gajewski, Thomas F.; Lutzky, Jose; Lawson, David H.; Lao, Christopher D.; Flynn, Patrick J.; Albertini, Mark R.; Sato, Takami; Lewis, Karl; Marr, Brian; Abramson, David H.; Dickson, Mark Andrew; Schwartz, Gary K.; Carvajal, Richard D.

2016-01-01

Purpose Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the Common Terminology Criteria for Adverse Events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data is becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. Methods Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n=118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications. Results Ninety-four percent had a CTCAE grade ≥ 1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r=0.31, p<0.01) and end of treatment (r=0.42, p<0.05). There were no significant correlations between need for dose modification and HRQoL scores. Conclusions Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct. PMID:27921276

Relationship between physician-adjudicated adverse events and patient-reported health-related quality of life in a phase II clinical trial (NCT01143402) of patients with metastatic uveal melanoma.

PubMed

Atkinson, Thomas M; Hay, Jennifer L; Shoushtari, Alexander; Li, Yuelin; Paucar, Daniel J; Smith, Sloane C; Kudchadkar, Ragini R; Doyle, Austin; Sosman, Jeffrey A; Quevedo, Jorge Fernando; Milhem, Mohammed M; Joshua, Anthony M; Linette, Gerald P; Gajewski, Thomas F; Lutzky, Jose; Lawson, David H; Lao, Christopher D; Flynn, Patrick J; Albertini, Mark R; Sato, Takami; Lewis, Karl; Marr, Brian; Abramson, David H; Dickson, Mark Andrew; Schwartz, Gary K; Carvajal, Richard D

2017-03-01

Clinical trials commonly use physician-adjudicated adverse event (AE) assessment via the common terminology criteria for adverse events (CTCAE) for decision-making. Patient-reported health-related quality of life (HRQoL) data are becoming more frequent in oncology; however, the relationship between physician-adjudicated AE assessment and HRQoL is understudied. Data from a phase II trial (clinicaltrials.gov identifier: NCT01143402) where patients with metastatic uveal melanoma were randomized to receive selumetinib, an oral MEK inhibitor, or chemotherapy were analyzed. Patients reported HRQoL at baseline, after 1 month, and end of treatment (n = 118), whereas physicians adjudicated AEs via CTCAE. Mean HRQoL scores were compared between patient randomization arms, as well as between those patients who did/did not receive dose modifications. Ninety-four percent had a CTCAE grade ≥1 for at least one treatment-associated AE, with 18% undergoing dose modification due to toxicity. Mean HRQoL scores did not significantly differ at each of the three time points. Patient and physician-adjudicated reports of nausea were significantly correlated at the start (r = 0.31, p < 0.01) and end of treatment (r = 0.42, p < 0.05). There were no significant correlations between need for dose modification and HRQoL scores. Despite the high rate of physician-adjudicated AEs and need for dose modifications with selumetinib, patient-reported HRQoL was not impacted by treatment. Since HRQoL did not differ in the subgroup of patients who received dosage reductions due to AEs, patients may be willing to tolerate select AEs without dose modification (if medically appropriate). More research is needed to determine how to best integrate HRQoL data into clinical trial conduct.

Jet-hadron correlations relative to the event plane at the LHC with ALICE

NASA Astrophysics Data System (ADS)

Mazer, Joel; Alice Collaboration

2017-11-01

In ultra relativistic heavy-ion collisions at the Large Hadron Collider (LHC), conditions are met to produce a hot, dense and strongly interacting medium known as the Quark Gluon Plasma (QGP). Quarks and gluons from incoming nuclei collide to produce partons at high momenta early in the collisions. By fragmenting into collimated sprays of hadrons, these partons form 'jets'. The outgoing partons scatter and interact with the medium, leading to a manifestation of medium modifications of jets in the final state, known as jet quenching. Within the framework of perturbative QCD, jet production is well understood in pp collisions. We use jets measured in pp interactions as a baseline reference for comparing to heavy-ion collision systems to detect and study jet quenching. The jet quenching mechanism can be studied through the angular correlations of jets with charged hadrons and is examined in transverse momentum (pT) bins of the jets, pT bins of the associated hadrons, and as a function of collision centrality. A robust and precise background subtraction method is used in this analysis to remove the complex, flow dominated, heavy-ion background. The analysis of angular correlations for different orientations of the jet relative to the event plane allows for the study of the path-length dependence of medium modifications to jets. The event plane dependence of azimuthal angular correlations of charged hadrons with respect to the axis of an R = 0.2 reconstructed full (charged + neutral) jet in Pb-Pb collisions at √{sNN} = 2.76 TeV in ALICE is presented. Results are compared for three angular bins of the jet relative to the event plane in mid-peripheral events. The yields relative to the event plane are presented and then quantified through yield ratio calculations. The results show no significant path-length dependence on the medium modifications.

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 2 2012-10-01 2012-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 2 2013-10-01 2013-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 2 2011-10-01 2011-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

42 CFR 412.72 - Modification of base-year costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 2 2010-10-01 2010-10-01 false Modification of base-year costs. 412.72 Section 412... Modification of base-year costs. (a) Bases for modification of base-year costs. Base-year costs as determined... before November 16, 1983 has until November 15, 1983 to request its intermediary to reestimate its base...

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

Kyriakou, Ioanna; Emfietzoglou, Dimitris; Nojeh, Alireza

A systematic study of electron-beam penetration and backscattering in multi-walled carbon nanotube (MWCNT) materials for beam energies of {approx}0.3 to 30 keV is presented based on event-by-event Monte Carlo simulation of electron trajectories using state-of-the-art scattering cross sections. The importance of different analytic approximations for computing the elastic and inelastic electron-scattering cross sections for MWCNTs is emphasized. We offer a simple parameterization for the total and differential elastic-scattering Mott cross section, using appropriate modifications to the Browning formula and the Thomas-Fermi screening parameter. A discrete-energy-loss approach to inelastic scattering based on dielectric theory is adopted using different descriptions of themore » differential cross section. The sensitivity of electron penetration and backscattering parameters to the underlying scattering models is examined. Our simulations confirm the recent experimental backscattering data on MWCNT forests and, in particular, the steep increase of the backscattering yield at sub-keV energies as well as the sidewalls escape effect at high-beam energies.« less

Gender-Based Differences in Outcomes After Orbital Atherectomy for the Treatment of De Novo Severely Calcified Coronary Lesions.

PubMed

Lee, Michael S; Shlofmitz, Evan; Mansourian, Pejman; Sethi, Sanjum; Shlofmitz, Richard A

2016-11-01

We evaluated the relationship between gender and angiographic and clinical outcomes in patients with severely calcified lesions who underwent orbital atherectomy. Female gender is associated with increased risk of adverse clinical events after percutaneous coronary intervention (PCI). Severe coronary artery calcification increases the complexity of PCI and increases the risk of adverse cardiac events. Orbital atherectomy is effective in plaque modification, which facilitates stent delivery and expansion. Whether gender differences exist after orbital atherectomy is unclear. Our analysis retrospectively analyzed 458 consecutive real-world patients (314 males and 144 females) from three centers who underwent orbital atherectomy. The primary endpoint was the major adverse cardiac and cerebrovascular event (MACCE) rate, defined as the composite of death, myocardial infarction (MI), target-vessel revascularization (TVR), and stroke, at 30 days. The primary endpoint of MACCE was low and similar in females and males (0.7% vs 2.9%; P=.14). The individual endpoints of death (0.7% vs 1.6%; P=.43), MI (0.7% vs 1.3%; P=.58), TVR (0% vs 0%; P>.99), and stroke (0% vs 0.3%; P=.50) were low in both groups and did not differ. Angiographic complications were low: perforation (0.8% vs 0.7%; P>.90), dissection (0.8% vs 1.1%; P=.80), and no-reflow (0.8% vs 0.7%; P>.90). Plaque modification with orbital atherectomy was safe and provided similar angiographic and clinical outcomes between females and males. Randomized trials with longer-term follow-up are needed to support our results.

Homogeneous screening assay for human tankyrase.

PubMed

Narwal, Mohit; Fallarero, Adyary; Vuorela, Pia; Lehtiö, Lari

2012-06-01

Tankyrase, a member of human PARP protein superfamily, catalyzes a covalent post-translational modification of substrate proteins. This modification, poly(ADP-ribos)ylation, leads to changes in protein interactions and modifies downstream signaling events. Tankyrase 1 is a potential drug target due to its functions in telomere homeostasis and in Wnt signaling. We describe here optimization and application of an activity-based homogenous assay for tankyrase inhibitors in a high-throughput screening format. The method measures the consumption of substrate by the chemical conversion of the remaining NAD(+) into a stable fluorescent condensation product. Conditions were optimized to measure the enzymatic auto-modification of a recombinant catalytic fragment of tankyrase 1. The fluorescence assay is inexpensive, operationally easy and performs well according to the statistical analysis (Z'= 0.7). A validatory screen with a natural product library confirmed suitability of the assay for finding new tankyrase inhibitors. Flavone was the most potent (IC(50)=325 nM) hit from the natural compounds. A flavone derivative, apigenin, and isopropyl gallate showed potency on the micromolar range, but displayed over 30-fold selectivity for tankyrase over the studied isoenzymes PARP1 and PARP2. The assay is robust and will be useful for screening new tankyrase inhibitors.

Midcourse correction to a clinical trial when the event rate is underestimated: the Look AHEAD (Action for Health in Diabetes) Study.

PubMed

Brancati, Frederick L; Evans, Mary; Furberg, Curt D; Geller, Nancy; Haffner, Steven; Kahn, Steven E; Kaufmann, Peter G; Lewis, Cora E; Nathan, David M; Pitt, Bertram; Safford, Monika M

2012-02-01

The Look AHEAD (Action for Health in Diabetes) Study is a long-term clinical trial that aims to determine the cardiovascular disease (CVD) benefits of an intensive lifestyle intervention (ILI) in obese adults with type 2 diabetes. The study was designed to have 90% statistical power to detect an 18% reduction in the CVD event rate in the ILI Group compared to the Diabetes Support and Education (DSE) Group over 10.5 years of follow-up. The original power calculations were based on an expected CVD rate of 3.125% per year in the DSE group; however, a much lower-than-expected rate in the first 2 years of follow-up prompted the Data and Safety Monitoring Board (DSMB) to recommend that the Steering Committee undertake a formal blinded evaluation of these design considerations. The Steering Committee created an Endpoint Working Group (EPWG) that consisted of individuals masked to study data to examine relevant issues. The EPWG considered two primary options: (1) expanding the definition of the primary endpoint and (2) extending follow-up of participants. Ultimately, the EPWG recommended that the Look AHEAD Steering Committee approve both strategies. The DSMB accepted these modifications, rather than recommending that the trial continue with inadequate statistical power. Trialists sometimes need to modify endpoints after launch. This decision should be well justified and should be made by individuals who are fully masked to interim results that could introduce bias. This article describes this process in the Look AHEAD study and places it in the context of recent articles on endpoint modification and recent trials that reported endpoint modification.

Monte-Carlo Event Generators for Jet Modification in d(p)-A and A-A Collisions

NASA Astrophysics Data System (ADS)

Kordell, Michael C., III

This work outlines methods to use jet simulations to study both initial and final state nuclear effects in heavy-ion collisions. To study the initial state of heavy-ion collisions, the production of jets and high momentum hadrons from jets, produced in deuteron (d)-Au collisions at the relativistic heavy-ion collider (RHIC) and proton (p)- Pb collisions at the large hadron collider (LHC) are studied as a function of centrality, a measure of the impact parameter of the collision. A modified version of the event generator PYTHIA, widely used to simulate p-p collisions, is used in conjunction with a nuclear Monte-Carlo event generator which simulates the locations of the nucleons within a large nucleus. It is demonstrated how events with a hard jet may be simulated, in such a way that the parton distribution function of the projectile is frozen during its interaction with the extended nucleus. Using this approach, it is demonstrated that the puzzling enhancement seen in peripheral events at RHIC and the LHC, as well as the suppression seen in central events at the LHC are mainly due to mis-binning of central and semi-central events, containing a jet, as peripheral events. This occurs due to the suppression of soft particle production away from the jet, caused by the depletion of energy available in a nucleon of the deuteron (in d-Au at RHIC) or in the proton (in p-Pb at LHC), after the production of a hard jet. In conclusion, partonic correlations built out of simple energy conservation are responsible for such an effect, though these are sampled at the hard scale of jet production and, as such, represent smaller states. To study final state nuclear effects, the modification of hard jets in the Quark Gluon Plasma (QGP) is simulated using the MATTER event generator. Based on the higher twist formalism of energy loss, the MATTER event generator simulates the evolution of highly virtual partons through a medium. These partons sampled from an underlying PYTHIA kernel undergo splitting through a combination of vacuum and medium induced emission. The momentum exchange with the medium is simulated via the jet transport coefficient q̂, which is assumed to scale with the entropy density at a given location in the medium. The entropy density is obtained from a relativistic viscous fluid dynamics simulation (VISH2+1D) in 2+1 space time dimensions. Results for jet and hadron observables are presented using an independent fragmentation model.

High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome.

PubMed

Worm, Signe W; Friis-Møller, Nina; Bruyand, Mathias; D'Arminio Monforte, Antonella; Rickenbach, Martin; Reiss, Peter; El-Sadr, Wafaa; Phillips, Andrew; Lundgren, Jens; Sabin, Caroline

2010-01-28

This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time. We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome was modified to take account of the use of lipid-lowering and antihypertensive medication, measurement variability and missing values, and assessed the impact of these modifications on the estimated prevalence. For all definitions considered, there was an increasing prevalence of the metabolic syndrome over time, although the prevalence estimates themselves varied widely. Using our primary definition, we found an increase in prevalence from 19.4% in 2000/2001 to 41.6% in 2006/2007. Modification of the definition to incorporate antihypertensive and lipid-lowering medication had relatively little impact on the prevalence estimates, as did modification to allow for missing data. In contrast, modification to allow the metabolic syndrome to be reversible and to allow for measurement variability lowered prevalence estimates substantially. The prevalence of the metabolic syndrome in cohort studies is largely based on the use of nonstandardized measurements as they are captured in daily clinical care. As a result, bias is easily introduced, particularly when measurements are both highly variable and may be missing. We suggest that the prevalence of the metabolic syndrome in cohort studies should be based on two consecutive measurements of the laboratory components in the syndrome definition.

Interplay between the miRNome and the epigenetic machinery: Implications in health and disease.

PubMed

Poddar, Shagun; Kesharwani, Devesh; Datta, Malabika

2017-11-01

Epigenetics refers to functionally relevant genomic changes that do not involve changes in the basic nucleotide sequence. Majorly, these are of two types: DNA methylation and histone modifications. Small RNA molecules called miRNAs are often thought to mediate post-transcriptional epigenetic changes by mRNA degradation or translational attenuation. While DNA methylation and histone modifications have their own independent effects on various cellular events, several reports are suggestive of an obvious interplay between these phenomena and the miRNA regulatory program within the cell. Several miRNAs like miR-375, members of miR-29 family, miR-34, miR-200, and others are regulated by DNA methylation and histone modifications in various types of cancers and metabolic diseases. On the other hand, miRNAs like miR-449a, miR-148, miR-101, miR-214, and miR-128 target members of the epigenetic machinery and their dysregulation leads to diverse cellular aberrations. In spite of being independent cellular events, emergence of such reports that suggest a connection between DNA methylation, histone modification, and miRNA function in several diseases indicate that this connecting axis offers a valuable target with great therapeutic potential that might be exploited for disease management. We review the current status of crosstalk between the major epigenetic modifications and the miRNA machinery and discuss this in the context of health and disease. © 2017 Wiley Periodicals, Inc.

Low incidence of SNVs and indels in trio genomes of Cas9-mediated multiplex edited sheep.

PubMed

Wang, Xiaolong; Liu, Jing; Niu, Yiyuan; Li, Yan; Zhou, Shiwei; Li, Chao; Ma, Baohua; Kou, Qifang; Petersen, Bjoern; Sonstegard, Tad; Huang, Xingxu; Jiang, Yu; Chen, Yulin

2018-05-25

The simplicity of the CRISPR/Cas9 system has enabled its widespread applications in generating animal models, functional genomic screening and in treating genetic and infectious diseases. However, unintended mutations produced by off-target CRISPR/Cas9 nuclease activity may lead to negative consequences. Especially, a very recent study found that gene editing can introduce hundreds of unintended mutations into the genome, and have attracted wide attention. To address the off-target concerns, urgent characterization of the CRISPR/Cas9-mediated off-target mutagenesis is highly anticipated. Here we took advantage of our previously generated gene-edited sheep and performed family trio-based whole genome sequencing which is capable of discriminating variants in the edited progenies that are inherited, naturally generated, or induced by genetic modification. Three family trios were re-sequenced at a high average depth of genomic coverage (~ 25.8×). After developing a pipeline to comprehensively analyze the sequence data for de novo single nucleotide variants, indels and structural variations from the genome; we only found a single unintended event in the form of a 2.4 kb inversion induced by site-specific double-strand breaks between two sgRNA targeting sites at the MSTN locus with a low incidence. We provide the first report on the fidelity of CRISPR-based modification for sheep genomes targeted simultaneously for gene breaks at three coding sequence locations. The trio-based sequencing approach revealed almost negligible off-target modifications, providing timely evidences of the safe application of genome editing in vivo with CRISPR/Cas9.

Age-related carbonylation of fibrocartilage structural proteins drives tissue degenerative modification.

PubMed

Scharf, Brian; Clement, Cristina C; Yodmuang, Supansa; Urbanska, Aleksandra M; Suadicani, Sylvia O; Aphkhazava, David; Thi, Mia M; Perino, Giorgio; Hardin, John A; Cobelli, Neil; Vunjak-Novakovic, Gordana; Santambrogio, Laura

2013-07-25

Aging-related oxidative stress has been linked to degenerative modifications in different organs and tissues. Using redox proteomic analysis and illustrative tandem mass spectrometry mapping, we demonstrate oxidative posttranslational modifications in structural proteins of intervertebral discs (IVDs) isolated from aging mice. Increased protein carbonylation was associated with protein fragmentation and aggregation. Complementing these findings, a significant loss of elasticity and increased stiffness was measured in fibrocartilage from aging mice. Studies using circular dichroism and intrinsic tryptophan fluorescence revealed a significant loss of secondary and tertiary structures of purified collagens following oxidation. Collagen unfolding and oxidation promoted both nonenzymatic and enzymatic degradation. Importantly, induction of oxidative modification in healthy fibrocartilage recapitulated the biochemical and biophysical modifications observed in the aging IVD. Together, these results suggest that protein carbonylation, glycation, and lipoxidation could be early events in promoting IVD degenerative changes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer.

PubMed

Kabekkodu, Shama Prasada; Chakrabarty, Sanjiban; Ghosh, Supriti; Brand, Angela; Satyamoorthy, Kapaettu

2017-01-01

Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events. Recent studies have also mapped these epigenetic modification and pathways leading to carcinogenesis. Discovery of drugs that target proteins/enzymes in the epigenetic pathways may provide better therapeutic opportunities, and identification of such modulators for DNA methylation, histone modifications, and expression of noncoding RNAs for several cancer types is underway. In this review, we provide a detailed description of recent developments in the field of epigenetics and its impact on personalized medicine to manage cervical cancer. © 2017 S. Karger AG, Basel.

Measurement of dijet k T in p–Pb collisions at s NN = 5.02 TeV

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

Adam, J.

A measurement of dijet correlations in p–Pb collisions at √s NN = 5.02 TeV with the ALICE detector is presented. Jets are reconstructed from charged particles measured in the central tracking detectors and neutral energy deposited in the electromagnetic calorimeter. The transverse momentum of the full jet (clustered from charged and neutral constituents) and charged jet (clustered from charged particles only) is corrected event-by-event for the contribution of the underlying event, while corrections for underlying event fluctuations and finite detector resolution are applied on an inclusive basis. A projection of the dijet transverse momentum, k Ty = p T,jet ch+nesin(Δmore » φdijet) with Δ φdijet the azimuthal angle between a full and charged jet and p T,jet ch+ne the transverse momentum of the full jet, is used to study nuclear matter effects in p–Pb collisions. This observable is sensitive to the acoplanarity of dijet production and its potential modification in p–Pb collisions with respect to pp collisions. Here, measurements of the dijet k Ty as a function of the transverse momentum of the full and recoil charged jet, and the event multiplicity are presented. No significant modification of k Ty due to nuclear matter effects in p–Pb collisions with respect to the event multiplicity or a PYTHIA8 reference is observed.« less

Measurement of dijet k T in p–Pb collisions at s NN = 5.02 TeV

DOE PAGES

Adam, J.

2015-05-19

A measurement of dijet correlations in p–Pb collisions at √s NN = 5.02 TeV with the ALICE detector is presented. Jets are reconstructed from charged particles measured in the central tracking detectors and neutral energy deposited in the electromagnetic calorimeter. The transverse momentum of the full jet (clustered from charged and neutral constituents) and charged jet (clustered from charged particles only) is corrected event-by-event for the contribution of the underlying event, while corrections for underlying event fluctuations and finite detector resolution are applied on an inclusive basis. A projection of the dijet transverse momentum, k Ty = p T,jet ch+nesin(Δmore » φdijet) with Δ φdijet the azimuthal angle between a full and charged jet and p T,jet ch+ne the transverse momentum of the full jet, is used to study nuclear matter effects in p–Pb collisions. This observable is sensitive to the acoplanarity of dijet production and its potential modification in p–Pb collisions with respect to pp collisions. Here, measurements of the dijet k Ty as a function of the transverse momentum of the full and recoil charged jet, and the event multiplicity are presented. No significant modification of k Ty due to nuclear matter effects in p–Pb collisions with respect to the event multiplicity or a PYTHIA8 reference is observed.« less

Peritraumatic panic attacks and health outcomes two years after psychological trauma: implications for intervention and research.

PubMed

Boscarino, Joseph A; Adams, Richard E

2009-05-15

Several studies have suggested that experiencing a peritraumatic panic attack (PPA) during a traumatic event predicts future mental health status. Some investigators have suggested that this finding has psychotherapeutic significance. We assessed the hypothesis that PPA was not related to longer-term health status after event exposure, once background confounders were controlled. In our study we assessed exposure to the World Trade Center disaster (WTCD) and other negative life events, demographic factors, social support, self-esteem, and panic attack onset in predicting health outcome among 1681 New York City residents 2 years after the attack. Initial bivariate results indicated that a PPA was related to a number of adverse outcomes 2 years after the WTCD, including posttraumatic stress disorder, depression, poor physical health, anxiety, binge drinking, and mental health treatment seeking. However, when multivariate (MV) models were estimated adjusting for potential confounders, most of these associations were either non-significant or substantially reduced. Contrary to previous predictions, these MV models revealed that recent negative life events and current self-esteem at follow-up were the best predictors of health outcomes, not PPA. Although post-trauma interventions may target individuals who experienced PPA after traumatic exposures, reducing the long-term health consequences following such exposures based on PPA alone may be problematic. Modifications of psychopathology constructs based on the reported correlation between PPA and post-trauma outcomes may be premature.

Systematic inference of functional phosphorylation events in yeast metabolism.

PubMed

Chen, Yu; Wang, Yonghong; Nielsen, Jens

2017-07-01

Protein phosphorylation is a post-translational modification that affects proteins by changing their structure and conformation in a rapid and reversible way, and it is an important mechanism for metabolic regulation in cells. Phosphoproteomics enables high-throughput identification of phosphorylation events on metabolic enzymes, but identifying functional phosphorylation events still requires more detailed biochemical characterization. Therefore, development of computational methods for investigating unknown functions of a large number of phosphorylation events identified by phosphoproteomics has received increased attention. We developed a mathematical framework that describes the relationship between phosphorylation level of a metabolic enzyme and the corresponding flux through the enzyme. Using this framework, it is possible to quantitatively estimate contribution of phosphorylation events to flux changes. We showed that phosphorylation regulation analysis, combined with a systematic workflow and correlation analysis, can be used for inference of functional phosphorylation events in steady and dynamic conditions, respectively. Using this analysis, we assigned functionality to phosphorylation events of 17 metabolic enzymes in the yeast Saccharomyces cerevisiae , among which 10 are novel. Phosphorylation regulation analysis cannot only be extended for inference of other functional post-translational modifications but also be a promising scaffold for multi-omics data integration in systems biology. Matlab codes for flux balance analysis in this study are available in Supplementary material. yhwang@ecust.edu.cn or nielsenj@chalmers.se. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes

PubMed Central

Chand, Mahesh Kumar; Nirwan, Neha; Diffin, Fiona M.; van Aelst, Kara; Kulkarni, Manasi; Pernstich, Christian; Szczelkun, Mark D.; Saikrishnan, Kayarat

2015-01-01

Endonucleolytic double-strand DNA break production requires separate strand cleavage events. Although catalytic mechanisms for simple dimeric endonucleases are available, there are many complex nuclease machines which are poorly understood in comparison. Here we studied the single polypeptide Type ISP restriction-modification (RM) enzymes, which cleave random DNA between distant target sites when two enzymes collide following convergent ATP-driven translocation. We report the 2.7 Angstroms resolution X-ray crystal structure of a Type ISP enzyme-DNA complex, revealing that both the helicase-like ATPase and nuclease are unexpectedly located upstream of the direction of translocation, inconsistent with simple nuclease domain-dimerization. Using single-molecule and biochemical techniques, we demonstrate that each ATPase remodels its DNA-protein complex and translocates along DNA without looping it, leading to a collision complex where the nuclease domains are distal. Sequencing of single cleavage events suggests a previously undescribed endonuclease model, where multiple, stochastic strand nicking events combine to produce DNA scission. PMID:26389736

Modification of the SAS4A Safety Analysis Code for Integration with the ADAPT Discrete Dynamic Event Tree Framework.

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

Jankovsky, Zachary Kyle; Denman, Matthew R.

It is difficult to assess the consequences of a transient in a sodium-cooled fast reactor (SFR) using traditional probabilistic risk assessment (PRA) methods, as numerous safety-related sys- tems have passive characteristics. Often there is significant dependence on the value of con- tinuous stochastic parameters rather than binary success/failure determinations. One form of dynamic PRA uses a system simulator to represent the progression of a transient, tracking events through time in a discrete dynamic event tree (DDET). In order to function in a DDET environment, a simulator must have characteristics that make it amenable to changing physical parameters midway through themore » analysis. The SAS4A SFR system analysis code did not have these characteristics as received. This report describes the code modifications made to allow dynamic operation as well as the linking to a Sandia DDET driver code. A test case is briefly described to demonstrate the utility of the changes.« less

Mapping Base Modifications in DNA by Transverse-Current Sequencing

NASA Astrophysics Data System (ADS)

Alvarez, Jose R.; Skachkov, Dmitry; Massey, Steven E.; Kalitsov, Alan; Velev, Julian P.

2018-02-01

Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.

Field Verification Program (Upland Disposal): Prediction of Surface Runoff Water Quality from Black Rock Harbor Dredged Material Placed in an Upland Disposal Site.

DTIC Science & Technology

1987-03-01

Simulator was similar to the original rotating disk-type rainfall simulator but had several important design modifications ( Westerdahl and Skogerboe...exist- ing vegetation on the soil surface ( Westerdahl and Skogerboe 1982). A multiple-peaked natural storm event was selected from field data and pro... Westerdahl and Skogerboe 1982) and has been used as a standard storm event for comparison to natural storm events (Laws and Parsons 1943). Similar

Runoff as a factor in USLE/RUSLE technology

NASA Astrophysics Data System (ADS)

Kinnell, Peter

2014-05-01

Modelling erosion for prediction purposes started with the development of the Universal Soil Loss Equation the focus of which was the prediction of long term (~20) average annul soil loss from field sized areas. That purpose has been maintained in the subsequent revision RUSLE, the most widely used erosion prediction model in the world. The lack of ability to predict short term soil loss saw the development of so-called process based models like WEPP and EUROSEM which focussed on predicting event erosion but failed to improve the prediction of long term erosion where the RUSLE worked well. One of the features of erosion recognised in the so-called process based modes is the fact that runoff is a primary factor in rainfall erosion and some modifications of USLE/RUSLE model have been proposed have included runoff as in independent factor in determining event erosivity. However, these models have ignored fundamental mathematical rules. The USLE-M which replaces the EI30 index by the product of the runoff ratio and EI30 was developed from the concept that soil loss is the product of runoff and sediment concentration and operates in a way that obeys the mathematical rules upon which the USLE/RUSLE model was based. In accounts for event soil loss better that the EI30 index where runoff values are known or predicted adequately. RUSLE2 now includes a capacity to model runoff driven erosion.

Seventeen years of statin pharmacogenetics: a systematic review.

PubMed

Leusink, Maarten; Onland-Moret, N Charlotte; de Bakker, Paul I W; de Boer, Anthonius; Maitland-van der Zee, Anke H

2016-01-01

We evaluated the evidence of pharmacogenetic associations with statins in a systematic review. Two separate outcomes were considered of interest: modification of low-density lipoprotein cholesterol (LDL-C) response and modification of risk for cardiovascular events. In candidate gene studies, 141 loci were claimed to be associated with LDL-C response. Only 5% of these associations were positively replicated. In addition, six genome-wide association studies of LDL-C response identified common SNPs in APOE, LPA, SLCO1B1, SORT1 and ABCG2 at genome-wide significance. None of the investigated SNPs consistently affected the risk reduction for cardiovascular events. Only five genetic loci were consistently associated with LDL-C response. However, as effect sizes are modest, there is no evidence for the value of genetic testing in clinical practice.

Statistical Analysis of Solar Events Associated with Storm Sudden Commencements over One Year of Solar Maximum during Cycle 23: Propagation and Effects from the Sun to the Earth.

NASA Astrophysics Data System (ADS)

Bocchialini, K.; Grison, B.; Menvielle, M.; Chambodut, A.; Cornilleau-Wehrlin, N.; Fontaine, D.; Marchaudon, A.; Pick, M.; Pitout, F.; Schmieder, B.; Régnier, S.; Zouganelis, I.

2017-12-01

From the list of 32 SSCs over the year 2002, we performed a multi-criteria analysis based on propagation time, velocity comparison, sense of the magnetic field rotation, radio waves to associate them with solar sources, identify their causes in the interplanetary medium and then look at the response of the terrestrial ionized and neutral environment to them. The complex interactions between two (or more) CMEs and the modification in their trajectory have been examined using joint white light and multiple-wavelength radio observations. The structures at L_1 after the 32 SSCs are regarded as Magnetic Clouds (MCs), ICMEs without a MC structure, Miscellaneous structures, CIRs/SIRs, and shock-only events. In terms of geoeffectivity, generally CMEs with velocities at the Sun larger than 1000 km.s-1 have larger probabilities to trigger moderate or intense storms. The most geoeffective events are MCs, since 92% of them trigger moderate or intense storms. The geoeffective events trigger an increased and combined AKR and NTC wave activity in the magnetosphere, an enhanced convection in the ionosphere and a stronger response in the thermosphere.

The WSMR Timing System: Toward New Horizons

NASA Technical Reports Server (NTRS)

Gilbert, William A.; Stimets, Bob

1996-01-01

In 1991, White Sands Missile Range (WSMR) initiated a modernization program for its range timing system. The main focus of this modernization program was to develop a system that was highly accurate, easy to maintain, and portable. The logical decision at the time was to develop a system based solely on Global Positioning System (GPS) technology. Since that time, wsmr has changed its philosophy on how GPS would be utilized for the timing system. This paper will describe WSMR's initial modernization plans for its range timing system and how certain events have led to a modification of these plans.

In What Ways Do Synthetic Nucleotides and Natural Base Lesions Alter the Structural Stability of G-Quadruplex Nucleic Acids?

PubMed Central

2017-01-01

Synthetic analogs of natural nucleotides have long been utilized for structural studies of canonical and noncanonical nucleic acids, including the extensively investigated polymorphic G-quadruplexes (GQs). Dependence on the sequence and nucleotide modifications of the folding landscape of GQs has been reviewed by several recent studies. Here, an overview is compiled on the thermodynamic stability of the modified GQ folds and on how the stereochemical preferences of more than 70 synthetic and natural derivatives of nucleotides substituting for natural ones determine the stability as well as the conformation. Groups of nucleotide analogs only stabilize or only destabilize the GQ, while the majority of analogs alter the GQ stability in both ways. This depends on the preferred syn or anti N-glycosidic linkage of the modified building blocks, the position of substitution, and the folding architecture of the native GQ. Natural base lesions and epigenetic modifications of GQs explored so far also stabilize or destabilize the GQ assemblies. Learning the effect of synthetic nucleotide analogs on the stability of GQs can assist in engineering a required stable GQ topology, and exploring the in vitro action of the single and clustered natural base damage on GQ architectures may provide indications for the cellular events. PMID:29181193

Transport and solubility of Hetero-disperse dry deposition particulate matter subject to urban source area rainfall-runoff processes

NASA Astrophysics Data System (ADS)

Ying, G.; Sansalone, J.

2010-03-01

SummaryWith respect to hydrologic processes, the impervious pavement interface significantly alters relationships between rainfall and runoff. Commensurate with alteration of hydrologic processes the pavement also facilitates transport and solubility of dry deposition particulate matter (PM) in runoff. This study examines dry depositional flux rates, granulometric modification by runoff transport, as well as generation of total dissolved solids (TDS), alkalinity and conductivity in source area runoff resulting from PM solubility. PM is collected from a paved source area transportation corridor (I-10) in Baton Rouge, Louisiana encompassing 17 dry deposition and 8 runoff events. The mass-based granulometric particle size distribution (PSD) is measured and modeled through a cumulative gamma function, while PM surface area distributions across the PSD follow a log-normal distribution. Dry deposition flux rates are modeled as separate first-order exponential functions of previous dry hours (PDH) for PM and suspended, settleable and sediment fractions. When trans-located from dry deposition into runoff, PSDs are modified, with a d50m decreasing from 331 to 14 μm after transport and 60 min of settling. Solubility experiments as a function of pH, contact time and particle size using source area rainfall generate constitutive models to reproduce pH, alkalinity, TDS and alkalinity for historical events. Equilibrium pH, alkalinity and TDS are strongly influenced by particle size and contact times. The constitutive leaching models are combined with measured PSDs from a series of rainfall-runoff events to demonstrate that the model results replicate alkalinity and TDS in runoff from the subject watershed. Results illustrate the granulometry of dry deposition PM, modification of PSDs along the drainage pathway, and the role of PM solubility for generation of TDS, alkalinity and conductivity in urban source area rainfall-runoff.

Surface Modification Enhanced Reflection Intensity of Quartz Crystal Microbalance Sensors upon Molecular Adsorption.

PubMed

Kojima, Taisuke

2018-01-01

Molecular adsorption on a sensing surface involves molecule-substrate and molecule-molecule interactions. Combining optical systems and a quartz crystal microbalance (QCM) on the same sensing surface allows the quantification of such interactions and reveals the physicochemical properties of the adsorbed molecules. However, low sensitivity of the current reflection-based techniques compared to the QCM technique hinders the quantitative analysis of the adsorption events. Here, a layer-by-layer surface modification of a QCM sensor is studied to increase the optical sensitivity. The intermediate layers of organic-inorganic molecules and metal-metal oxide were explored on a gold (Au) surface of a QCM sensor. First, polyhedral oligomeric silsesquioxane-derivatives that served as the organic-inorganic intermediate layer were synthesized and modified on the Au-QCM surface. Meanwhile, titanium oxide, fabricated by anodic oxidation of titanium, was used as a metal-metal oxide intermediate layer on a titanium-coated QCM surface. The developed technique enabled interrogation of the molecular adsorption owing to the enhanced optical sensitivity.

Adaptation to the Local Environment by Modifications of the Photoperiod Response in Crops

PubMed Central

Nakamichi, Norihito

2015-01-01

Flowering plants produce a meristem at the shoot tip where specialized tissue generates shoot apical meristems at the appropriate time to differentiate into reproductive structures, pollinate and efficiently generate seeds. The complex set of molecular and phenological events culminating in development of a flowering meristem is referred to as ‘flowering time’. Flowering time affects plant productivity because plants dedicate energy to produce flowers and seeds rather than vegetative tissue once the molecular decision to initiate flowering has been taken. Thus, initiation of flowering time is an important decision in plants, especially in annual plants including crops. Humans have introduced crops into latitudes and climate areas far from their origin or natural ecosystem, requiring in many cases modification of native flowering times. Recent molecular–genetic studies shed light on the genetic basis related to such introductions. In this review, recent progress regarding crop introductions and their genetic bases are summarized, as well as the potential of other agricultural plants to be introduced into different climatic zones. PMID:25432974

Memory modification as an outcome variable in anxiety disorder treatment.

PubMed

Tryon, Warren W; McKay, Dean

2009-05-01

Learning and memory are interdependent processes. Memories are learned, and cumulative learning requires memory. It is generally accepted that learning contributes to psychopathology and consequently to pertinent memory formation. Neuroscience and psychological research have established that memory is an active reconstructive process that is influenced by thoughts, feelings, and behaviors including post-event information. Recent research on the treatment of anxiety disorders using medications (i.e., d-cyclcloserine) to alter neurological systems associated with memory used in conjunction with behavior therapy suggests that memory is part of a central mechanism in the etiology and maintenance of these conditions. The main thesis of this article is that learning-based interventions create new memories that may modify existing ones. This raises the possibility of using such memory modifications to measure intervention outcome. A connectionist context for understanding this phenomenon and informing intervention is provided, with specific reference to post-traumatic stress disorder, obsessive-compulsive disorder, and generalized anxiety disorder. Recommendations for future research examining the role of memory change in treatment outcome are suggested.

Analytical challenges translating mass spectrometry-based phosphoproteomics from discovery to clinical applications

PubMed Central

Iliuk, Anton B.; Arrington, Justine V.; Tao, Weiguo Andy

2014-01-01

Phosphoproteomics is the systematic study of one of the most common protein modifications in high throughput with the aim of providing detailed information of the control, response, and communication of biological systems in health and disease. Advances in analytical technologies and strategies, in particular the contributions of high-resolution mass spectrometers, efficient enrichments of phosphopeptides, and fast data acquisition and annotation, have catalyzed dramatic expansion of signaling landscapes in multiple systems during the past decade. While phosphoproteomics is an essential inquiry to map high-resolution signaling networks and to find relevant events among the apparently ubiquitous and widespread modifications of proteome, it presents tremendous challenges in separation sciences to translate it from discovery to clinical practice. In this mini-review, we summarize the analytical tools currently utilized for phosphoproteomic analysis (with focus on MS), progresses made on deciphering clinically relevant kinase-substrate networks, MS uses for biomarker discovery and validation, and the potential of phosphoproteomics for disease diagnostics and personalized medicine. PMID:24890697

Impacts of tropical deforestation. Part II: The role of large-scale dynamics

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

Zhang, H.; Henderson-Sellers, A.; McGuffie, K.

1996-10-01

This is the second in a pair of papers in which the possible impacts of tropical deforestation are examined using a version of the NCAR CCM1. The emphasis in this paper is on the influence of tropical deforestation on the large-scale climate system. This influence is explored through the examination of the regional moisture budget and through an analysis of the Hadley and Walker circulations. Modification of the model surface parameters to simulate tropical deforestation produces significant modifications of both Hadley and Walker circulations, which result in changes distant from the region of deforestation. A mechanism for propagation to middlemore » and high latitudes of disturbances arising form tropical deforestation is proposed based on Rossby wave propagation mechanisms. These mechanisms, which have also been associated with the extratropical influences of ENSO events, provide a pathway for the dispersion of the tropical disturbances to high latitudes. 27 refs., 20 figs., 1 tab.« less

Commentary: physical approaches for the treatment of epilepsy: electrical and magnetic stimulation and cooling.

PubMed

Löscher, Wolfgang; Cole, Andrew J; McLean, Michael J

2009-04-01

Physical approaches for the treatment of epilepsy currently under study or development include electrical or magnetic brain stimulators and cooling devices, each of which may be implanted or applied externally. Some devices may stimulate peripheral structures, whereas others may be implanted directly into the brain. Stimulation may be delivered chronically, intermittently, or in response to either manual activation or computer-based detection of events of interest. Physical approaches may therefore ultimately be appropriate for seizure prophylaxis by causing a modification of the underlying substrate, presumably with a reduction in the intrinsic excitability of cerebral structures, or for seizure termination, by interfering with the spontaneous discharge of pathological neuronal networks. Clinical trials of device-based therapies are difficult due to ethical issues surrounding device implantation, problems with blinding, potential carryover effects that may occur in crossover designs if substrate modification occurs, and subject heterogeneity. Unresolved issues in the development of physical treatments include optimization of stimulation parameters, identification of the optimal volume of brain to be stimulated, development of adequate power supplies to stimulate the necessary areas, and a determination that stimulation itself does not promote epileptogenesis or adverse long-term effects on normal brain function.

The anomalous circulation associated with the ENSO-related west Pacific sea surface temperature gradient

USGS Publications Warehouse

Hoell, Andrew; Funk, Christopher C.

2013-01-01

The temporal evolution and distribution of Pacific SST as well as the near-surface tropical Pacific zonal wind, tropical divergence and vertical velocity are considerably different during ENSO events partitioned according to the strength of the WPG. Modifications to the tropical circulation result in changes to the Indo-west Pacific precipitation and vertically integrated energy budgets and are linked to strong and consistent circulation and precipitation modifications throughout the Northern Hemisphere during winter.

Study on Failure of Third-Party Damage for Urban Gas Pipeline Based on Fuzzy Comprehensive Evaluation.

PubMed

Li, Jun; Zhang, Hong; Han, Yinshan; Wang, Baodong

2016-01-01

Focusing on the diversity, complexity and uncertainty of the third-party damage accident, the failure probability of third-party damage to urban gas pipeline was evaluated on the theory of analytic hierarchy process and fuzzy mathematics. The fault tree of third-party damage containing 56 basic events was built by hazard identification of third-party damage. The fuzzy evaluation of basic event probabilities were conducted by the expert judgment method and using membership function of fuzzy set. The determination of the weight of each expert and the modification of the evaluation opinions were accomplished using the improved analytic hierarchy process, and the failure possibility of the third-party to urban gas pipeline was calculated. Taking gas pipelines of a certain large provincial capital city as an example, the risk assessment structure of the method was proved to conform to the actual situation, which provides the basis for the safety risk prevention.

The application of genome-wide 5-hydroxymethylcytosine studies in cancer research.

PubMed

Thomson, John P; Meehan, Richard R

2017-01-01

Early detection and characterization of molecular events associated with tumorgenesis remain high priorities. Genome-wide epigenetic assays are promising diagnostic tools, as aberrant epigenetic events are frequent and often cancer specific. The deposition and analysis of multiple patient-derived cancer epigenomic profiles contributes to our appreciation of the underlying biology; aiding the detection of novel identifiers for cancer subtypes. Modifying enzymes and co-factors regulating these epigenetic marks are frequently mutated in cancers, and as epigenetic modifications themselves are reversible, this makes their study very attractive with respect to pharmaceutical intervention. Here we focus on the novel modified base, 5-hydoxymethylcytosine, and discuss how genome-wide 5-hydoxymethylcytosine profiling expedites our molecular understanding of cancer, serves as a lineage tracer, classifies the mode of action of potentially carcinogenic agents and clarifies the roles of potential novel cancer drug targets; thus assisting the development of new diagnostic/prognostic tools.

Identification of the functional groups on the surface of nanoparticles formed in photonucleation of aldehydes generated during forest fire events

NASA Astrophysics Data System (ADS)

Dultsev, Fedor N.; Mik, Ivan A.; Dubtsov, Sergei N.; Dultseva, Galina G.

2014-11-01

We describe the new procedure developed to determine the functional groups on the surface of nanoparticles formed in photonucleation of furfural, one of the aldehydes generated during forest fire events. The procedure is based on the detection of nanoparticle rupture from chemically modified surface of the quartz crystal microbalance oscillating in the thickness shear mode under voltage sweep. The rupture force is determined from the voltage at which the rupture occurs. It depends on particle mass and on the affinity of the surface functional groups of the particle to the groups that are present on the modified QCM surface. It was demonstrated with the amine modification of the surface that the nanoparticles formed in furfural photonucleation contain carbonyl and carboxyl groups. The applicability of the method for the investigation of functional groups on the surface of the nanoparticles of atmospheric aerosol is demonstrated.

Exoplanet Science in the National Science Olympiad

NASA Astrophysics Data System (ADS)

Komacek, Thaddeus D.; Young, Donna

2015-11-01

The National Science Olympiad is one of the United States' largest science competitions, reaching over 6,000 schools in 48 states. The Olympiad includes a wide variety of events, stretching a full range of potential future STEM careers, from biological sciences to engineering to earth and space sciences. The Astronomy event has been a mainstay at the high school level for well over a decade, and nominally focuses on aspects of stellar evolution. For the 2014-2015 competition season, the event focus was aligned to include exoplanet discovery and characterization along with star formation. Teams studied both the qualitative features of exoplanets and exoplanetary systems and the quantitative aspects behind their discovery and characterization, including basic calculations with the transit and radial velocity methods. Students were also expected to have a qualitative understanding of stellar evolution and understand the differences between classes of young stars including T Tauri and FU Orionis variables, and Herbig Ae/Be stars. Based on the successes of this event topic, we are continuing this event into the 2015-2016 academic year. The key modification is the selection of new exoplanetary systems for students to research. We welcome feedback from the community on how to improve the event and the related educational resources that are created for Science Olympiad students and coaches. We also encourage any interested community members to contact your regional or state Science Olympiad tournament directors and volunteer to organize competitions and supervise events locally.

Epigenetic Alterations in Cellular Immunity: New Insights into Autoimmune Diseases.

PubMed

Wang, Zijun; Lu, Qianjin; Wang, Zhihui

2017-01-01

Epigenetic modification is an additional regulator in immune responses as the genome-wide profiling somehow fails to explain the sophisticated mechanisms in autoimmune diseases. The effect of epigenetic modifications on adaptive immunity derives from their regulations to induce a permissive or negative gene expression. Epigenetic events, such as DNA methylation, histone modifications and microRNAs (miRNAs) are often found in T cell activation, differentiation and commitment which are the major parts in cellular immunity. Recognizing the complexity of interactions between epigenetic mechanisms and immune disturbance in autoimmune diseases is essential for the exploration of efficient therapeutic targets. In this review, we summarize a list of studies that indicate the significance of dysregulated epigenetic modifications in autoimmune diseases while focusing on T cell immunity. © 2017 The Author(s)Published by S. Karger AG, Basel.

The Howling Prescribed Natural Fire - long-term effects on the modernization of planning and implementation of wildland fire management

Treesearch

Tom Zimmerman; Laurie Kurth; Mitchell Burgard

2011-01-01

Wildland fire management policy and practices have long been driven by the occurrence of significant events. The Howling Prescribed Natural Fire in Glacier National Park in 1994 is a prime example of a significant historical fire event that provided the impetus for program changes and modifications that modernized wildland fire management at the local, regional, and...

Comparison of algorithms to generate event times conditional on time-dependent covariates.

PubMed

Sylvestre, Marie-Pierre; Abrahamowicz, Michal

2008-06-30

The Cox proportional hazards model with time-dependent covariates (TDC) is now a part of the standard statistical analysis toolbox in medical research. As new methods involving more complex modeling of time-dependent variables are developed, simulations could often be used to systematically assess the performance of these models. Yet, generating event times conditional on TDC requires well-designed and efficient algorithms. We compare two classes of such algorithms: permutational algorithms (PAs) and algorithms based on a binomial model. We also propose a modification of the PA to incorporate a rejection sampler. We performed a simulation study to assess the accuracy, stability, and speed of these algorithms in several scenarios. Both classes of algorithms generated data sets that, once analyzed, provided virtually unbiased estimates with comparable variances. In terms of computational efficiency, the PA with the rejection sampler reduced the time necessary to generate data by more than 50 per cent relative to alternative methods. The PAs also allowed more flexibility in the specification of the marginal distributions of event times and required less calibration.

Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

PubMed

Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

2012-11-01

Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Secondary stroke prevention: from guidelines to clinical practice.

PubMed

Graham, Glenn D

2008-10-01

Stroke remains a leading cause of mortality and is associated with substantial morbidity in the United States. The majority of strokes are of ischemic origin, with an atherothrombotic trigger, and the clinical manifestation of atherothrombosis depends on the affected vascular site. The systemic nature of atherosclerosis means that stroke patients are at increased risk of ischemic events in several vascular beds, including cerebral, coronary and peripheral sites. Because stroke patients are at heightened risk of more ischemic events, secondary prevention is an important therapeutic goal. Recently, the American Heart Association and its division, the American Stroke Association, released new evidence-based guidelines for secondary stroke prevention in patients with ischemic stroke or transient ischemic attack. The new guidelines emphasize an individualized, patient-oriented approach to treatment based on clinical evidence. Evidence-based recommendations are set forth for the management of risk factors, including hypertension, dyslipidemia and diabetes, through lifestyle modifications and pharmacological interventions. The purpose of this paper is to review the topic of stroke prevention in light of current guidelines and clinical implementation patterns for primary care physicians, and to discuss new and emerging clinical evidence, with a focus on antiplatelet treatment.

Safety Modification of Cam-and-Groove Hose Coupling

NASA Technical Reports Server (NTRS)

Schwindt, Paul; Littlefield, Alan

2008-01-01

A modification has been made in the mating halves of a cam-and-groove hose coupling to prevent rapid separation of the halves in the event that the cam levers are released while the fluid in the hose is pressurized. The need for this modification arises because commercial off-the-shelf cam-and-groove hose-coupling halves do not incorporate safety features to prevent separation in the pressurized state. Especially when the pressurized fluid is compressible (e.g., steam or compressed air), the separated halves can be propelled with considerable energy, causing personal injury and/or property damage. Therefore, one purpose served by the modification is to provide for venting to release compressive energy in a contained and safe manner while preventing personal injury and/or property damage. Another purpose served by the modification, during the process of connecting the coupling halves, is to ensure that the coupling halves are properly aligned before the cam levers can be locked into position.

Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1

PubMed Central

Chang, Chuang-Rung; Blackstone, Craig

2017-01-01

Mitochondria in cells comprise a tubulovesicular network shaped continuously by complementary fission and fusion events. The mammalian Drp1 protein plays a key role in fission, while Mfn1, Mfn2, and OPA1 are required for fusion. Shifts in the balance between these opposing processes can occur rapidly, indicating that modifications to these proteins may regulate mitochondrial membrane dynamics. We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized. This dynamin-related GTPase undergoes a number of steps to mediate mitochondrial fission, including translocation from cytoplasm to the mitochondrial outer membrane, higher-order assembly into spirals, GTP hydrolysis associated with a conformational change and membrane deformation, and ultimately disassembly. Many of these steps may be influenced by covalent modification of Drp1. We discuss the dynamic nature of Drp1 modifications and how they contribute not only to the normal regulation of mitochondrial division, but also to neuropathologic processes. PMID:20649536

Genome-wide identification of sweet orange (Citrus sinensis) histone modification gene families and their expression analysis during the fruit development and fruit-blue mold infection process

PubMed Central

Xu, Jidi; Xu, Haidan; Liu, Yuanlong; Wang, Xia; Xu, Qiang; Deng, Xiuxin

2015-01-01

In eukaryotes, histone acetylation and methylation have been known to be involved in regulating diverse developmental processes and plant defense. These histone modification events are controlled by a series of histone modification gene families. To date, there is no study regarding genome-wide characterization of histone modification related genes in citrus species. Based on the two recent sequenced sweet orange genome databases, a total of 136 CsHMs (Citrus sinensis histone modification genes), including 47 CsHMTs (histone methyltransferase genes), 23 CsHDMs (histone demethylase genes), 50 CsHATs (histone acetyltransferase genes), and 16 CsHDACs (histone deacetylase genes) were identified. These genes were categorized to 11 gene families. A comprehensive analysis of these 11 gene families was performed with chromosome locations, phylogenetic comparison, gene structures, and conserved domain compositions of proteins. In order to gain an insight into the potential roles of these genes in citrus fruit development, 42 CsHMs with high mRNA abundance in fruit tissues were selected to further analyze their expression profiles at six stages of fruit development. Interestingly, a numbers of genes were expressed highly in flesh of ripening fruit and some of them showed the increasing expression levels along with the fruit development. Furthermore, we analyzed the expression patterns of all 136 CsHMs response to the infection of blue mold (Penicillium digitatum), which is the most devastating pathogen in citrus post-harvest process. The results indicated that 20 of them showed the strong alterations of their expression levels during the fruit-pathogen infection. In conclusion, this study presents a comprehensive analysis of the histone modification gene families in sweet orange and further elucidates their behaviors during the fruit development and the blue mold infection responses. PMID:26300904

Chiral reagents in glycosylation and modification of carbohydrates.

PubMed

Wang, Hao-Yuan; Blaszczyk, Stephanie A; Xiao, Guozhi; Tang, Weiping

2018-02-05

Carbohydrates play a significant role in numerous biological events, and the chemical synthesis of carbohydrates is vital for further studies to understand their various biological functions. Due to the structural complexity of carbohydrates, the stereoselective formation of glycosidic linkages and the site-selective modification of hydroxyl groups are very challenging and at the same time extremely important. In recent years, the rapid development of chiral reagents including both chiral auxiliaries and chiral catalysts has significantly improved the stereoselectivity for glycosylation reactions and the site-selectivity for the modification of carbohydrates. These new tools will greatly facilitate the efficient synthesis of oligosaccharides, polysaccharides, and glycoconjugates. In this tutorial review, we will summarize these advances and highlight the most recent examples.

Chemical Posttranslational Modification with Designed Rhodium(II) Catalysts.

PubMed

Martin, S C; Minus, M B; Ball, Z T

2016-01-01

Natural enzymes use molecular recognition to perform exquisitely selective transformations on nucleic acids, proteins, and natural products. Rhodium(II) catalysts mimic this selectivity, using molecular recognition to allow selective modification of proteins with a variety of functionalized diazo reagents. The rhodium catalysts and the diazo reactivity have been successfully applied to a variety of protein folds, the chemistry succeeds in complex environments such as cell lysate, and a simple protein blot method accurately assesses modification efficiency. The studies with rhodium catalysts provide a new tool to study and probe protein-binding events, as well as a new synthetic approach to protein conjugates for medical, biochemical, or materials applications. © 2016 Elsevier Inc. All rights reserved.

Engineered Aptamers to Probe Molecular Interactions on the Cell Surface

PubMed Central

Batool, Sana; Bhandari, Sanam; George, Shanell; Okeoma, Precious; Van, Nabeela; Zümrüt, Hazan E.; Mallikaratchy, Prabodhika

2017-01-01

Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in vitro evolution method enabling the design and development of aptamer-based functional molecular scaffolds against wide range of cell surface molecules. This article reviews the application of aptamers as monitors and modulators of molecular interactions on the mammalian cell surface with the aim of increasing our understanding of cell-surface receptor response to external stimuli. The information gained from these types of studies could eventually prove useful in engineering improved medical diagnostics and therapeutics. PMID:28850067

A method for modeling bias in a person's estimates of likelihoods of events

NASA Technical Reports Server (NTRS)

Nygren, Thomas E.; Morera, Osvaldo

1988-01-01

It is of practical importance in decision situations involving risk to train individuals to transform uncertainties into subjective probability estimates that are both accurate and unbiased. We have found that in decision situations involving risk, people often introduce subjective bias in their estimation of the likelihoods of events depending on whether the possible outcomes are perceived as being good or bad. Until now, however, the successful measurement of individual differences in the magnitude of such biases has not been attempted. In this paper we illustrate a modification of a procedure originally outlined by Davidson, Suppes, and Siegel (3) to allow for a quantitatively-based methodology for simultaneously estimating an individual's subjective utility and subjective probability functions. The procedure is now an interactive computer-based algorithm, DSS, that allows for the measurement of biases in probability estimation by obtaining independent measures of two subjective probability functions (S+ and S-) for winning (i.e., good outcomes) and for losing (i.e., bad outcomes) respectively for each individual, and for different experimental conditions within individuals. The algorithm and some recent empirical data are described.

Positive interventions: An emotion regulation perspective.

PubMed

Quoidbach, Jordi; Mikolajczak, Moïra; Gross, James J

2015-05-01

The rapid growth of the literature on positive interventions to increase "happiness" has suggested the need for an overarching conceptual framework to integrate the many and apparently disparate findings. In this review, we used the process model of emotion regulation (Gross, 1998) to organize the existing literature on positive interventions and to advance theory by clarifying the mechanisms underlying their effectiveness. We have proposed that positive emotions can be increased both in the short- and longer-term through 5 families of emotion regulation strategies (i.e., situation selection, situation modification, attentional deployment, cognitive change, and response modulation), showing how these emotion regulation strategies can be applied before, during, and after positive emotional events. Regarding short-term increases in positive emotions, our review found that attentional deployment, cognitive change, and response modulation strategies have received the most empirical support, whereas more work is needed to establish the effectiveness of situation selection and situation modification strategies. Regarding longer-term increases in positive emotions, strategies such as situation selection during an event and attentional deployment before, during, and after an event have received strong empirical support and are at the center of many positive interventions. However, more work is needed to establish the specific benefits of the other strategies, especially situation modification. We argue that our emotion regulation framework clarifies existing interventions and points the way for new interventions that might be used to increase positive emotions in both nonclinical and clinical populations. (c) 2015 APA, all rights reserved).

The safety of pharmacologic treatment for pediatric obesity.

PubMed

Chao, Ariana M; Wadden, Thomas A; Berkowitz, Robert I

2018-04-01

Pediatric obesity is a serious public health concern. Five medications have been approved by the Food and Drug Administration (FDA) for chronic weight management in adults with obesity, when used as an adjunct to lifestyle modification. Orlistat is the only FDA-approved medication for pediatric patients aged 12 years and above. Areas covered: This paper summarizes safety and efficacy data from clinical trials of weight loss medications conducted among pediatric samples. Relevant studies were identified through searches in PubMed. Expert opinion: Orlistat, as an adjunct to lifestyle modification, results in modest weight losses and may be beneficial for some pediatric patients with obesity. However, gastrointestinal side effects are common and may limit use. In adults taking orlistat, rare but severe adverse events, including liver and renal events, have been reported. Recent pediatric pharmacokinetic studies of liraglutide have demonstrated similar safety and tolerability profiles as found in adults, with gastrointestinal disorders being the most common adverse events. Clinical trials are needed of liraglutide, as well as other medications for obesity, that systematically evaluate their risks and benefits in pediatric patients.

Early Exposure to Traffic-Related Air Pollution, Respiratory Symptoms at 4 Years of Age, and Potential Effect Modification by Parental Allergy, Stressful Family Events, and Sex: A Prospective Follow-up Study of the PARIS Birth Cohort

PubMed Central

Rancière, Fanny; Bougas, Nicolas; Viola, Malika; Momas, Isabelle

2016-01-01

Background: The relation between traffic-related air pollution (TRAP) exposure and the incidence of asthma/allergy in preschool children has been widely studied, but results remain heterogeneous, possibly due to differences in methodology and susceptibility to TRAP. Objectives: We aimed to study the relation of early TRAP exposure with the development of respiratory/allergic symptoms and asthma during preschool years, and to investigate parental allergy, “stressful” family events, and sex as possible effect modifiers. Methods: We examined data of 2,015 children from the PARIS birth cohort followed up with repeated questionnaires completed by parents until age 4 years. TRAP exposure in each child’s first year of life was estimated by nitrogen oxides (NOx) air dispersion modeling, taking into account both home and day care locations. Association between TRAP exposure and patterns of wheezing, dry night cough, and rhinitis symptoms was studied using multinomial logistic regression models adjusted for potential confounders. Effect modification by parental history of allergy, stressful family events, and sex was investigated. Results: An interquartile range (26 μg/m3) increase in NOx levels was associated with an increased odds ratio (OR) of persistent wheezing at 4 years (adjusted OR = 1.27; 95% confidence interval: 1.09, 1.47). TRAP exposure was positively associated with persistent wheeze, dry cough, and rhinitis symptoms among children with a parental allergy, those experiencing stressful family events, and boys, but not in children whose parents did not have allergies or experience stressful events, or in girls (all interaction p-values < 0.2). Conclusions: This study supports the hypothesis that not all preschool children are equal regarding TRAP health effects. Parental history of allergy, stressful family events, and male sex may increase their susceptibility to adverse respiratory effects of early TRAP exposure. Citation: Rancière F, Bougas N, Viola M, Momas I. 2017. Early exposure to traffic-related air pollution, respiratory symptoms at 4 years of age, and potential effect modification by parental allergy, stressful family events, and sex: a prospective follow-up study of the PARIS birth cohort. Environ Health Perspect 125:737–745; http://dx.doi.org/10.1289/EHP239 PMID:27219743

Damage caused by hydrological extremes in a region of southern Italy: comparison between the period 2002-2012 and the past century

NASA Astrophysics Data System (ADS)

Petrucci, Olga; Pasqua, A. Aurora

2013-04-01

The concept of extreme hydrological event should be seen in a relative way, depending on the region for which it is defined, the parameters and the type of data utilized to assess it, and mainly taking into account the length of the period basing on which it is assessed. Measured data concerning rainfall and river flow, which allow statistical analysis of numerical values and assessment of events frequency, can be available for different periods, according to both the study area and the country; nevertheless, the length of the measurement series rarely exceeds 100 years. Thus, the extrapolation to the future of events trend, frequency, seasonality are based on a relatively short and recent period and even the "magnitude" and the classification of "extreme events" can be biased by the length of the observation period. Thus these characteristics may substantially change if their assessment is based on a wider temporal window. Especially in un-gauged basins and concerning severest events, historical data cannot provide systematically measured parameters but they can supply proxy data which allow enlarging the observation period, permitting a better weighing of both recent and old events. The present research is based on the use of a wide historical database concerning phenomena as floods, flash floods and landslides triggered by extreme meteorological events in Calabria (Southern Italy) since 19th century. This database is made of approximately 11,000 records and it includes data coming from different sources as newspapers, archives of national and regional agencies, scientific and technical reports, on-site surveys reports and information collected by interviewing both people involved and local administrators. The recent uploading of data concerning the effects caused in Calabria by these phenomena during the decade 2002-2012 allowed us to analyse a long and updated historical series of events. The aim is to compare -both in terms triggering rainfall and their effects- events magnitude and frequency characterising the last decade to those observed during past decades, even taking into account the lower data availability characterising older epochs. Using the huge amount of available data, an attempt to individuate the typical damage scenario for the study region is carried out, trying to highlight the trend of modifications affecting these events thorough the study period, in an evolutive perspective that can be useful to forecast tendencies of the hydrological risk on a regional basis.

Oligo/Polynucleotide-Based Gene Modification: Strategies and Therapeutic Potential

PubMed Central

Sargent, R. Geoffrey; Kim, Soya

2011-01-01

Oligonucleotide- and polynucleotide-based gene modification strategies were developed as an alternative to transgene-based and classical gene targeting-based gene therapy approaches for treatment of genetic disorders. Unlike the transgene-based strategies, oligo/polynucleotide gene targeting approaches maintain gene integrity and the relationship between the protein coding and gene-specific regulatory sequences. Oligo/polynucleotide-based gene modification also has several advantages over classical vector-based homologous recombination approaches. These include essentially complete homology to the target sequence and the potential to rapidly engineer patient-specific oligo/polynucleotide gene modification reagents. Several oligo/polynucleotide-based approaches have been shown to successfully mediate sequence-specific modification of genomic DNA in mammalian cells. The strategies involve the use of polynucleotide small DNA fragments, triplex-forming oligonucleotides, and single-stranded oligodeoxynucleotides to mediate homologous exchange. The primary focus of this review will be on the mechanistic aspects of the small fragment homologous replacement, triplex-forming oligonucleotide-mediated, and single-stranded oligodeoxynucleotide-mediated gene modification strategies as it relates to their therapeutic potential. PMID:21417933

Magnetospheric disturbance effects on the Equatorial Ionization Anomaly (EIA) : an overview

NASA Astrophysics Data System (ADS)

Abdu, M. A.; Sobral, J. H. A.; de Paula, E. R.; Batista, I. S.

1992-12-01

The Equatorial lonization Anomaly (EIA) development can undergo drastic modification in the form of an anomalous occurrence at local times outside that of its quiet time development and/or inhibition/enhancement at local times of its normal occurrences. This happens for disturbed electrodynamic conditions of the global ionosphere-thermosphere-magnetosphere system, consequent upon the triggering of a magnetospheric storm event. Direct penetration to equatorial latitudes of the magnetospheric electric fields and the thermospheric disturbances involving winds, electric fields and composition changes produce significant alteration in the EIA morphology and dynamics. Results on statistical behaviour based on accumulated ground-based data sets, and those from recent theoretical modelling efforts and from satellite and ground-based observations, are reviewed. Some outstanding problems of the EIA response to magnetospheric disturbances that deserve attention in the coming years are pointed out.

Plasma membrane order and fluidity are diversely triggered by elicitors of plant defence

PubMed Central

Sandor, Roman; Der, Christophe; Grosjean, Kevin; Anca, Iulia; Noirot, Elodie; Leborgne-Castel, Nathalie; Lochman, Jan; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

2016-01-01

Although plants are exposed to a great number of pathogens, they usually defend themselves by triggering mechanisms able to limit disease development. Alongside signalling events common to most such incompatible interactions, modifications of plasma membrane (PM) physical properties could be new players in the cell transduction cascade. Different pairs of elicitors (cryptogein, oligogalacturonides, and flagellin) and plant cells (tobacco and Arabidopsis) were used to address the issue of possible modifications of plant PM biophysical properties induced by elicitors and their links to other events of the defence signalling cascade. We observed an increase of PM order whatever the elicitor/plant cell pair used, provided that a signalling cascade was induced. Such membrane modification is dependent on the NADPH oxidase-mediated reactive oxygen species production. Moreover, cryptogein, which is the sole elicitor able to trap sterols, is also the only one able to trigger an increase in PM fluidity. The use of cryptogein variants with altered sterol-binding properties confirms the strong correlation between sterol removal from the PM and PM fluidity enhancement. These results propose PM dynamics as a player in early signalling processes triggered by elicitors of plant defence. PMID:27604805

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2012 CFR

2012-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2014 CFR

2014-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

43 CFR 3432.1 - Application.

Code of Federal Regulations, 2013 CFR

2013-10-01

... contiguous to those embraced in a lease. In no event shall the acreage in the application, when combined with the total area added by all modifications made after August 4, 1976, exceed 160 acres or the number of...

7 CFR 930.53 - Modification, suspension, or termination of regulations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE TART CHERRIES GROWN IN THE STATES OF MICHIGAN, NEW YORK, PENNSYLVANIA, OREGON, UTAH, WASHINGTON... of regulations. (a) In the event the Board at any time finds that, by reason of changed conditions...

76 FR 48146 - Endangered Species; File No. 1551

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-08

... Mississippi Canyon 252 oil on sea turtle populations in the northern Gulf of Mexico as part of the post-spill Natural Resources Damage Assessment of the BP Deepwater Horizon event. The modification would be valid...

76 FR 66042 - Endangered Species; File No. 1551

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-25

... from Mississippi Canyon 252 oil on sea turtle populations in the northern Gulf of Mexico as part of the post-spill Natural Resources Damage Assessment of the BP Deepwater Horizon event. The modification is...

GRACE risk score: Sex-based validity of in-hospital mortality prediction in Canadian patients with acute coronary syndrome.

PubMed

Gong, Inna Y; Goodman, Shaun G; Brieger, David; Gale, Chris P; Chew, Derek P; Welsh, Robert C; Huynh, Thao; DeYoung, J Paul; Baer, Carolyn; Gyenes, Gabor T; Udell, Jacob A; Fox, Keith A A; Yan, Andrew T

2017-10-01

Although there are sex differences in management and outcome of acute coronary syndromes (ACS), sex is not a component of Global Registry of Acute Coronary Events (GRACE) risk score (RS) for in-hospital mortality prediction. We sought to determine the prognostic utility of GRACE RS in men and women, and whether its predictive accuracy would be augmented through sex-based modification of its components. Canadian men and women enrolled in GRACE and Canadian Registry of Acute Coronary Events were stratified as ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation ACS (NSTE-ACS). GRACE RS was calculated as per original model. Discrimination and calibration were evaluated using the c-statistic and Hosmer-Lemeshow goodness-of-fit test, respectively. Multivariable logistic regression was undertaken to assess potential interactions of sex with GRACE RS components. For the overall cohort (n=14,422), unadjusted in-hospital mortality rate was higher in women than men (4.5% vs. 3.0%, p<0.001). Overall, GRACE RS c-statistic and goodness-of-fit test p-value were 0.85 (95% CI 0.83-0.87) and 0.11, respectively. While the RS had excellent discrimination for all subgroups (c-statistics >0.80), discrimination was lower for women compared to men with STEMI [0.80 (0.75-0.84) vs. 0.86 (0.82-0.89), respectively, p<0.05]. The goodness-of-fit test showed good calibration for women (p=0.86), but suboptimal for men (p=0.031). No significant interaction was evident between sex and RS components (all p>0.25). The GRACE RS is a valid predictor of in-hospital mortality for both men and women with ACS. The lack of interaction between sex and RS components suggests that sex-based modification is not required. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating the effectiveness of Behavior-Based Safety education methods for commercial vehicle drivers.

PubMed

Wang, Xuesong; Xing, Yilun; Luo, Lian; Yu, Rongjie

2018-08-01

Risky driving behavior is one of the main causes of commercial vehicle related crashes. In order to achieve safer vehicle operation, safety education for drivers is often provided. However, the education programs vary in quality and may not always be successful in reducing crash rates. Behavior-Based Safety (BBS) education is a popular approach found effective by numerous studies, but even this approach varies as to the combination of frequency, mode and content used by different education providers. This study therefore evaluates and compares the effectiveness of BBS education methods. Thirty-five drivers in Shanghai, China, were coached with one of three different BBS education methods for 13 weeks following a 13-week baseline phase with no education. A random-effects negative binomial (NB) model was built and calibrated to investigate the relationship between BBS education and the driver at-fault safety-related event rate. Based on the results of the random-effects NB model, event modification factors (EMF) were calculated to evaluate and compare the effectiveness of the methods. Results show that (1) BBS education was confirmed to be effective in safety-related event reduction; (2) the most effective method among the three applied monthly face-to-face coaching, including feedback with video and statistical data, and training on strategies to avoid driver-specific unsafe behaviors; (3) weekly telephone coaching using statistics and strategies was rated by drivers as the most convenient delivery mode, and was also significantly effective. Copyright © 2018 Elsevier Ltd. All rights reserved.

Physics architecture

NASA Astrophysics Data System (ADS)

Konopleva, Nelly

2017-03-01

Fundamental physical theory axiomatics is closely connected with methods of experimental measurements. The difference between the theories using global and local symmetries is explained. It is shown that symmetry group localization leads not only to the change of the relativity principle, but to the fundamental modification of experimental programs testing physical theory predictions. It is noticed that any fundamental physical theory must be consistent with the measurement procedures employed for its testing. These ideas are illustrated by events of my biography connected with Yang-Mills theory transformation from an ordinary phenomenological model to a fundamental physical theory based on local symmetry principles like the Einsteinian General Relativity. Baldin position in this situation is demonstrated.

Facilitating ADLs by Caregivers of Persons with Dementia: The C3P Model

PubMed Central

Amella, Elaine J.; Batchelor-Aselage, Melissa B.

2015-01-01

The purpose of this paper is to explicate a change model for caregivers of persons with dementia to assist them in facilitating meals in the home, at community-based programs and in institutional settings. Building on a Social Ecological Model, the C3P Model—Change the Person, Change the People, Change the Place offers a clear method to adapt care strategies to foster independence while providing appropriate support as the person with dementia cognitively and functionally declines. Meals are highly embedded within a culture and are ritualized events within a family requiring an individualized approach when modifications are needed. PMID:24354332

Audience-Contingent Variation in Action Demonstrations for Humans and Computers

ERIC Educational Resources Information Center

Herberg, Jonathan S.; Saylor, Megan M.; Ratanaswasd, Palis; Levin, Daniel T.; Wilkes, D. Mitchell

2008-01-01

People may exhibit two kinds of modifications when demonstrating action for others: modifications to facilitate bottom-up, or sensory-based processing; and modifications to facilitate top-down, or knowledge-based processing. The current study examined actors' production of such modifications in action demonstrations for audiences that differed in…

Spatiotemporal brain dynamics underlying attentional bias modifications.

PubMed

Sallard, Etienne; Hartmann, Lea; Ptak, Radek; Spierer, Lucas

2018-06-05

Exaggerated attentional biases toward specific elements of the environment contribute to the maintenance of several psychiatric conditions, such as biases to threatening faces in social anxiety. Although recent literature indicates that attentional bias modification may constitute an effective approach for psychiatric remediation, the underlying neurophysiological mechanisms remain unclear. We addressed this question by recording EEG in 24 healthy participants performing a modified dot-probe task in which pairs of neutral cues (colored shapes) were replaced by probe stimuli requiring a discrimination judgment. To induce an attentional bias toward or away from the cues, the probes were systematically presented either at the same or at the opposite position of a specific cue color. This paradigm enabled participants to spontaneously develop biases to initially unbiased, neutral cues, as measured by the response speed to the probe presented after the cues. Behavioral result indicated that the ABM procedure induced approach and avoidance biases. The influence of ABM on inhibitory control was assessed in a separated Go/NoGo task: Changes in AB did not influence participants' capacity to inhibit their responses to the cues. Attentional bias modification was associated with a topographic modulation of event-related potentials already 50-84 ms following the onset of the cues. Statistical analyses of distributed electrical source estimations revealed that the development of attentional biases was associated with decreased activity in the left temporo-parieto-occipital junction. These findings suggest that attentional bias modification affects early sensory processing phases related to the extraction of information based on stimulus saliency. Copyright © 2017. Published by Elsevier B.V.

The Search for Muon Neutrinos from Northern Hemisphere Gamma-Ray Bursts with AMANDA

NASA Astrophysics Data System (ADS)

Achterberg, A.; Ackermann, M.; Adams, J.; Ahrens, J.; Andeen, K.; Auffenberg, J.; Bahcall, J. N.; Bai, X.; Baret, B.; Barwick, S. W.; Bay, R.; Beattie, K.; Becka, T.; Becker, J. K.; Becker, K.-H.; Berghaus, P.; Berley, D.; Bernardini, E.; Bertrand, D.; Besson, D. Z.; Blaufuss, E.; Boersma, D. J.; Bohm, C.; Bolmont, J.; Böser, S.; Botner, O.; Bouchta, A.; Braun, J.; Burgess, C.; Burgess, T.; Castermans, T.; Chirkin, D.; Christy, B.; Clem, J.; Cowen, D. F.; D'Agostino, M. V.; Davour, A.; Day, C. T.; De Clercq, C.; Demirörs, L.; Descamps, F.; Desiati, P.; DeYoung, T.; Diaz-Velez, J. C.; Dreyer, J.; Dumm, J. P.; Duvoort, M. R.; Edwards, W. R.; Ehrlich, R.; Eisch, J.; Ellsworth, R. W.; Evenson, P. A.; Fadiran, O.; Fazely, A. R.; Filimonov, K.; Foerster, M. M.; Fox, B. D.; Franckowiak, A.; Gaisser, T. K.; Gallagher, J.; Ganugapati, R.; Geenen, H.; Gerhardt, L.; Goldschmidt, A.; Goodman, J. A.; Gozzini, R.; Griesel, T.; Gross, A.; Grullon, S.; Gunasingha, R. M.; Gurtner, M.; Hallgren, A.; Halzen, F.; Han, K.; Hanson, K.; Hardtke, D.; Hardtke, R.; Hart, J. E.; Hasegawa, Y.; Hauschildt, T.; Hays, D.; Heise, J.; Helbing, K.; Hellwig, M.; Herquet, P.; Hill, G. C.; Hodges, J.; Hoffman, K. D.; Hommez, B.; Hoshina, K.; Hubert, D.; Hughey, B.; Hulth, P. O.; Hülss, J.-P.; Hultqvist, K.; Hundertmark, S.; Inaba, M.; Ishihara, A.; Jacobsen, J.; Japaridze, G. S.; Johansson, H.; Jones, A.; Joseph, J. M.; Kampert, K.-H.; Kappes, A.; Karg, T.; Karle, A.; Kawai, H.; Kelley, J. L.; Kitamura, N.; Klein, S. R.; Klepser, S.; Kohnen, G.; Kolanoski, H.; Köpke, L.; Kowalski, M.; Kowarik, T.; Krasberg, M.; Kuehn, K.; Labare, M.; Landsman, H.; Leich, H.; Leier, D.; Liubarsky, I.; Lundberg, J.; Lünemann, J.; Madsen, J.; Mase, K.; Matis, H. S.; McCauley, T.; McParland, C. P.; Meli, A.; Messarius, T.; Mészáros, P.; Miyamoto, H.; Mokhtarani, A.; Montaruli, T.; Morey, A.; Morse, R.; Movit, S. M.; Münich, K.; Nahnhauer, R.; Nam, J. W.; Niessen, P.; Nygren, D. R.; Ögelman, H.; Olivas, A.; Patton, S.; Peña-Garay, C.; Pérez de los Heros, C.; Piegsa, A.; Pieloth, D.; Pohl, A. C.; Porrata, R.; Pretz, J.; Price, P. B.; Przybylski, G. T.; Rawlins, K.; Razzaque, S.; Resconi, E.; Rhode, W.; Ribordy, M.; Rizzo, A.; Robbins, S.; Roth, P.; Rott, C.; Rutledge, D.; Ryckbosch, D.; Sander, H.-G.; Sarkar, S.; Schlenstedt, S.; Schmidt, T.; Schneider, D.; Seckel, D.; Semburg, B.; Seo, S. H.; Seunarine, S.; Silvestri, A.; Smith, A. J.; Solarz, M.; Song, C.; Sopher, J. E.; Spiczak, G. M.; Spiering, C.; Stamatikos, M.; Stanev, T.; Steffen, P.; Stezelberger, T.; Stokstad, R. G.; Stoufer, M. C.; Stoyanov, S.; Strahler, E. A.; Straszheim, T.; Sulanke, K.-H.; Sullivan, G. W.; Sumner, T. J.; Taboada, I.; Tarasova, O.; Tepe, A.; Thollander, L.; Tilav, S.; Tluczykont, M.; Toale, P. A.; Turčan, D.; van Eijndhoven, N.; Vandenbroucke, J.; Van Overloop, A.; Viscomi, V.; Voigt, B.; Wagner, W.; Walck, C.; Waldmann, H.; Walter, M.; Wang, Y.-R.; Wendt, C.; Wiebusch, C. H.; Wikström, G.; Williams, D. R.; Wischnewski, R.; Wissing, H.; Woschnagg, K.; Xu, X. W.; Yodh, G.; Yoshida, S.; Zornoza, J. D.; Interplanetary Network, The

2008-02-01

We present the results of the analysis of neutrino observations by the Antarctic Muon and Neutrino Detector Array (AMANDA) correlated with photon observations of more than 400 gamma-ray bursts (GRBs) in the northern hemisphere from 1997 to 2003. During this time period, AMANDA's effective collection area for muon neutrinos was larger than that of any other existing detector. After the application of various selection criteria to our data, we expect ~1 neutrino event and <2 background events. Based on our observations of zero events during and immediately prior to the GRBs in the data set, we set the most stringent upper limit on muon neutrino emission correlated with GRBs. Assuming a Waxman-Bahcall spectrum and incorporating all systematic uncertainties, our flux upper limit has a normalization at 1 PeV of E2Φν <= 6.3 × 10-9 GeV cm-2 s-1 sr-1, with 90% of the events expected within the energy range of ~10 TeV to ~3 PeV. The impact of this limit on several theoretical models of GRBs is discussed, as well as the future potential for detection of GRBs by next-generation neutrino telescopes. Finally, we briefly describe several modifications to this analysis in order to apply it to other types of transient point sources.

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy

PubMed Central

Barhoumi, Aoune; Halas, Naomi J.

2013-01-01

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics. PMID:24427449

Detecting Chemically Modified DNA Bases Using Surface Enhanced Raman Spectroscopy.

PubMed

Barhoumi, Aoune; Halas, Naomi J

2011-12-15

Post-translational modifications of DNA- changes in the chemical structure of individual bases that occur without changes in the DNA sequence- are known to alter gene expression. They are believed to result in frequently deleterious phenotypic changes, such as cancer. Methylation of adenine, methylation and hydroxymethylation of cytosine, and guanine oxidation are the primary DNA base modifications identified to date. Here we show it is possible to use surface enhanced Raman spectroscopy (SERS) to detect these primary DNA base modifications. SERS detection of modified DNA bases is label-free and requires minimal additional sample preparation, reducing the possibility of additional chemical modifications induced prior to measurement. This approach shows the feasibility of DNA base modification assessment as a potentially routine analysis that may be further developed for clinical diagnostics.

40 CFR 267.112 - What procedures must I follow?

Code of Federal Regulations, 2011 CFR

2011-07-01

.... (1) Events leading to a change in the closure plan, and therefore requiring a modification, may include: (i) A change in the operating plan or facility design; (ii) A change in the expected year of...

Computing in the presence of soft bit errors. [caused by single event upset on spacecraft

NASA Technical Reports Server (NTRS)

Rasmussen, R. D.

1984-01-01

It is shown that single-event-upsets (SEUs) due to cosmic rays are a significant source of single bit error in spacecraft computers. The physical mechanism of SEU, electron hole generation by means of Linear Energy Transfer (LET), it discussed with reference made to the results of a study of the environmental effects on computer systems of the Galileo spacecraft. Techniques for making software more tolerant of cosmic ray effects are considered, including: reducing the number of registers used by the software; continuity testing of variables; redundant execution of major procedures for error detection; and encoding state variables to detect single-bit changes. Attention is also given to design modifications which may reduce the cosmic ray exposure of on-board hardware. These modifications include: shielding components operating in LEO; removing low-power Schottky parts; and the use of CMOS diodes. The SEU parameters of different electronic components are listed in a table.

Apparent and internal validity of a Monte Carlo-Markov model for cardiovascular disease in a cohort follow-up study.

PubMed

Nijhuis, Rogier L; Stijnen, Theo; Peeters, Anna; Witteman, Jacqueline C M; Hofman, Albert; Hunink, M G Myriam

2006-01-01

To determine the apparent and internal validity of the Rotterdam Ischemic heart disease & Stroke Computer (RISC) model, a Monte Carlo-Markov model, designed to evaluate the impact of cardiovascular disease (CVD) risk factors and their modification on life expectancy (LE) and cardiovascular disease-free LE (DFLE) in a general population (hereinafter, these will be referred to together as (DF)LE). The model is based on data from the Rotterdam Study, a cohort follow-up study of 6871 subjects aged 55 years and older who visited the research center for risk factor assessment at baseline (1990-1993) and completed a follow-up visit 7 years later (original cohort). The transition probabilities and risk factor trends used in the RISC model were based on data from 3501 subjects (the study cohort). To validate the RISC model, the number of simulated CVD events during 7 years' follow-up were compared with the observed number of events in the study cohort and the original cohort, respectively, and simulated (DF)LEs were compared with the (DF)LEs calculated from multistate life tables. Both in the study cohort and in the original cohort, the simulated distribution of CVD events was consistent with the observed number of events (CVD deaths: 7.1% v. 6.6% and 7.4% v. 7.6%, respectively; non-CVD deaths: 11.2% v. 11.5% and 12.9% v. 13.0%, respectively). The distribution of (DF)LEs estimated with the RISC model consistently encompassed the (DF)LEs calculated with multistate life tables. The simulated events and (DF)LE estimates from the RISC model are consistent with observed data from a cohort follow-up study.

Multiplexed data independent acquisition (MSX-DIA) applied by high resolution mass spectrometry improves quantification quality for the analysis of histone peptides

PubMed Central

Sidoli, Simone; Fujiwara, Rina; Garcia, Benjamin A.

2016-01-01

We present the mass spectrometry (MS) based application of the innovative, although scarcely exploited, multiplexed data-independent acquisition (MSX-DIA) for the analysis of histone post-translational modifications (PTMs). Histones are golden standard for complexity in MS based proteomics, due to their large number of combinatorial modifications, leading to isobaric peptides after proteolytic digestion. DIA has thus gained popularity for the purpose as it allows for MS/MS-based quantification without upfront assay development. In this work, we evaluated the performance of traditional DIA versus MSX-DIA in terms of MS/MS spectra quality, instrument scan rate and quantification precision using histones from HeLa cells. We used an MS/MS isolation window of 10 and 6 m/z for DIA and MSX-DIA, respectively. Four MS/MS scans were multiplexed for MSX-DIA. Despite MSX-DIA was programmed to perform 2-fold more MS/MS events than traditional DIA, it acquired on average ~5% more full MS scans, indicating even faster scan rate. Results highlighted an overall decrease of background ion signals using MSX-DIA, and we illustrated specific examples where peptides of different precursor masses were co-fragmented by DIA but not MSX-DIA. Taken together, MSX-DIA proved thus to be a more favorable method for histone analysis in data independent mode. PMID:27193262

Human vulnerability to stress depends on amygdala's predisposition and hippocampal plasticity

PubMed Central

Admon, Roee; Lubin, Gad; Stern, Orit; Rosenberg, Keren; Sela, Lee; Ben-Ami, Haim; Hendler, Talma

2009-01-01

Variations in people's vulnerability to stressful life events may rise from a predated neural sensitivity as well as from differential neural modifications in response to the event. Because the occurrence of a stressful life event cannot be foreseen, characterizing the temporal trajectory of its neural manifestations in humans has been a real challenge. The current prospective study examined the emotional experience and brain responses of 50 a priori healthy new recruits to the Israeli Defense Forces at 2 time points: before they entered their mandatory military service and after their subsequent exposure to stressful events while deployed in combat units. Over time, soldiers reported on increase in stress symptoms that was correlated with greater amygdala and hippocampus responsiveness to stress-related content. However, these closely situated core limbic regions exhibited different temporal trajectories with regard to the stress effect; whereas amygdala's reactivity before stress predicted the increase in stress symptoms, the hippocampal change in activation over time correlated with the increase in such symptoms. Hippocampal plasticity was also reflected by a modification over time of its functional coupling with the ventromedial prefrontal cortex, and this coupling magnitude was again predicted by predated amygdala reactivity. Together, these findings suggest that variations in human's likelihood to develop symptomatic phenomena following stressful life events may depend on a balanced interplay between their amygdala's predisposing reactivity and hippocampal posteriori intra- and interregional plasticity. Accordingly, an individually tailored therapeutic approach for trauma survivors should target these 2 neural probes while considering their unique temporal prints. PMID:19666562

Single-event burnout of n-p-n bipolar-junction transistors in hybrid DC/DC converters

NASA Astrophysics Data System (ADS)

Warren, K.; Roth, D.; Kinnison, J.; Pappalardo, R.

2002-12-01

Single-event-induced failure of the Lambda Advanced Analog AMF2805S DC/DC Converter has been traced to burnout of an n-p-n transistor in the MOSFET drive stage. The failures were observed during testing while in inhibit mode only. Modifications to prevent burnout of the drive stage were successfully employed. A discussion of the failure mechanism and consequences for DC/DC converter testing are presented.

MatSeis and the GNEM R&E regional seismic anaylsis tools.

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

Chael, Eric Paul; Hart, Darren M.; Young, Christopher John

2003-08-01

To improve the nuclear event monitoring capability of the U.S., the NNSA Ground-based Nuclear Explosion Monitoring Research & Engineering (GNEM R&E) program has been developing a collection of products known as the Knowledge Base (KB). Though much of the focus for the KB has been on the development of calibration data, we have also developed numerous software tools for various purposes. The Matlab-based MatSeis package and the associated suite of regional seismic analysis tools were developed to aid in the testing and evaluation of some Knowledge Base products for which existing applications were either not available or ill-suited. This presentationmore » will provide brief overviews of MatSeis and each of the tools, emphasizing features added in the last year. MatSeis was begun in 1996 and is now a fairly mature product. It is a highly flexible seismic analysis package that provides interfaces to read data from either flatfiles or an Oracle database. All of the standard seismic analysis tasks are supported (e.g. filtering, 3 component rotation, phase picking, event location, magnitude calculation), as well as a variety of array processing algorithms (beaming, FK, coherency analysis, vespagrams). The simplicity of Matlab coding and the tremendous number of available functions make MatSeis/Matlab an ideal environment for developing new monitoring research tools (see the regional seismic analysis tools below). New MatSeis features include: addition of evid information to events in MatSeis, options to screen picks by author, input and output of origerr information, improved performance in reading flatfiles, improved speed in FK calculations, and significant improvements to Measure Tool (filtering, multiple phase display), Free Plot (filtering, phase display and alignment), Mag Tool (maximum likelihood options), and Infra Tool (improved calculation speed, display of an F statistic stream). Work on the regional seismic analysis tools (CodaMag, EventID, PhaseMatch, and Dendro) began in 1999 and the tools vary in their level of maturity. All rely on MatSeis to provide necessary data (waveforms, arrivals, origins, and travel time curves). CodaMag Tool implements magnitude calculation by scaling to fit the envelope shape of the coda for a selected phase type (Mayeda, 1993; Mayeda and Walter, 1996). New tool features include: calculation of a yield estimate based on the source spectrum, display of a filtered version of the seismogram based on the selected band, and the output of codamag data records for processed events. EventID Tool implements event discrimination using phase ratios of regional arrivals (Hartse et al., 1997; Walter et al., 1999). New features include: bandpass filtering of displayed waveforms, screening of reference events based on SNR, multivariate discriminants, use of libcgi to access correction surfaces, and the output of discrim{_}data records for processed events. PhaseMatch Tool implements match filtering to isolate surface waves (Herrin and Goforth, 1977). New features include: display of the signal's observed dispersion and an option to use a station-based dispersion surface. Dendro Tool implements agglomerative hierarchical clustering using dendrograms to identify similar events based on waveform correlation (Everitt, 1993). New features include: modifications to include arrival information within the tool, and the capability to automatically add/re-pick arrivals based on the picked arrivals for similar events.« less

Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome.

PubMed

Franco, Juan Va; Turk, Tarek; Jung, Jae Hung; Xiao, Yu-Tian; Iakhno, Stanislav; Garrote, Virginia; Vietto, Valeria

2018-01-26

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder in which the two main clinical features are pelvic pain and lower urinary tract symptoms. There are currently many approaches for its management, using both pharmacological and non-pharmacological interventions. The National Institute of Health - Chronic Prostatitis Symptom Index (NIH-CPSI) score is a validated measure commonly used to measure CP/CPPS symptoms. To assess the effects of non-pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was August 2017. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available non-pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence (QoE) according to the GRADE methods. We included 38 unique studies with 3290 men with CP/CPPS across 23 comparisons.1. Acupuncture: (three studies, 204 participants) based on short-term follow-up, acupuncture reduces prostatitis symptoms in an appreciable number of participants compared with sham procedure (mean difference (MD) in total NIH-CPSI score -5.79, 95% confidence interval (CI) -7.32 to -4.26, high QoE). Acupuncture likely results in little to no difference in adverse events (moderate QoE). It probably also decreases prostatitis symptoms compared with standard medical therapy in an appreciable number of participants (MD -6.05, 95% CI -7.87 to -4.24, two studies, 78 participants, moderate QoE).2. Circumcision: (one study, 713 participants) based on short-term follow-up, early circumcision probably decreases prostatitis symptoms slightly (NIH-CPSI score MD -3.00, 95% CI -3.82 to -2.18, moderate QoE) and may not be associated with a greater incidence of adverse events compared with control (a waiting list to be circumcised, low QoE).3. Electromagnetic chair: (two studies, 57 participants) based on short-term follow-up, we are uncertain of the effects of the use of an electromagnetic chair on prostatitis symptoms. It may be associated with a greater incidence of adverse events compared with sham procedure (low to very low QoE).4. Lifestyle modifications: (one study, 100 participants) based on short-term follow-up, lifestyle modifications may be associated with a greater improvement in prostatitis symptoms in an appreciable number of participants compared with control (risk ratio (RR) for improvement in NIH-CPSI scores 3.90, 95% CI 2.20 to 6.92, very low QoE). We found no information regarding adverse events.5. Physical activity: (one study, 85 participants) based on short-term follow-up, a physical activity programme may cause a small reduction in prostatitis symptoms compared with control (NIH-CPSI score MD -2.50, 95% CI -4.69 to -0.31, low QoE). We found no information regarding adverse events.6. Prostatic massage: (two studies, 115 participants) based on short-term follow-up, we are uncertain whether the prostatic massage reduces or increases prostatitis symptoms compared with control (very low QoE). We found no information regarding adverse events.7. Extracorporeal shockwave therapy: (three studies, 157 participants) based on short-term follow-up, extracorporeal shockwave therapy reduces prostatitis symptoms compared with control (NIH-CPSI score MD -6.18, 95% CI -7.46 to -4.89, high QoE). These results may not be sustained at medium-term follow-up (low QoE). This treatment may not be associated with a greater incidence of adverse events (low QoE).8. Transrectal thermotherapy compared to medical therapy: (two studies, 237 participants) based on short-term follow-up, transrectal thermotherapy alone or in combination with medical therapy may decrease prostatitis symptoms slightly when compared with medical therapy alone (NIH-CPSI score MD -2.50, 95% CI -3.82 to -1.18, low QoE). One included study reported that participants may experience transient adverse events.9. Other interventions: there is uncertainty about the effects of other interventions included in this review. We found no information regarding psychological support or prostatic surgery. Some of the interventions can decrease prostatitis symptoms in an appreciable number without a greater incidence of adverse events. The QoE was mostly low. Future clinical trials should include a full report of their methods including adequate masking, consistent assessment of all patient-important outcomes including potential treatment-related adverse events and appropriate sample sizes.

Base modifications affecting RNA polymerase and reverse transcriptase fidelity.

PubMed

Potapov, Vladimir; Fu, Xiaoqing; Dai, Nan; Corrêa, Ivan R; Tanner, Nathan A; Ong, Jennifer L

2018-06-20

Ribonucleic acid (RNA) is capable of hosting a variety of chemically diverse modifications, in both naturally-occurring post-transcriptional modifications and artificial chemical modifications used to expand the functionality of RNA. However, few studies have addressed how base modifications affect RNA polymerase and reverse transcriptase activity and fidelity. Here, we describe the fidelity of RNA synthesis and reverse transcription of modified ribonucleotides using an assay based on Pacific Biosciences Single Molecule Real-Time sequencing. Several modified bases, including methylated (m6A, m5C and m5U), hydroxymethylated (hm5U) and isomeric bases (pseudouridine), were examined. By comparing each modified base to the equivalent unmodified RNA base, we can determine how the modification affected cumulative RNA polymerase and reverse transcriptase fidelity. 5-hydroxymethyluridine and N6-methyladenosine both increased the combined error rate of T7 RNA polymerase and reverse transcriptases, while pseudouridine specifically increased the error rate of RNA synthesis by T7 RNA polymerase. In addition, we examined the frequency, mutational spectrum and sequence context of reverse transcription errors on DNA templates from an analysis of second strand DNA synthesis.

A stochastical event-based continuous time step rainfall generator based on Poisson rectangular pulse and microcanonical random cascade models

NASA Astrophysics Data System (ADS)

Pohle, Ina; Niebisch, Michael; Zha, Tingting; Schümberg, Sabine; Müller, Hannes; Maurer, Thomas; Hinz, Christoph

2017-04-01

Rainfall variability within a storm is of major importance for fast hydrological processes, e.g. surface runoff, erosion and solute dissipation from surface soils. To investigate and simulate the impacts of within-storm variabilities on these processes, long time series of rainfall with high resolution are required. Yet, observed precipitation records of hourly or higher resolution are in most cases available only for a small number of stations and only for a few years. To obtain long time series of alternating rainfall events and interstorm periods while conserving the statistics of observed rainfall events, the Poisson model can be used. Multiplicative microcanonical random cascades have been widely applied to disaggregate rainfall time series from coarse to fine temporal resolution. We present a new coupling approach of the Poisson rectangular pulse model and the multiplicative microcanonical random cascade model that preserves the characteristics of rainfall events as well as inter-storm periods. In the first step, a Poisson rectangular pulse model is applied to generate discrete rainfall events (duration and mean intensity) and inter-storm periods (duration). The rainfall events are subsequently disaggregated to high-resolution time series (user-specified, e.g. 10 min resolution) by a multiplicative microcanonical random cascade model. One of the challenges of coupling these models is to parameterize the cascade model for the event durations generated by the Poisson model. In fact, the cascade model is best suited to downscale rainfall data with constant time step such as daily precipitation data. Without starting from a fixed time step duration (e.g. daily), the disaggregation of events requires some modifications of the multiplicative microcanonical random cascade model proposed by Olsson (1998): Firstly, the parameterization of the cascade model for events of different durations requires continuous functions for the probabilities of the multiplicative weights, which we implemented through sigmoid functions. Secondly, the branching of the first and last box is constrained to preserve the rainfall event durations generated by the Poisson rectangular pulse model. The event-based continuous time step rainfall generator has been developed and tested using 10 min and hourly rainfall data of four stations in North-Eastern Germany. The model performs well in comparison to observed rainfall in terms of event durations and mean event intensities as well as wet spell and dry spell durations. It is currently being tested using data from other stations across Germany and in different climate zones. Furthermore, the rainfall event generator is being applied in modelling approaches aimed at understanding the impact of rainfall variability on hydrological processes. Reference Olsson, J.: Evaluation of a scaling cascade model for temporal rainfall disaggregation, Hydrology and Earth System Sciences, 2, 19.30

Computer simulation techniques for artificial modification of the ionosphere. Final report 31 jan 79-30 apr 81

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

Vance, B.; Mendillo, M.

1981-04-30

A three-dimensional model of the ionosphere was developed including chemical reactions and neutral and plasma transport. The model uses Finite Element Simulation to simulate ionospheric modification rather than solving a set of differential equations. The initial conditions of the Los Alamos Scientific Laboratory experiments, Lagopedo Uno and Dos, were input to the model, and these events were simulated. Simulation results were compared to ground and rocketborne electron-content measurements. A simulation of the transport of released SF6 was also made.

Epigenetic modifications and their relation to caste and sex determination and adult division of labor in the stingless bee Melipona scutellaris

PubMed Central

Cardoso-Júnior, Carlos A.M.; Fujimura, Patrícia Tieme; Santos-Júnior, Célio Dias; Borges, Naiara Araújo; Ueira-Vieira, Carlos; Hartfelder, Klaus; Goulart, Luiz Ricardo; Bonetti, Ana Maria

2017-01-01

Abstract Stingless bees of the genus Melipona, have long been considered an enigmatic case among social insects for their mode of caste determination, where in addition to larval food type and quantity, the genotype also has a saying, as proposed over 50 years ago by Warwick E. Kerr. Several attempts have since tried to test his Mendelian two-loci/two-alleles segregation hypothesis, but only recently a single gene crucial for sex determination in bees was evidenced to be sex-specifically spliced and also caste-specifically expressed in a Melipona species. Since alternative splicing is frequently associated with epigenetic marks, and the epigenetic status plays a major role in setting the caste phenotype in the honey bee, we investigated here epigenetic chromatin modification in the stingless bee Melipona scutellaris. We used an ELISA-based methodology to quantify global methylation status and western blot assays to reveal histone modifications. The results evidenced DNA methylation/demethylation events in larvae and pupae, and significant differences in histone methylation and phosphorylation between newly emerged adult queens and workers. The epigenetic dynamics seen in this stingless bee species represent a new facet in the caste determination process in Melipona bees and suggest a possible mechanism that is likely to link a genotype component to the larval diet and adult social behavior of these bees. PMID:28257527

Epigenetic modifications and their relation to caste and sex determination and adult division of labor in the stingless bee Melipona scutellaris.

PubMed

Cardoso-Júnior, Carlos A M; Fujimura, Patrícia Tieme; Santos-Júnior, Célio Dias; Borges, Naiara Araújo; Ueira-Vieira, Carlos; Hartfelder, Klaus; Goulart, Luiz Ricardo; Bonetti, Ana Maria

2017-01-01

Stingless bees of the genus Melipona, have long been considered an enigmatic case among social insects for their mode of caste determination, where in addition to larval food type and quantity, the genotype also has a saying, as proposed over 50 years ago by Warwick E. Kerr. Several attempts have since tried to test his Mendelian two-loci/two-alleles segregation hypothesis, but only recently a single gene crucial for sex determination in bees was evidenced to be sex-specifically spliced and also caste-specifically expressed in a Melipona species. Since alternative splicing is frequently associated with epigenetic marks, and the epigenetic status plays a major role in setting the caste phenotype in the honey bee, we investigated here epigenetic chromatin modification in the stingless bee Melipona scutellaris. We used an ELISA-based methodology to quantify global methylation status and western blot assays to reveal histone modifications. The results evidenced DNA methylation/demethylation events in larvae and pupae, and significant differences in histone methylation and phosphorylation between newly emerged adult queens and workers. The epigenetic dynamics seen in this stingless bee species represent a new facet in the caste determination process in Melipona bees and suggest a possible mechanism that is likely to link a genotype component to the larval diet and adult social behavior of these bees.

Coupling Poisson rectangular pulse and multiplicative microcanonical random cascade models to generate sub-daily precipitation timeseries

NASA Astrophysics Data System (ADS)

Pohle, Ina; Niebisch, Michael; Müller, Hannes; Schümberg, Sabine; Zha, Tingting; Maurer, Thomas; Hinz, Christoph

2018-07-01

To simulate the impacts of within-storm rainfall variabilities on fast hydrological processes, long precipitation time series with high temporal resolution are required. Due to limited availability of observed data such time series are typically obtained from stochastic models. However, most existing rainfall models are limited in their ability to conserve rainfall event statistics which are relevant for hydrological processes. Poisson rectangular pulse models are widely applied to generate long time series of alternating precipitation events durations and mean intensities as well as interstorm period durations. Multiplicative microcanonical random cascade (MRC) models are used to disaggregate precipitation time series from coarse to fine temporal resolution. To overcome the inconsistencies between the temporal structure of the Poisson rectangular pulse model and the MRC model, we developed a new coupling approach by introducing two modifications to the MRC model. These modifications comprise (a) a modified cascade model ("constrained cascade") which preserves the event durations generated by the Poisson rectangular model by constraining the first and last interval of a precipitation event to contain precipitation and (b) continuous sigmoid functions of the multiplicative weights to consider the scale-dependency in the disaggregation of precipitation events of different durations. The constrained cascade model was evaluated in its ability to disaggregate observed precipitation events in comparison to existing MRC models. For that, we used a 20-year record of hourly precipitation at six stations across Germany. The constrained cascade model showed a pronounced better agreement with the observed data in terms of both the temporal pattern of the precipitation time series (e.g. the dry and wet spell durations and autocorrelations) and event characteristics (e.g. intra-event intermittency and intensity fluctuation within events). The constrained cascade model also slightly outperformed the other MRC models with respect to the intensity-frequency relationship. To assess the performance of the coupled Poisson rectangular pulse and constrained cascade model, precipitation events were stochastically generated by the Poisson rectangular pulse model and then disaggregated by the constrained cascade model. We found that the coupled model performs satisfactorily in terms of the temporal pattern of the precipitation time series, event characteristics and the intensity-frequency relationship.

Progressing from initially ambiguous functional analyses: three case examples.

PubMed

Tiger, Jeffrey H; Fisher, Wayne W; Toussaint, Karen A; Kodak, Tiffany

2009-01-01

Most often functional analyses are initiated using a standard set of test conditions, similar to those described by Iwata, Dorsey, Slifer, Bauman, and Richman [Iwata, B. A., Dorsey, M. F., Slifer, K. J., Bauman, K. E., & Richman, G. S. (1994). Toward a functional analysis of self-injury. Journal of Applied Behavior Analysis, 27, 197-209 (Reprinted from Analysis and Intervention in Developmental Disabilities, 2, 3-20, 1982)]. These test conditions involve the careful manipulation of motivating operations, discriminative stimuli, and reinforcement contingencies to determine the events related to the occurrence and maintenance of problem behavior. Some individuals display problem behavior that is occasioned and reinforced by idiosyncratic or otherwise unique combinations of environmental antecedents and consequences of behavior, which are unlikely to be detected using these standard assessment conditions. For these individuals, modifications to the standard test conditions or the inclusion of novel test conditions may result in clearer assessment outcomes. The current study provides three case examples of individuals whose functional analyses were initially undifferentiated; however, modifications to the standard conditions resulted in the identification of behavioral functions and the implementation of effective function-based treatments.

Comparison Of Intake Gate Closure Methods At Lower Granite, Little Goose, Lower Monumental, And Mcnary Dams Using Risk-Based Analysis

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

Gore, Bryan F.; Blackburn, Tyrone R.; Heasler, Patrick G.

2001-01-19

The objective of this report is to compare the benefits and costs of modifications proposed for intake gate closure systems at four hydroelectric stations on the Lower Snake and Upper Columbia Rivers in the Walla Walla District that are unable to meet the COE 10-minute closure rule due to the installation of fish screens. The primary benefit of the proposed modifications is to reduce the risk of damage to the station and environs when emergency intake gate closure is required. Consequently, this report presents the results and methodology of an extensive risk analysis performed to assess the reliability of powerhousemore » systems and the costs and timing of potential damages resulting from events requiring emergency intake gate closure. As part of this analysis, the level of protection provided by the nitrogen emergency closure system was also evaluated. The nitrogen system was the basis for the original recommendation to partially disable the intake gate systems. The risk analysis quantifies this protection level.« less

Application of a Nanostructured Enzymatic Biosensor Based on Fullerene and Gold Nanoparticles to Polyphenol Detection.

PubMed

Tortolini, Cristina; Sanzò, Gabriella; Antiochia, Riccarda; Mazzei, Franco; Favero, Gabriele

2017-01-01

Electrochemical biosensors provide an attractive means of analyzing the content of a biological sample due to the direct conversion of a biological event to an electronic signal. The signal transduction and the general performance of electrochemical biosensors are often determined by the surface architectures that connect the sensing element to the biological sample at the nanometer scale. The most common surface modification techniques, the various electrochemical transduction mechanisms, and the choice of the recognition receptor molecules all influence the ultimate sensitivity of the sensor. We show herein a novel electrochemical biosensing platform based on the coupling of two different nanostructured materials (gold nanoparticles and fullerenols) displaying interesting electrochemical features. The use of these nanomaterials improved the electrochemical performance of the proposed biosensor.An application of the nanostructured enzyme-based biosensor has been developed for evaluating the detection of polyphenols either in buffer solution or in real wine samples.

Effect of harbor modifications on the tsunami vulnerability of Crescent City, California

NASA Astrophysics Data System (ADS)

Dengler, L.; Uslu, B.

2008-12-01

Crescent City, California has experienced more damaging tsunami events in historic times than any other location on the West Coast of the United States. Thirty-one tsunamis have been observed at Crescent City since a tide gauge was established in 1933, including eleven events with maximum peak to trough wave range exceeding one meter and four that caused damage. The most damaging event occurred in 1964 as a result of the great Alaska earthquake. The ensuing tsunami flooded 29 city blocks and killed 11 in the Crescent City area. As a result of the 1964 tsunami and redevelopment projects, the Crescent City harbor was significantly modified in the early 1970s. A 200 x 300 meter small boat basin was carved into the preexisting shore line, a 123 meter dog leg extension was added to the central breakwater and significant deepening occurred on the eastern side of the harbor. In 2006, a Mw 8.3 earthquake in the Kuril Islands generated a moderate Pacific-wide tsunami. The only location with significant damage was the Crescent City harbor where strong currents damaged docks and boats, causing an estimated 9.2 million (US dollars) in damages. Strong currents estimated by the Harbor Master at 12 knots were observed near the entrance to the small boat basin. Past earthquakes from the northwestern Pacific including the 1933 M 8.3 Sanriku Japan earthquake may have produced similar amplitudes at Crescent City to the 2006 event but caused no damage. We have obtained the pre-modification harbor bathymetry and use the MOST model to compare tsunami water heights and current velocities for the 1933 and 2006 sources using modern and pre- modification bathymetry. We also examine model the 1964 inundation using the actual bathymetry and compare the results to numerical simulations that have only used the modern data.

Synergistic Modification Induced Specific Recognition between Histone and TRIM24 via Fluctuation Correlation Network Analysis

NASA Astrophysics Data System (ADS)

Zhang, Jinmai; Luo, Huajie; Liu, Hao; Ye, Wei; Luo, Ray; Chen, Hai-Feng

2016-04-01

Histone modification plays a key role in gene regulation and gene expression. TRIM24 as a histone reader can recognize histone modification. However the specific recognition mechanism between TRIM24 and histone modification is unsolved. Here, systems biology method of dynamics correlation network based on molecular dynamics simulation was used to answer the question. Our network analysis shows that the dynamics correlation network of H3K23ac is distinctly different from that of wild type and other modifications. A hypothesis of “synergistic modification induced recognition” is then proposed to link histone modification and TRIM24 binding. These observations were further confirmed from community analysis of networks with mutation and network perturbation. Finally, a possible recognition pathway is also identified based on the shortest path search for H3K23ac. Significant difference of recognition pathway was found among different systems due to methylation and acetylation modifications. The analysis presented here and other studies show that the dynamic network-based analysis might be a useful general strategy to study the biology of protein post-translational modification and associated recognition.

Event Horizon Telescope observations as probes for quantum structure of astrophysical black holes

NASA Astrophysics Data System (ADS)

Giddings, Steven B.; Psaltis, Dimitrios

2018-04-01

The need for a consistent quantum evolution for black holes has led to proposals that their semiclassical description is modified not just near the singularity, but at horizon or larger scales. If such modifications extend beyond the horizon, they influence regions accessible to distant observation. Natural candidates for these modifications behave like metric fluctuations, with characteristic length scales and timescales set by the horizon radius. We investigate the possibility of using the Event Horizon Telescope to observe these effects, if they have a strength sufficient to make quantum evolution consistent with unitarity, without introducing new scales. We find that such quantum fluctuations can introduce a strong time dependence for the shape and size of the shadow that a black hole casts on its surrounding emission. For the black hole in the center of the Milky Way, detecting the rapid time variability of its shadow will require nonimaging timing techniques. However, for the much larger black hole in the center of the M87 galaxy, a variable black-hole shadow, if present with these parameters, would be readily observable in the individual snapshots that will be obtained by the Event Horizon Telescope.

N-mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation.

PubMed

Hymbaugh Bergman, Sarah J; Comstock, Lindsay R

2015-08-01

Nucleosomes, the fundamental building blocks of eukaryotic chromatin, undergo post-synthetic modifications and play a major role in the regulation of transcriptional processes. Combinations of these modifications, including methylation, regulate chromatin structure, determining its different functional states and playing a central role in differentiation. The biological significance of cellular methylation, particularly on chromatin, is widely recognized, yet we know little about the mechanisms that link biological methylation events. To characterize and fully understand protein methylation, we describe here novel N-mustard analogs of S-adenosyl-l-methionine (SAM) as biochemical tools to better understand protein arginine methylation events using protein arginine methyltransferase 1 (PRMT1). Specifically, azide- and alkyne-functionalized N-mustard analogs serve as cofactor mimics of SAM and are enzymatically transferred to a model peptide substrate in a PRMT1-dependent fashion. Once incorporated, the resulting alkynes and azides can be modified through chemoselective ligations, including click chemistry and the Staudinger ligation. These results readily demonstrate the feasibility of utilizing N-mustard analogs as biochemical tools to site-specifically label substrates of PRMT1 and serve as an alternative approach to study protein methylation events. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Large-Scale Deployment of Fish Aggregation Devices Alters Environmentally-Based Migratory Behavior of Skipjack Tuna in the Western Pacific Ocean

PubMed Central

Wang, Xuefang; Chen, Yong; Truesdell, Samuel; Xu, Liuxiong; Cao, Jie; Guan, Wenjiang

2014-01-01

Fish aggregation devices (FADs) have been used extensively in the tuna purse seine fishery since the 1980s. This long-term modification of natural habitat has generated discussions as to whether FADs impact movement patterns of tuna species. We examined this question using data collected from the skipjack tuna (Katsuwonus pelamis) fishery. We used the longitudinal gravitational center of catch (G) to examine temporal variability in skipjack movement in the Western and Central Pacific Ocean, and related this to El Niño Southern Oscillation (ENSO) events. We found that in most cases G for free-swimming school sets changed with the onset of ENSO events, while G for floating-object-associated school sets remained relatively constant. This suggests that skipjack exhibit distinguishable behavioral strategies in response to ENSO events: they either react by moving long distances or they associate with floating objects. There has been no previous attempt to evaluate the interaction between FADs and the environmentally-determined movement of skipjack; this study shows evidence of an interaction, which should be considered when managing skipjack populations. PMID:24849561

A modeling tool to evaluate regional coral reef responses to changes in climate and ocean chemistry

USGS Publications Warehouse

Buddemeier, R.W.; Jokiel, P.L.; Zimmerman, K.M.; Lane, D.R.; Carey, J.M.; Bohling, Geoffrey C.; Martinich, J.A.

2008-01-01

We developed a spreadsheet-based model for the use of managers, conservationists, and biologists for projecting the effects of climate change on coral reefs at local-to-regional scales. The COMBO (Coral Mortality and Bleaching Output) model calculates the impacts to coral reefs from changes in average SST and CO2 concentrations, and from high temperature mortality (bleaching) events. The model uses a probabilistic assessment of the frequency of high temperature events under a future climate to address scientific uncertainties about potential adverse effects. COMBO offers data libraries and default factors for three selected regions (Hawai'i, Great Barrier Reef, and Caribbean), but it is structured with user-selectable parameter values and data input options, making possible modifications to reflect local conditions or to incorporate local expertise. Preliminary results from sensitivity analyses and simulation examples for Hawai'i demonstrate the relative importance of high temperature events, increased average temperature, and increased CO2 concentration on the future status of coral reefs; Illustrate significant interactions among variables; and allow comparisons of past environmental history with future predictions. ?? 2008, by the American Society of Limnology and Oceanugraphy, Inc.

Tackling Regional Public Health Issues Using Mobile Health Technology: Event Report of an mHealth Hackathon in Thailand

PubMed Central

Soomlek, Chitsutha; Morley, Katharine; Morley, Michael; Polpinit, Pattarawit; Dagan, Alon; Weis, James W; Celi, Leo Anthony

2017-01-01

Hackathons are intense, short, collaborative events focusing on solving real world problems through interdisciplinary teams. This is a report of the mHealth hackathon hosted by Khon Kaen University in collaboration with MIT Sana and faculty members from Harvard Medical School with the aim to improve health care delivery in the Northeast region of Thailand. Key health challenges, such as improving population health literacy, tracking disease trajectory and outcomes among rural communities, and supporting the workflow of overburdened frontline providers, were addressed using mHealth. Many modifications from the usual format of hackathon were made to tailor the event to the local context and culture, such as the process of recruiting participants and how teams were matched and formed. These modifications serve as good learning points for hosting future hackathons. There are also many lessons learned about how to achieve a fruitful collaboration despite cultural barriers, how to best provide mentorship to the participants, how to instill in the participants a sense of mission, and how to match the participants in a fair and efficient manner. This event showcases how interdisciplinary collaboration can produce results that are unattainable by any discipline alone and demonstrates that innovations are the fruits of collective wisdom of people from different fields of expertise who work together toward the same goals. PMID:29038098

Green Retrofit Technology for Detention Basin Outlet Control Structures

EPA Science Inventory

Urbanization and improperly managed impervious surfaces alters the hydrology of a watershed, leading to increased runoff volumes, higher and/or longer lasting peak flows, and more frequent runoff events. These hydrologic and hydraulic modifications can impact every aspect of stre...

Quantum interference and Monte Carlo simulations of multiparticle production

NASA Astrophysics Data System (ADS)

Bialas, A.; Krzywicki, A.

1995-02-01

We show that the effects of quantum interference can be implemented in Monte Carlo generators by modelling the generalized Wigner functions. A specific prescription for an appropriate modification of the weights of events produced by standard generators is proposed.

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. I. Multimode effect on early membrane events.

PubMed

Rocher, Françoise; Dédaldéchamp, Fabienne; Saeedi, Saed; Fleurat-Lessard, Pierrette; Chollet, Jean-Francois; Roblin, Gabriel

2014-11-01

A study of the structure-activity relationship carried out on several benzoic acid-related phenolics indicates that this type of compounds hinders the osmocontractile reaction of pulvinar cells in the range of 0-100%. Tentatively, we tried to find a way that could explain this differential action. With this aim, the relationship between the inhibitory effect and important molecular physico-chemical parameters (namely lipophilicity and degree of dissociation) was drawn. In addition, the effect of a variety of these compounds was investigated on their capacity to modify the electrical transmembrane potential and induce modifications in proton fluxes. Finally, using plasma membrane vesicles purified from pulvinar tissues, we examined the effects of some selected compounds on the proton pump activity and catalytic activity of the plasma membrane H(+)-ATPase. Taken together, the results indicate that a modification of the molecular structure of phenolics may induce important variation in the activity of the compound on these early membrane events. Among the tested phenolics, salicylic acid (SA) and acetylsalicylic acid (ASA, aspirin) are of particuler note, as they showed atypical effects on the physiological processes studied. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Plasma membrane order and fluidity are diversely triggered by elicitors of plant defence.

PubMed

Sandor, Roman; Der, Christophe; Grosjean, Kevin; Anca, Iulia; Noirot, Elodie; Leborgne-Castel, Nathalie; Lochman, Jan; Simon-Plas, Françoise; Gerbeau-Pissot, Patricia

2016-09-01

Although plants are exposed to a great number of pathogens, they usually defend themselves by triggering mechanisms able to limit disease development. Alongside signalling events common to most such incompatible interactions, modifications of plasma membrane (PM) physical properties could be new players in the cell transduction cascade. Different pairs of elicitors (cryptogein, oligogalacturonides, and flagellin) and plant cells (tobacco and Arabidopsis) were used to address the issue of possible modifications of plant PM biophysical properties induced by elicitors and their links to other events of the defence signalling cascade. We observed an increase of PM order whatever the elicitor/plant cell pair used, provided that a signalling cascade was induced. Such membrane modification is dependent on the NADPH oxidase-mediated reactive oxygen species production. Moreover, cryptogein, which is the sole elicitor able to trap sterols, is also the only one able to trigger an increase in PM fluidity. The use of cryptogein variants with altered sterol-binding properties confirms the strong correlation between sterol removal from the PM and PM fluidity enhancement. These results propose PM dynamics as a player in early signalling processes triggered by elicitors of plant defence. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Measurement of the groomed jet mass in PbPb and pp collisions at $$\\sqrt{s_{_\\mathrm{NN}}} =$$ 5.02 TeV

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

Sirunyan, Albert M; et al.

A measurement of the groomed jet mass in PbPb and pp collisions at a nucleon-nucleon center-of-mass energy of 5.02 TeV with the CMS detector at the LHC is presented. Jet grooming is a recursive procedure which sequentially removes soft constituents of a jet until a pair of hard subjets is found. The resulting groomed jets can be used to study modifications to the parton shower evolution in the presence of the hot and dense medium created in heavy ion collisions. Predictions of groomed jet properties from the PYTHIA and HERWIG++ event generators agree with the measurements in pp collisions. Whenmore » comparing the results from the most central PbPb collisions to pp data, a hint of an increase of jets with large jet mass is observed, which could originate from additional medium-induced radiation at a large angle from the jet axis. However, no modification of the groomed mass of the core of the jet is observed for all PbPb centrality classes. The PbPb results are also compared to predictions from the JEWEL and Q-PYTHIA event generators, which predict a large modification of the groomed mass not observed in the data.« less

Study on Failure of Third-Party Damage for Urban Gas Pipeline Based on Fuzzy Comprehensive Evaluation

PubMed Central

Li, Jun; Zhang, Hong; Han, Yinshan; Wang, Baodong

2016-01-01

Focusing on the diversity, complexity and uncertainty of the third-party damage accident, the failure probability of third-party damage to urban gas pipeline was evaluated on the theory of analytic hierarchy process and fuzzy mathematics. The fault tree of third-party damage containing 56 basic events was built by hazard identification of third-party damage. The fuzzy evaluation of basic event probabilities were conducted by the expert judgment method and using membership function of fuzzy set. The determination of the weight of each expert and the modification of the evaluation opinions were accomplished using the improved analytic hierarchy process, and the failure possibility of the third-party to urban gas pipeline was calculated. Taking gas pipelines of a certain large provincial capital city as an example, the risk assessment structure of the method was proved to conform to the actual situation, which provides the basis for the safety risk prevention. PMID:27875545

Hypoxia-induced oxidative base modifications in the VEGF hypoxia-response element are associated with transcriptionally active nucleosomes.

PubMed

Ruchko, Mykhaylo V; Gorodnya, Olena M; Pastukh, Viktor M; Swiger, Brad M; Middleton, Natavia S; Wilson, Glenn L; Gillespie, Mark N

2009-02-01

Reactive oxygen species (ROS) generated in hypoxic pulmonary artery endothelial cells cause transient oxidative base modifications in the hypoxia-response element (HRE) of the VEGF gene that bear a conspicuous relationship to induction of VEGF mRNA expression (K.A. Ziel et al., FASEB J. 19, 387-394, 2005). If such base modifications are indeed linked to transcriptional regulation, then they should be detected in HRE sequences associated with transcriptionally active nucleosomes. Southern blot analysis of the VEGF HRE associated with nucleosome fractions prepared by micrococcal nuclease digestion indicated that hypoxia redistributed some HRE sequences from multinucleosomes to transcriptionally active mono- and dinucleosome fractions. A simple PCR method revealed that VEGF HRE sequences harboring oxidative base modifications were found exclusively in mononucleosomes. Inhibition of hypoxia-induced ROS generation with myxathiozol prevented formation of oxidative base modifications but not the redistribution of HRE sequences into mono- and dinucleosome fractions. The histone deacetylase inhibitor trichostatin A caused retention of HRE sequences in compacted nucleosome fractions and prevented formation of oxidative base modifications. These findings suggest that the hypoxia-induced oxidant stress directed at the VEGF HRE requires the sequence to be repositioned into mononucleosomes and support the prospect that oxidative modifications in this sequence are an important step in transcriptional activation.

A theoretical model of strong and moderate El Niño regimes

NASA Astrophysics Data System (ADS)

Takahashi, Ken; Karamperidou, Christina; Dewitte, Boris

2018-02-01

The existence of two regimes for El Niño (EN) events, moderate and strong, has been previously shown in the GFDL CM2.1 climate model and also suggested in observations. The two regimes have been proposed to originate from the nonlinearity in the Bjerknes feedback, associated with a threshold in sea surface temperature (T_c ) that needs to be exceeded for deep atmospheric convection to occur in the eastern Pacific. However, although the recent 2015-16 EN event provides a new data point consistent with the sparse strong EN regime, it is not enough to statistically reject the null hypothesis of a unimodal distribution based on observations alone. Nevertheless, we consider the possibility suggestive enough to explore it with a simple theoretical model based on the nonlinear Bjerknes feedback. In this study, we implemented this nonlinear mechanism in the recharge-discharge (RD) ENSO model and show that it is sufficient to produce the two EN regimes, i.e. a bimodal distribution in peak surface temperature (T) during EN events. The only modification introduced to the original RD model is that the net damping is suppressed when T exceeds T_c , resulting in a weak nonlinearity in the system. Due to the damping, the model is globally stable and it requires stochastic forcing to maintain the variability. The sustained low-frequency component of the stochastic forcing plays a key role for the onset of strong EN events (i.e. for T>T_c ), at least as important as the precursor positive heat content anomaly (h). High-frequency forcing helps some EN events to exceed T_c , increasing the number of strong events, but the rectification effect is small and the overall number of EN events is little affected by this forcing. Using the Fokker-Planck equation, we show how the bimodal probability distribution of EN events arises from the nonlinear Bjerknes feedback and also propose that the increase in the net feedback with increasing T is a necessary condition for bimodality in the RD model. We also show that the damping strength determines both the adjustment time-scale and equilibrium value of the ensemble spread associated with the stochastic forcing.

Assessment of the effects of multiple extreme floods on flow and transport processes under competing flood protection and environmental management strategies.

PubMed

Tu, Tongbi; Carr, Kara J; Ercan, Ali; Trinh, Toan; Kavvas, M Levent; Nosacka, John

2017-12-31

Extreme floods are regarded as one of the most catastrophic natural hazards and can result in significant morphological changes induced by pronounced sediment erosion and deposition processes over the landscape. However, the effects of extreme floods of different return intervals on the floodplain and river channel morphological evolution with the associated sediment transport processes are not well explored. Furthermore, different basin management action plans, such as engineering structure modifications, may also greatly affect the flood inundation, sediment transport, solute transport and morphological processes within extreme flood events. In this study, a coupled two-dimensional hydrodynamic, sediment transport and morphological model is applied to evaluate the impact of different river and basin management strategies on the flood inundation, sediment transport dynamics and morphological changes within extreme flood events of different magnitudes. The 10-year, 50-year, 100-year and 200-year floods are evaluated for the Lower Cache Creek system in California under existing condition and a potential future modification scenario. Modeling results showed that select locations of flood inundation within the study area tend to experience larger inundation depth and more sediment is likely to be trapped in the study area under potential modification scenario. The proposed two dimensional flow and sediment transport modeling approach implemented with a variety of inflow conditions can provide guidance to decision-makers when considering implementation of potential modification plans, especially as they relate to competing management strategies of large water bodies, such as the modeling area in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

Redox proteomic evaluation of oxidative modification and recovery in a 3D reconstituted human skin tissue model exposed to UVB.

PubMed

Dyer, J M; Haines, S R; Thomas, A; Wang, W; Walls, R J; Clerens, S; Harland, D P

2017-04-01

Exposure to UV in humans resulting in sunburn triggers a complex series of events that are a mix of immediate and delayed damage mediation and healing. While studies on the effects of UV exposure on DNA damage and repair have been reported, changes in the oxidative modification of skin proteins are poorly understood at the molecular level, despite the important role played by structural proteins in skin tissue, and the effect of the integrity of these proteins on skin appearance and health. Proteomic molecular mapping of oxidation was here applied to try to enhance understanding of skin damage and recovery from oxidative damage and UVB exposure. A redox proteomic-based approach was applied to evaluating skin protein modification when exposed to varying doses of UVB after initial oxidative stress, via tracking changes in protein oxidation during the healing process in vitro using a full-thickness reconstituted human skin tissue model. Bioassays and structural evaluation confirmed that our cultured skin tissues underwent a normal physiological response to UVB exposure. A set of potential skin marker peptides was generated, for use in tracking skin protein oxidative modification. Exposure to UVB after thermal oxidative stress was found to result in higher levels of skin protein oxidation than a non-irradiated control for up to seven days after exposure. Recovery of the skin proteins from oxidative stress, as assessed by the overall protein oxidation levels, was found to be impaired by UVB exposure. Oxidative modification was largely observed in skin structural proteins. Exposure of skin proteins to UVB exacerbates oxidative damage to structural skin proteins, with higher exposure levels leading to increasingly impaired recovery from this damage. This has potential implications for the functional performance of the proteins and inter-related skin health and cosmetic appearance. © 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

DOE PAGES

Schumann, Kathrin; Lin, Steven; Boyer, Eric; ...

2015-07-27

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4 + T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs).more » Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 ( PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

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

Schumann, Kathrin; Lin, Steven; Boyer, Eric

T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4 + T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs).more » Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 ( PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

Patrick Air Force Base Storm Water Pollution Prevention Plan.

DTIC Science & Technology

1994-09-01

CE 00 0O L 2- E0 .0 cl ci = 0 L) cz C C 00 H cz - ~.CIn U -. 0 0 - - E o nC .C) 0 2;l C)i En C) u C CIO cz _ C>) C) 0 u E-) a) Z L) 0o~bo coo 0 - . cn...as soon as practi-distated and lo dal c rq ir nts anderas, cable after significant modification areS tate, an d local req u irem en ts an d asm a e t...the duration between the storm event and fecal coliform (counts per 100 mL). sampled and the end of the previous measur- able (greater than 0.1 inch

An Overview of the Chemistry and Biology of Reactive Aldehydes

PubMed Central

Fritz, Kristofer S.; Petersen, Dennis R.

2012-01-01

The non-enzymatic free radical generation of reactive aldehydes is known to contribute to diseases of sustained oxidative stress including rheumatoid arthritis, atherosclerosis, neurodegenerative and a number of liver diseases. At the same time, the accumulation of lipid electrophiles has been demonstrated to play a role in cell signaling events through modification of proteins critical for cellular homeostasis. Given the broad scope of reactivity profiles and the ability to modify numerous proteomic and genomic processes, new emphasis is being placed on a systems-based analysis of the consequences of electrophilic adduction. This review focuses on the generation and chemical reactivity of lipid-derived aldehydes with a special focus on the homeostatic responses to electrophilic stress. PMID:22750507

Directional Antineutrino Detection

NASA Astrophysics Data System (ADS)

Safdi, Benjamin R.; Suerfu, Burkhant

2015-02-01

We propose the first event-by-event directional antineutrino detector using inverse beta decay (IBD) interactions on hydrogen, with potential applications including monitoring for nuclear nonproliferation, spatially mapping geoneutrinos, characterizing the diffuse supernova neutrino background and searching for new physics in the neutrino sector. The detector consists of adjacent and separated target and capture scintillator planes. IBD events take place in the target layers, which are thin enough to allow the neutrons to escape without scattering elastically. The neutrons are detected in the thicker boron-loaded capture layers. The location of the IBD event and the momentum of the positron are determined by tracking the positron's trajectory through the detector. Our design is a straightforward modification of existing antineutrino detectors; a prototype could be built with existing technology.

77 FR 61539 - Airworthiness Directives; DASSAULT AVIATION Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-10

... the area of the wheel well. We are proposing this AD to prevent fuel spillage in the event of a MLG... modification of the wing fuel tanks in the area of the wheel well which introduces a dry bay by adding a sealed...

La Niña diversity and Northwest Indian Ocean Rim teleconnections

USGS Publications Warehouse

Hoell, Andrew; Funk, Christopher C.; Barlow, Mathew

2014-01-01

The differences in tropical Pacific sea surface temperature (SST) expressions of El Niño-Southern Oscillation (ENSO) events of the same phase have been linked with different global atmospheric circulation patterns. This study examines the dynamical forcing of precipitation during October–December (OND) and March–May (MAM) over East Africa and during December–March (DJFM) over Central-Southwest Asia for 1950–2010 associated with four tropical Pacific SST patterns characteristic of La Niña events, the cold phase of ENSO. The self-organizing map method along with a statistical distinguishability test was used to isolate La Niña events, and seasonal precipitation forcing was investigated in terms of the tropical overturning circulation and thermodynamic and moisture budgets. Recent La Niña events with strong opposing SST anomalies between the central and western Pacific Ocean (phases 3 and 4), force the strongest global circulation modifications and drought over the Northwest Indian Ocean Rim. Over East Africa during MAM and OND, subsidence is forced by an enhanced tropical overturning circulation and precipitation reductions are exacerbated by increases in moisture flux divergence. Over Central-Southwest Asia during DJFM, the thermodynamic forcing of subsidence is primarily responsible for precipitation reductions, with moisture flux divergence acting as a secondary mechanism to reduce precipitation. Eastern Pacific La Niña events in the absence of west Pacific SST anomalies (phases 1 and 2), are associated with weaker global teleconnections, particularly over the Indian Ocean Rim. The weak regional teleconnections result in statistically insignificant precipitation modifications over East Africa and Central-Southwest Asia.

Walking and talking the tree of life: Why and how to teach about biodiversity.

PubMed

Ballen, Cissy J; Greene, Harry W

2017-03-01

Taxonomic details of diversity are an essential scaffolding for biology education, yet outdated methods for teaching the tree of life (TOL), as implied by textbook content and usage, are still commonly employed. Here, we show that the traditional approach only vaguely represents evolutionary relationships, fails to denote major events in the history of life, and relies heavily on memorizing near-meaningless taxonomic ranks. Conversely, a clade-based strategy-focused on common ancestry, monophyletic groups, and derived functional traits-is explicitly based on Darwin's "descent with modification," provides students with a rational system for organizing the details of biodiversity, and readily lends itself to active learning techniques. We advocate for a phylogenetic classification that mirrors the TOL, a pedagogical format of increasingly complex but always hierarchical presentations, and the adoption of active learning technologies and tactics.

Mitogen- and Stress-Activated Kinase 1 (MSK1) Regulates Cigarette Smoke-Induced Histone Modifications on NF-κB-dependent Genes

PubMed Central

Sundar, Isaac K.; Chung, Sangwoon; Hwang, Jae-woong; Lapek, John D.; Bulger, Michael; Friedman, Alan E.; Yao, Hongwei; Davie, James R.; Rahman, Irfan

2012-01-01

Cigarette smoke (CS) causes sustained lung inflammation, which is an important event in the pathogenesis of chronic obstructive pulmonary disease (COPD). We have previously reported that IKKα (I kappaB kinase alpha) plays a key role in CS-induced pro-inflammatory gene transcription by chromatin modifications; however, the underlying role of downstream signaling kinase is not known. Mitogen- and stress-activated kinase 1 (MSK1) serves as a specific downstream NF-κB RelA/p65 kinase, mediating transcriptional activation of NF-κB-dependent pro-inflammatory genes. The role of MSK1 in nuclear signaling and chromatin modifications is not known, particularly in response to environmental stimuli. We hypothesized that MSK1 regulates chromatin modifications of pro-inflammatory gene promoters in response to CS. Here, we report that CS extract activates MSK1 in human lung epithelial (H292 and BEAS-2B) cell lines, human primary small airway epithelial cells (SAEC), and in mouse lung, resulting in phosphorylation of nuclear MSK1 (Thr581), phospho-acetylation of RelA/p65 at Ser276 and Lys310 respectively. This event was associated with phospho-acetylation of histone H3 (Ser10/Lys9) and acetylation of histone H4 (Lys12). MSK1 N- and C-terminal kinase-dead mutants, MSK1 siRNA-mediated knock-down in transiently transfected H292 cells, and MSK1 stable knock-down mouse embryonic fibroblasts significantly reduced CS extract-induced MSK1, NF-κB RelA/p65 activation, and posttranslational modifications of histones. CS extract/CS promotes the direct interaction of MSK1 with RelA/p65 and p300 in epithelial cells and in mouse lung. Furthermore, CS-mediated recruitment of MSK1 and its substrates to the promoters of NF-κB-dependent pro-inflammatory genes leads to transcriptional activation, as determined by chromatin immunoprecipitation. Thus, MSK1 is an important downstream kinase involved in CS-induced NF-κB activation and chromatin modifications, which have implications in pathogenesis of COPD. PMID:22312446

Big Events in Greece and HIV Infection Among People Who Inject Drugs

PubMed Central

Nikolopoulos, Georgios K.; Sypsa, Vana; Bonovas, Stefanos; Paraskevis, Dimitrios; Malliori-Minerva, Melpomeni; Hatzakis, Angelos; Friedman, Samuel R.

2015-01-01

Big Events are processes like macroeconomic transitions that have lowered social well-being in various settings in the past. Greece has been hit by the global crisis and experienced an HIV outbreak among people who inject drugs. Since the crisis began (2008), Greece has seen population displacement, inter-communal violence, cuts in governmental expenditures, and social movements. These may have affected normative regulation, networks, and behaviors. However, most pathways to risk remain unknown or unmeasured. We use what is known and unknown about the Greek HIV outbreak to suggest modifications in Big Events models and the need for additional research. PMID:25723309

Sedimentary Characteristics Relating To Artificially Intensified Flow Patterns At Dona And Roberts Bay, West-central Florida

NASA Astrophysics Data System (ADS)

Kelso, K. W.; Wang, P.

2006-12-01

The Dona and Roberts Bay connects one of the five major watersheds in Sarasota County Florida to the Gulf of Mexico via the Venice Inlet. Like many watersheds in the area, significant modifications have been made to the drainage basins, principally to the main tributaries. Many of the creeks that comprise the watershed have been dammed in order to inhibit the upstream flow of salt water. They are also deepened or lengthened to allow better drainage. In addition, there are numerous oyster bars, as well as artificial structures that impose obstruction to the tidal and river flows. These have resulted in a complex sedimentation and erosion pattern with substantial anthropogenic influences. The objectives of this study are to quantify the sediment characteristics and deposition-erosion trends and their relationship to the flow patterns. A detailed sedimentary analysis was conducted based on 149 surface sediment samples and 29 drill cores. Spatial distribution of the sediment properties is quite complex, controlled by several interactive factors including local sediment supply, intensity of the hydrodynamic processes, distribution of oyster bars and mangrove islands, and artificial structures. Sedimentation and erosion is significantly influenced by flood events. The core data suggest that rapid sedimentation driven by flood events is responsible for the development of some of the large shoals. A 2- D depth-averaged circulation model was established for the study area on a bathymetry that was surveyed by this study. Many of the artificial modifications to the watershed system are incorporated. A close relationship between the flow intensity and sediment characteristics and sedimentation-erosion tendency is identified.

A mobile phone-based care model for outpatient cardiac rehabilitation: the care assessment platform (CAP).

PubMed

Walters, Darren L; Sarela, Antti; Fairfull, Anita; Neighbour, Kylie; Cowen, Cherie; Stephens, Belinda; Sellwood, Tom; Sellwood, Bernadette; Steer, Marie; Aust, Michelle; Francis, Rebecca; Lee, Chi-Keung; Hoffman, Sheridan; Brealey, Gavin; Karunanithi, Mohan

2010-01-28

Cardiac rehabilitation programs offer effective means to prevent recurrence of a cardiac event, but poor uptake of current programs have been reported globally. Home based models are considered as a feasible alternative to avoid various barriers related to care centre based programs. This paper sets out the study design for a clinical trial seeking to test the hypothesis that these programs can be better and more efficiently supported with novel Information and Communication Technologies (ICT). We have integrated mobile phones and web services into a comprehensive home- based care model for outpatient cardiac rehabilitation. Mobile phones with a built-in accelerometer sensor are used to measure physical exercise and WellnessDiary software is used to collect information on patients' physiological risk factors and other health information. Video and teleconferencing are used for mentoring sessions aiming at behavioural modifications through goal setting. The mentors use web-portal to facilitate personal goal setting and to assess the progress of each patient in the program. Educational multimedia content are stored or transferred via messaging systems to the patients phone to be viewed on demand. We have designed a randomised controlled trial to compare the health outcomes and cost efficiency of the proposed model with a traditional community based rehabilitation program. The main outcome measure is adherence to physical exercise guidelines. The study will provide evidence on using mobile phones and web services for mentoring and self management in a home-based care model targeting sustainable behavioural modifications in cardiac rehabilitation patients. The trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with number ACTRN12609000251224.

A mobile phone-based care model for outpatient cardiac rehabilitation: the care assessment platform (CAP)

PubMed Central

2010-01-01

Background Cardiac rehabilitation programs offer effective means to prevent recurrence of a cardiac event, but poor uptake of current programs have been reported globally. Home based models are considered as a feasible alternative to avoid various barriers related to care centre based programs. This paper sets out the study design for a clinical trial seeking to test the hypothesis that these programs can be better and more efficiently supported with novel Information and Communication Technologies (ICT). Methods/Design We have integrated mobile phones and web services into a comprehensive home- based care model for outpatient cardiac rehabilitation. Mobile phones with a built-in accelerometer sensor are used to measure physical exercise and WellnessDiary software is used to collect information on patients' physiological risk factors and other health information. Video and teleconferencing are used for mentoring sessions aiming at behavioural modifications through goal setting. The mentors use web-portal to facilitate personal goal setting and to assess the progress of each patient in the program. Educational multimedia content are stored or transferred via messaging systems to the patients phone to be viewed on demand. We have designed a randomised controlled trial to compare the health outcomes and cost efficiency of the proposed model with a traditional community based rehabilitation program. The main outcome measure is adherence to physical exercise guidelines. Discussion The study will provide evidence on using mobile phones and web services for mentoring and self management in a home-based care model targeting sustainable behavioural modifications in cardiac rehabilitation patients. Trial registration The trial has been registered in the Australian New Zealand Clinical Trials Registry (ANZCTR) with number ACTRN12609000251224. PMID:20109196

The Search for Muon Neutrinos from Northern Hemisphere Gamma-Ray Bursts with AMANDA

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

Achterberg, A.; Ackermann, M.; Bernardini, E.

2008-02-10

We present the results of the analysis of neutrino observations by the Antarctic Muon and Neutrino Detector Array (AMANDA) correlated with photon observations of more than 400 gamma-ray bursts (GRBs) in the northern hemisphere from 1997 to 2003. During this time period, AMANDA's effective collection area for muon neutrinos was larger than that of any other existing detector. After the application of various selection criteria to our data, we expect {approx}1 neutrino event and <2 background events. Based on our observations of zero events during and immediately prior to the GRBs in the data set, we set the most stringentmore » upper limit on muon neutrino emission correlated with GRBs. Assuming a Waxman-Bahcall spectrum and incorporating all systematic uncertainties, our flux upper limit has a normalization at 1 PeV of E{sup 2}{phi}{sub {nu}} {<=} 6.3 x 10{sup -9} GeV cm{sup -2} s{sup -1} sr{sup -1}, with 90% of the events expected within the energy range of {approx}10 TeV to {approx}3 PeV. The impact of this limit on several theoretical models of GRBs is discussed, as well as the future potential for detection of GRBs by next-generation neutrino telescopes. Finally, we briefly describe several modifications to this analysis in order to apply it to other types of transient point sources.« less

Commerical Crew Astronauts Visit Launch Complex 39A

NASA Image and Video Library

2018-03-27

Commercial Crew Program astronauts, from the left, Suni Williams, Eric Boe, Bob Behnken and Doug Hurley take in the view from the top of Launch Complex 39A at Kennedy Space Center. The astronauts toured the pad for an up-close look at modifications that are in work for the SpaceX Crew Dragon flight tests. Tower modifications included l removal of the space shuttle era rotating service structure. Future integration of the crew access arm will allow for safe crew entry for launch and exit from the spacecraft in the unlikely event a pad abort is required.

Commerical Crew Astronauts Visit Launch Complex 39A

NASA Image and Video Library

2018-03-27

Commercial Crew Program astronauts, from the left Doug Hurley, Eric Boe, Bob Behnken and Suni Williams, pose just outside Launch Complex 39A at NASA's Kennedy Space Center in Florida. The astronauts toured the pad for an up-close look at modifications that are in work for the SpaceX Crew Dragon flight tests. The tower modifications included removal of the space shuttle era rotating service structure. Future integration of the crew access arm will allow for safe crew entry for launch and exit from the spacecraft in the unlikely event a pad abort is required.

Connexins: Synthesis, Post-Translational Modifications, and Trafficking in Health and Disease

PubMed Central

Vidal-Brime, Laia; Lynn, K. Sabrina

2018-01-01

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function, and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability, and function. Here, we summarize these key regulatory events, with emphasis on how these affect connexin multifunctionality in health and disease. PMID:29701678

Enhanced object-based tracking algorithm for convective rain storms and cells

NASA Astrophysics Data System (ADS)

Muñoz, Carlos; Wang, Li-Pen; Willems, Patrick

2018-03-01

This paper proposes a new object-based storm tracking algorithm, based upon TITAN (Thunderstorm Identification, Tracking, Analysis and Nowcasting). TITAN is a widely-used convective storm tracking algorithm but has limitations in handling small-scale yet high-intensity storm entities due to its single-threshold identification approach. It also has difficulties to effectively track fast-moving storms because of the employed matching approach that largely relies on the overlapping areas between successive storm entities. To address these deficiencies, a number of modifications are proposed and tested in this paper. These include a two-stage multi-threshold storm identification, a new formulation for characterizing storm's physical features, and an enhanced matching technique in synergy with an optical-flow storm field tracker, as well as, according to these modifications, a more complex merging and splitting scheme. High-resolution (5-min and 529-m) radar reflectivity data for 18 storm events over Belgium are used to calibrate and evaluate the algorithm. The performance of the proposed algorithm is compared with that of the original TITAN. The results suggest that the proposed algorithm can better isolate and match convective rainfall entities, as well as to provide more reliable and detailed motion estimates. Furthermore, the improvement is found to be more significant for higher rainfall intensities. The new algorithm has the potential to serve as a basis for further applications, such as storm nowcasting and long-term stochastic spatial and temporal rainfall generation.

Diverse and divergent protein post-translational modifications in two growth stages of a natural microbial community

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

Li, Zhou; Wang, Yingfeng; Yao, Qiuming

2014-01-01

Detailed characterization of posttranslational modifications (PTMs) of proteins in microbial communities remains a significant challenge. Here we directly identify and quantify a broad range of PTMs (hydroxylation, methylation, citrullination, acetylation, phosphorylation, methylthiolation, S-nitrosylation and nitration) in a natural microbial community from an acid mine drainage site. Approximately 29% of the identified proteins of the dominant Leptospirillum group II bacteria are modified, and 43% of modified proteins carry multiple PTM types. Most PTM events, except S-nitrosylations, have low fractional occupancy. Notably, PTM events are detected on Cas proteins involved in antiviral defense, an aspect of Cas biochemistry not considered previously. Further,more » Cas PTM profiles from Leptospirillum group II differ in early versus mature biofilms. PTM patterns are divergent on orthologues of two closely related, but ecologically differentiated, Leptospirillum group II bacteria. Our results highlight the prevalence and dynamics of PTMs of proteins, with potential significance for ecological adaptation and microbial evolution.« less

Epigenetic modifications in prostate cancer.

PubMed

Ngollo, Marjolaine; Dagdemir, Aslihan; Karsli-Ceppioglu, Seher; Judes, Gaelle; Pajon, Amaury; Penault-Llorca, Frederique; Boiteux, Jean-Paul; Bignon, Yves-Jean; Guy, Laurent; Bernard-Gallon, Dominique J

2014-01-01

Prostate cancer is the most common cancer in men and the second leading cause of cancer deaths in men in France. Apart from the genetic alterations in prostate cancer, epigenetics modifications are involved in the development and progression of this disease. Epigenetic events are the main cause in gene regulation and the three most epigenetic mechanisms studied include DNA methylation, histone modifications and microRNA expression. In this review, we summarized epigenetic mechanisms in prostate cancer. Epigenetic drugs that inhibit DNA methylation, histone methylation and histone acetylation might be able to reactivate silenced gene expression in prostate cancer. However, further understanding of interactions of these enzymes and their effects on transcription regulation in prostate cancer is needed and has become a priority in biomedical research. In this study, we summed up epigenetic changes with emphasis on pharmacologic epigenetic target agents.

Vaccinations and multiple sclerosis.

PubMed

Gout, O

2001-04-01

Two problems must be considered in regard to the relationship between vaccinations and MS: Do vaccinations favour the first attack of MS? Do they increase the short- or long-term risk in patients with known disease? Answers to these questions are difficult due to the paucity of reported cases, our ignorance of the precise frequency of neurological adverse events in vaccines based on prospective studies, and finally by the lack of a well established pathophysiology. In most instances, the role of the vaccine is based on a temporal link between the injection and the onset of neurological disease, and more rarely to a positive reintroduction. Acute disseminated encephalomyelitis (ADEM), a monophasic and multifocal illness of the white and grey matter, has been observed following various viral or bacterial infections as well as vaccine injections for diseases such as pertussis, tetanus and yellow fever. The similarities between ADEM and experimental allergic encephalitis (EAE) are suggestive of an immunological process. In addition to the dramatic presentation of ADEM, more limited white matter involvement, such as optic neuritis or myelitis, has been reported following vaccine injections, and has occasionally been counted as the first attack of MS. In France, 25 million inhabitants, almost half of the population, were vaccinated against hepatitis B (HB) between 1991 and 1999. Several hundred cases of an acute central demyelinating event following HB vaccination were reported to the pharmacovigilance unit, leading to a modification of vaccination policy in the schools and the initiation of several studies designed to examine the possible relationship between the vaccine and the central demyelinating events. The results of these studies failed to establish the causality of the HB vaccine. Nevertheless, molecular mimicry between HB antigen(s) and one or more myelin proteins, or a non-specific activation of autoreactive lymphocytes, could constitute possible pathogenetic mechanisms for these adverse neurological events.

Polysomnographic findings in a cohort of chronic insomnia patients with benzodiazepine abuse.

PubMed

Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Marano, Giuseppe; Di Nicola, Marco; Dittoni, Serena; Gnoni, Valentina; Di Blasi, Chiara; Giannantoni, Nadia Mariagrazia; Lapenta, Leonardo; Brunetti, Valerio; Bria, Pietro; Janiri, Luigi; Mazza, Salvatore; Della Marca, Giacomo

2014-01-15

To evaluate sleep modifications induced by chronic benzodiazepine (BDZ) abuse. Cohort study, comparison of sleep measures between BDZs abusers and controls. Drug Addiction Unit (Institute of Psychiatry) and Unit of Sleep Disorders (Institute of Neurology) of the Catholic University in Rome. Six outpatients affected by chronic BDZ abuse were enrolled, (4 men, 2 women, mean age 53.3 ± 14.8, range: 34-70 years); 55 healthy controls were also enrolled (23 men, 32 women, mean age 54.2 ± 13.0, range: 27-76 years). All patients underwent clinical evaluation, psychometric measures, ambulatory polysomnography, scoring of sleep macrostructure and microstructure (power spectral fast-frequency EEG arousal, cyclic alternating pattern [CAP]), and heart rate variability. BDZ abusers had relevant modification of sleep macrostructure and a marked reduction of fast-frequency EEG arousal in NREM (patients: 6.6 ± 3.7 events/h, controls 13.7 ± 4.9 events/h, U-test: 294, p = 0.002) and REM (patients: 8.4 ± 2.4 events/h, controls 13.3 ± 5.1 events/h, U-test: 264, p = 0.016), and of CAP rate (patients: 15.0 ± 8.6%, controls: 51.2% ± 12.1%, U-test: 325, p < 0.001). BDZ abusers have reduction of arousals associated with increased number of nocturnal awakenings and severe impairment of sleep architecture. The effect of chronic BDZ abuse on sleep may be described as a severe impairment of arousal dynamics; the result is the inability to modulate levels of vigilance.

Epigenetics and depression: return of the repressed.

PubMed

Dalton, Victoria S; Kolshus, Erik; McLoughlin, Declan M

2014-02-01

Epigenetics has recently emerged as a potential mechanism by which adverse environmental stimuli can result in persistent changes in gene expression. Epigenetic mechanisms function alongside the DNA sequence to modulate gene expression and ultimately influence protein production. The current review provides an introduction and overview of epigenetics with a particular focus on preclinical and clinical studies relevant to major depressive disorder (MDD). PubMed and Web of Science databases were interrogated from January 1995 up to December 2012 using combinations of search terms, including "epigenetic", "microRNA" and "DNA methylation" cross referenced with "depression", "early life stress" and "antidepressant". There is an association between adverse environmental stimuli, such as early life stress, and epigenetic modification of gene expression. Epigenetic changes have been reported in humans with MDD and may serve as biomarkers to improve diagnosis. Antidepressant treatments appear to reverse or initiate compensatory epigenetic alterations that may be relevant to their mechanism of action. As a narrative review, the current report was interpretive and qualitative in nature. Epigenetic modification of gene expression provides a mechanism for understanding the link between long-term effects of adverse life events and the changes in gene expression that are associated with depression. Although still a developing field, in the future, epigenetic modifications of gene expression may provide novel biomarkers to predict future susceptibility and/or onset of MDD, improve diagnosis, and aid in the development of epigenetics-based therapies for depression. © 2013 Published by Elsevier B.V.

Does behaviour modification affect post-stroke risk factor control? Three-year follow-up of a randomized controlled trial.

PubMed

McManus, Julie Ann; Craig, Alison; McAlpine, Christine; Langhorne, Peter; Ellis, Graham

2009-02-01

Little is known about the long-term effectiveness after stroke of interventions for behaviour modification and ensuring concordance with therapies. We describe a follow-up study of a previous randomized controlled trial of a brief period of behaviour modification. The aim of this study was to determine outcomes three years after the initial intervention. Survivors of the original cohort were contacted and asked to attend for follow-up interview, within a geriatric day hospital. This study was carried out in the Geriatric Day Hospital at Stobhill Hospital, Balornock Road, Glasgow. Details of risk factor control, including blood pressure, cholesterol levels and diabetic control, were assessed. Questionnaires used in the initial study were repeated including the Geriatric Depression Scale score, Euroqol Perceived Health Status and Stroke Services Satisfaction Questionnaire. Primary outcome was collective risk factor control. Clinical outcomes including recurrent cerebrovascular events, medication persistence and perceived health status were also recorded. Mean length of follow-up was 3.6 years (SD 0.43). Of the 205 patients enrolled in the initial study, 102 patients attended for repeat interview(49 intervention/53 control). There were no significant differences in the percentage of controlled risk factors between groups (intervention 51.7% versus control 55.9%, P = 0.53). Similarities were observed in the number of recurrent clinical events and medication persistence between groups. No overall difference was observed in perceived health status, satisfaction with care or depression scores. Brief intervention with respect to behaviour modification and risk factor control does not appear to have any long-term benefit. These results must be cautiously interpreted in light of the small study number and further research is required.

Horizontal and vertical structure of reactive bromine events probed by bromine monoxide MAX-DOAS

NASA Astrophysics Data System (ADS)

Simpson, William R.; Peterson, Peter K.; Frieß, Udo; Sihler, Holger; Lampel, Johannes; Platt, Ulrich; Moore, Chris; Pratt, Kerri; Shepson, Paul; Halfacre, John; Nghiem, Son V.

2017-08-01

Heterogeneous photochemistry converts bromide (Br-) to reactive bromine species (Br atoms and bromine monoxide, BrO) that dominate Arctic springtime chemistry. This phenomenon has many impacts such as boundary-layer ozone depletion, mercury oxidation and deposition, and modification of the fate of hydrocarbon species. To study environmental controls on reactive bromine events, the BRomine, Ozone, and Mercury EXperiment (BROMEX) was carried out from early March to mid-April 2012 near Barrow (Utqiaġvik), Alaska. We measured horizontal and vertical gradients in BrO with multiple-axis differential optical absorption spectroscopy (MAX-DOAS) instrumentation at three sites, two mobile and one fixed. During the campaign, a large crack in the sea ice (an open lead) formed pushing one instrument package ˜ 250 km downwind from Barrow (Utqiaġvik). Convection associated with the open lead converted the BrO vertical structure from a surface-based event to a lofted event downwind of the lead influence. The column abundance of BrO downwind of the re-freezing lead was comparable to upwind amounts, indicating direct reactions on frost flowers or open seawater was not a major reactive bromine source. When these three sites were separated by ˜ 30 km length scales of unbroken sea ice, the BrO amount and vertical distributions were highly correlated for most of the time, indicating the horizontal length scales of BrO events were typically larger than ˜ 30 km in the absence of sea ice features. Although BrO amount and vertical distribution were similar between sites most of the time, rapid changes in BrO with edges significantly smaller than this ˜ 30 km length scale episodically transported between the sites, indicating BrO events were large but with sharp edge contrasts. BrO was often found in shallow layers that recycled reactive bromine via heterogeneous reactions on snowpack. Episodically, these surface-based events propagated aloft when aerosol extinction was higher (> 0.1 km-1); however, the presence of aerosol particles aloft was not sufficient to produce BrO aloft. Highly depleted ozone (< 1 nmol mol-1) repartitioned reactive bromine away from BrO and drove BrO events aloft in cases. This work demonstrates the interplay between atmospheric mixing and heterogeneous chemistry that affects the vertical structure and horizontal extent of reactive bromine events.

Heterochrony, cannibalism, and the evolution of viviparity in Salamandra salamandra.

PubMed

Buckley, David; Alcobendas, Marina; García-París, Mario; Wake, Marvalee H

2007-01-01

The way in which novelties that lead to macroevolutionary events originate is a major question in evolutionary biology, and one that can be addressed using the fire salamander (Salamandra salamandra) as a model system. It is exceptional among amphibians in displaying intraspecific diversity of reproductive strategies. In S. salamandra, two distinct modes of reproduction co-occur: the common mode, ovoviviparity (females giving birth to many small larvae), and a phylogenetically derived reproductive strategy, viviparity (females producing only a few large, fully metamorphosed juveniles, which are nourished maternally). We examine the relationship between heterochronic modifications of the ontogeny and the evolution of the new reproductive mode in the fire salamander. The in vitro development of embryos of ovoviviparous and viviparous salamanders from fertilization to metamorphosis is compared, highlighting the key events that distinguish the two modes of reproduction. We identify the heterochronic events that, together with the intrauterine cannibalistic behavior, characterize the derived viviparous reproductive strategy. The ways in which evolutionary novelties can arise by modification of developmental programs can be studied in S. salamandra. Moreover, the variation in reproductive modes and the associated variation of sequences of development occur in neighboring, conspecific populations. Thus, S. salamandra is a unique biological system in which evolutionary developmental research questions can be addressed at the level of populations.

Reducing depressive intrusions via a computerized cognitive bias modification of appraisals task: developing a cognitive vaccine.

PubMed

Lang, Tamara J; Moulds, Michelle L; Holmes, Emily A

2009-02-01

A feature of depression is the distressing experience of intrusive, negative memories. The maladaptive appraisals of such intrusions have been associated with symptom persistence. This study aimed to experimentally manipulate appraisals about depressive intrusions via a novel computerized cognitive bias modification (CBM) of appraisals paradigm, and to test the impact on depressive intrusion frequency for a standardized event (a depressive film). Forty-eight participants were randomly assigned to either a session of positive or negative CBM. Participants then watched a depressing film (including scenes of bereavement and bullying) and subsequently monitored the occurrence of depressive intrusions related to the film in a diary for one week. At one-week follow-up, participants completed additional measures of intrusions--the Impact of Event Scale (IES) and an intrusion provocation task. As predicted, compared to the negative condition, participants who underwent positive CBM showed a more positive appraisal bias. Further, one week later, positive CBM participants reported fewer intrusions of the film and had lower IES scores. Our findings demonstrate that it is possible to manipulate maladaptive appraisals about depressive intrusions via a computerized CBM task. Further, this effect transfers to reducing intrusive symptomatology related to a standardized event (a depressive film) over one week, suggesting novel clinical implications.

Combining joint models for biomedical event extraction

PubMed Central

2012-01-01

Background We explore techniques for performing model combination between the UMass and Stanford biomedical event extraction systems. Both sub-components address event extraction as a structured prediction problem, and use dual decomposition (UMass) and parsing algorithms (Stanford) to find the best scoring event structure. Our primary focus is on stacking where the predictions from the Stanford system are used as features in the UMass system. For comparison, we look at simpler model combination techniques such as intersection and union which require only the outputs from each system and combine them directly. Results First, we find that stacking substantially improves performance while intersection and union provide no significant benefits. Second, we investigate the graph properties of event structures and their impact on the combination of our systems. Finally, we trace the origins of events proposed by the stacked model to determine the role each system plays in different components of the output. We learn that, while stacking can propose novel event structures not seen in either base model, these events have extremely low precision. Removing these novel events improves our already state-of-the-art F1 to 56.6% on the test set of Genia (Task 1). Overall, the combined system formed via stacking ("FAUST") performed well in the BioNLP 2011 shared task. The FAUST system obtained 1st place in three out of four tasks: 1st place in Genia Task 1 (56.0% F1) and Task 2 (53.9%), 2nd place in the Epigenetics and Post-translational Modifications track (35.0%), and 1st place in the Infectious Diseases track (55.6%). Conclusion We present a state-of-the-art event extraction system that relies on the strengths of structured prediction and model combination through stacking. Akin to results on other tasks, stacking outperforms intersection and union and leads to very strong results. The utility of model combination hinges on complementary views of the data, and we show that our sub-systems capture different graph properties of event structures. Finally, by removing low precision novel events, we show that performance from stacking can be further improved. PMID:22759463

Modern and prospective technologies for weather modification activities: A look at integrating unmanned aircraft systems

NASA Astrophysics Data System (ADS)

Axisa, Duncan; DeFelice, Tom P.

2016-09-01

Present-day weather modification technologies are scientifically based and have made controlled technological advances since the late 1990s, early 2000s. The technological advances directly related to weather modification have primarily been in the decision support and evaluation based software and modeling areas. However, there have been some technological advances in other fields that might now be advanced enough to start considering their usefulness for improving weather modification operational efficiency and evaluation accuracy. We consider the programmatic aspects underlying the development of new technologies for use in weather modification activities, identifying their potential benefits and limitations. We provide context and initial guidance for operators that might integrate unmanned aircraft systems technology in future weather modification operations.

[Epigenetic alterations in acute lymphoblastic leukemia].

PubMed

Navarrete-Meneses, María Del Pilar; Pérez-Vera, Patricia

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. It is well-known that genetic alterations constitute the basis for the etiology of ALL. However, genetic abnormalities are not enough for the complete development of the disease, and additional alterations such as epigenetic modifications are required. Such alterations, like DNA methylation, histone modifications, and noncoding RNA regulation have been identified in ALL. DNA hypermethylation in promoter regions is one of the most frequent epigenetic modifications observed in ALL. This modification frequently leads to gene silencing in tumor suppressor genes, and in consequence, contributes to leukemogenesis. Alterations in histone remodeling proteins have also been detected in ALL, such as the overexpression of histone deacetylases enzymes, and alteration of acetyltransferases and methyltransferases. ALL also shows alteration in the expression of miRNAs, and in consequence, the modification in the expression of their target genes. All of these epigenetic modifications are key events in the malignant transformation since they lead to the deregulation of oncogenes as BLK, WNT5B and WISP1, and tumor suppressors such as FHIT, CDKN2A, CDKN2B, and TP53, which alter fundamental cellular processes and potentially lead to the development of ALL. Both genetic and epigenetic alterations contribute to the development and evolution of ALL. Copyright © 2017 Hospital Infantil de México Federico Gómez. Publicado por Masson Doyma México S.A. All rights reserved.

[Genotoxic modification of nucleic acid bases and biological consequences of it. Review and prospects of experimental and computational investigations

NASA Technical Reports Server (NTRS)

Poltev, V. I.; Bruskov, V. I.; Shuliupina, N. V.; Rein, R.; Shibata, M.; Ornstein, R.; Miller, J.

1993-01-01

The review is presented of experimental and computational data on the influence of genotoxic modification of bases (deamination, alkylation, oxidation) on the structure and biological functioning of nucleic acids. Pathways are discussed for the influence of modification on coding properties of bases, on possible errors of nucleic acid biosynthesis, and on configurations of nucleotide mispairs. The atomic structure of nucleic acid fragments with modified bases and the role of base damages in mutagenesis and carcinogenesis are considered.

Preoperative hydronephrosis is associated with less decline in renal function after radical nephroureterectomy for upper tract urothelial carcinoma.

PubMed

Singla, Nirmish; Hutchinson, Ryan; Haddad, Ahmed; Sagalowsky, Arthur; Lotan, Yair; Margulis, Vitaly

2016-08-01

To compare renal function changes after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC) based on the presence of preoperative hydronephrosis. Clinicopathologic data of 208 patients with UTUC treated surgically from 1998 to 2013 were compiled. Patients with bilateral disease, less than 1 month follow up, missing hydronephrosis data, or who underwent nephron-sparing approaches were excluded. Estimated glomerular filtration rate (eGFR) was calculated preoperatively, at first follow up (within 3 months) and at last follow up using the Modification of Diet in Renal Disease equation. Events were defined as new-onset stage III chronic kidney disease (CKD) or worsening of CKD stage in preexisting CKD. Kaplan-Meier event-free survival was assessed. Cox regression was performed to identify predictors of events. A total of 132 patients were analyzed, including 62 (47.0%) with hydronephrosis. Median follow up was 28.6 months. Patients with hydronephrosis had larger tumors (p = 0.045) and higher pathologic stage (p = 0.010) than those without hydronephrosis. Baseline eGFR was comparable between groups (p = 0.088). Patients without hydronephrosis experienced greater declines in eGFR following surgery (p < 0.001) and higher event rates at first (42.8% versus 24.2%, p = 0.028) and last (54.2% versus 30.6%, p = 0.008) follow up. On Cox regression, hydronephrosis predicted lower event likelihood in the long term (univariate HR 0.54, p = 0.033), while ureteral tumor location predicted lower event likelihood in the short term (HR 0.52, p = 0.030). Patients with hydronephrosis undergoing RNU for UTUC experience less decline in renal function than those without hydronephrosis. Given the prevalence of renal dysfunction in patients with UTUC, our results may help inform preoperative counseling.

To examine the effectiveness of a hospital-based nurse-led secondary prevention clinic.

PubMed

Mainie, Paula M; Moore, Gillian; Riddell, John W; Adgey, A A Jennifer

2005-12-01

Modification of cardiovascular risk factors can reduce the incidence of myocardial infarction (MI), effectively extend survival, decrease the need for interventional procedures, and improve quality of life in persons with known cardiovascular disease. Pharmacological treatments and important lifestyle changes reduce people's risks substantially (by 1/3 to 2/3) and can slow and perhaps reverse progression of established coronary disease. When used appropriately, these interventions are more cost-effective than many other treatments, currently provided by the National Health Service [Department of Health National Service Frameworks: coronary heart disease. Preventing coronary heart disease in high risk patients. 2000. HMSO.] Secondary prevention clinics are effective means by which to ensure targets are achieved and assist primary care in long-term maintenance of lifestyle change and drug optimisation. A 2-year hospital-based pilot project was established at the Royal Hospitals, April 2001-April 2003. The aim of the project was to target patients with coronary heart disease, post-MI and/or coronary artery bypass grafting and/or percutaneous coronary intervention, 6 months following their cardiac event. The plan was to assess patient risk factors and medication a minimum of 6 months following their cardiac event to ascertain if government targets were being achieved; secondly, to examine the effectiveness of a hospital-based nurse-led secondary prevention clinic on modifying risk factors and optimising drug therapies.

Inclusive jet production in ultrarelativistic proton-nucleus collisions

NASA Astrophysics Data System (ADS)

Perepelitsa, Dennis V.

High-pT processes in proton- and deuteron-nucleus collisions at TeV energies are the best presently available way to study the partonic structure of the nucleus in a high-density regime. Jet production over a wide range of phase space can significantly constrain the current knowledge of nuclear parton distribution functions (nPDFs), which are substantially less well understood than the corresponding PDFs in protons and which have only recently begun to be treated in a spatially-dependent way. An accurate knowledge of nPDFs is crucial for a definitive control of perturbative processes in a cold nuclear environment, since high-pT probes are used to quantitatively investigate the hot QCD matter created in ultrarelativistic nucleus-nucleus collisions. Furthermore, jets from low Bjorken-x partons can probe the transition from the dilute to saturated nuclear regimes. Jet production is investigated in d+Au collisions at √s = 200 GeV with the PHENIX detector at the Relativistic Heavy Ion Collider (RHIC), and in p+Pb collisions at √s = 5.02 TeV with the ATLAS detector at the Large Hadron Collider (LHC). The measurements shown here utilize ∫Ldt = 23 nb-1 and 0.2 pb-1 of 200 GeV d+Au and pp data, respectively, recorded in 2007-8 at RHIC and ∫Ldt = 31 nb -1 and 4.1 pb-1 of 5.02 TeV p+Pb and 2.76 TeV pp data, respectively, recorded in 2013 at the LHC. Jets are reconstructed using the sigma=0.3 Gaussian filter and R=0.4, 0.6 anti-kT algorithms. Inclusive, centrality-dependent jet yields within |eta| < 0.35 and 10 GeV < p T < 40 GeV in 200 GeV d+Au and pp collisions are presented. The jet yield in d+Au collisions relative to the geometric expectation is found to be slightly suppressed (≍0.9) in central events and moderately enhanced (≍1.3) in peripheral events, with no modification when averaged over all d+Au events. Separately, inclusive, centrality-dependent jet yields within |y *| < 4.4 and 25 GeV < pT < 800 GeV in 5.02 TeV p+Pb and 2.76 TeV pp collisions are presented. The event centrality in p+Pb collisions is determined by the sum of the transverse energy in the Pb-going forward calorimeter, SigmaETPb, and the mean number of participating nucleons < Npart > is estimated using the Glauber and Glauber-Gribov models of semiclassical p+A collisions. The jet yield in p+Pb collisions relative to the geometric expectation is found to be suppressed in central events and enhanced in peripheral events. The modifications are found to be stronger at higher- pT and at more forward (downstream proton) rapidities. Furthermore, it is observed that for each centrality selection, the modification at all rapidities is consistent with a simple function of the total jet energy only. The implications of the results are discussed, including a comparison of the modifications between RHIC and LHC energies.

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...

Genetic diversity-seeing the forest through the trees

Treesearch

M. Thompson Conkle

1992-01-01

Forest trees, populations, races, species, and taxonomic groups above the species level display rich variation in biochemical markers. The variation stems from inherited modifications that trace back in time, through converging ancestries, towards common progenitors. Past movements of continents, mountain building events, and climate changes isolated forest populations...

38 CFR 36.4315 - Loan modifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... all of the following conditions are met: (1) The loan is in default; (2) The event or circumstances...) All modified loans must bear a fixed-rate of interest, which may not exceed the Government National... position, such as homeowner association fees, special assessments, water and sewer liens, etc., may be...

ON THE MODIFICATION OF THE LOW FLOW-RATE PM10 DICHOTOMOUS SAMPLER INLET

EPA Science Inventory

A popular flat-topped inlet used for the collection of atmospheric particulate matter was modified to reduce water intrusion during rain and snow events. Simple alterations in the intake region of this inlet were made, including a larger drain hole, a one piece top plate, and ...

Drug development and manufacturing

DOEpatents

Warner, Benjamin P.; McCleskey, T. Mark; Burrell, Anthony K.

2015-10-13

X-ray fluorescence (XRF) spectrometry has been used for detecting binding events and measuring binding selectivities between chemicals and receptors. XRF may also be used for estimating the therapeutic index of a chemical, for estimating the binding selectivity of a chemical versus chemical analogs, for measuring post-translational modifications of proteins, and for drug manufacturing.

Problems in Aggression: Three Case Studies.

ERIC Educational Resources Information Center

Holt, Wilma J.

This paper reviews three studies which illustrate the use of two different techniques of behavior modification to control aggression in preschool children in classroom situations. The first technique demonstrated the use of "time-out" as a mild punishment procedure. The teacher changed events following aggression by briefly removing the child from…

76 FR 68017 - Federal Acquisition Regulation; Preventing Personal Conflicts of Interest for Contractor...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-02

... Contractor Employees Performing Acquisition Functions AGENCIES: Department of Defense (DoD), General Services... personal conflicts of interest by employees of Government contractors as required by statute. DATES... clause for future orders. In the event that a contractor refuses to accept such a modification, the...

Signal perception, transduction, and response in gravity resistance. Another graviresponse in plants

NASA Astrophysics Data System (ADS)

Hoson, T.; Saito, Y.; Soga, K.; Wakabayashi, K.

Resistance to the gravitational force is a serious problem that plants have had to solve to survive on land. Mechanical resistance to the pull of gravity is thus a principal graviresponse in plants, comparable to gravitropism. Nevertheless, only limited information has been obtained for this gravity response. We have examined the mechanism of gravity-induced mechanical resistance using hypergravity conditions produced by centrifugation. As a result, we have clarified the outline of the sequence of events leading to the development of mechanical resistance. The gravity signal may be perceived by mechanoreceptors (mechanosensitive ion channels) on the plasma membrane and it appears that amyloplast sedimentation in statocytes is not involved. Transformation and transduction of the perceived signal may be mediated by the structural or physiological continuum of microtubule-cell membrane-cell wall. As the final step in the development of mechanical resistance, plants construct a tough body by increasing cell wall rigidity. The increase in cell wall rigidity is brought about by modification of the metabolism of certain wall constituents and modification of the cell wall environment, especially pH. We need to clarify the details of each step by future space and ground-based experiments.

Mitochondrial Proteome Studies in Seeds during Germination

PubMed Central

Czarna, Malgorzata; Kolodziejczak, Marta; Janska, Hanna

2016-01-01

Seed germination is considered to be one of the most critical phases in the plant life cycle, establishing the next generation of a plant species. It is an energy-demanding process that requires functioning mitochondria. One of the earliest events of seed germination is progressive development of structurally simple and metabolically quiescent promitochondria into fully active and cristae-containing mitochondria, known as mitochondrial biogenesis. This is a complex and tightly regulated process, which is accompanied by sequential and dynamic gene expression, protein synthesis, and post-translational modifications. The aim of this review is to give a comprehensive summary of seed mitochondrial proteome studies during germination of various plant model organisms. We describe different gel-based and gel-free proteomic approaches used to characterize mitochondrial proteomes of germinating seeds as well as challenges and limitations of these proteomic studies. Furthermore, the dynamic changes in the abundance of the mitochondrial proteomes of germinating seeds are illustrated, highlighting numerous mitochondrial proteins involved in respiration, tricarboxycylic acid (TCA) cycle, metabolism, import, and stress response as potentially important for seed germination. We then review seed mitochondrial protein carbonylation, phosphorylation, and S-nitrosylation as well as discuss the possible link between these post-translational modifications (PTMs) and the regulation of seed germination. PMID:28248229

Targeting the Regulatory Machinery of BIM for Cancer Therapy

PubMed Central

Harada, Hisashi; Grant, Steven

2013-01-01

BIM represents a BH3-only proapoptotic member of the BCL-2 family of apoptotic regulatory proteins. Recent evidence suggests that in addition to its involvement in normal homeostasis, BIM plays a critical role in tumor cell biology, including the regulation of tumorigenesis through activities as a tumor suppressor, tumor metastasis, and tumor cell survival. Consequently, BIM has become the focus of intense interest as a potential target for cancer chemotherapy. The control of BIM expression is complex, and involves multiple factors, including epigenetic events (i.e., promoter acetylation or methylation, miRNA), transcription factors, posttranscriptional regulation, and posttranslational modifications, most notably phosphorylation. Significantly, the expression of BIM by tumor cells has been shown to play an important role in determining the response of transformed cells to not only conventional cytotoxic agents, but also to a broad array of targeted agents that interrupt cell signaling and survival pathways. Furthermore, modifications in BIM expression may be exploited to improve the therapeutic activity and potentially the selectivity of such agents. It is likely that evolving insights into the factors that regulate BIM expression will ultimately lead to novel BIM-based therapeutic strategies in the future. PMID:22856430

A cost minimisation and Bayesian inference model predicts startle reflex modulation across species.

PubMed

Bach, Dominik R

2015-04-07

In many species, rapid defensive reflexes are paramount to escaping acute danger. These reflexes are modulated by the state of the environment. This is exemplified in fear-potentiated startle, a more vigorous startle response during conditioned anticipation of an unrelated threatening event. Extant explanations of this phenomenon build on descriptive models of underlying psychological states, or neural processes. Yet, they fail to predict invigorated startle during reward anticipation and instructed attention, and do not explain why startle reflex modulation evolved. Here, we fill this lacuna by developing a normative cost minimisation model based on Bayesian optimality principles. This model predicts the observed pattern of startle modification by rewards, punishments, instructed attention, and several other states. Moreover, the mathematical formalism furnishes predictions that can be tested experimentally. Comparing the model with existing data suggests a specific neural implementation of the underlying computations which yields close approximations to the optimal solution under most circumstances. This analysis puts startle modification into the framework of Bayesian decision theory and predictive coding, and illustrates the importance of an adaptive perspective to interpret defensive behaviour across species. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

Walking and talking the tree of life: Why and how to teach about biodiversity

PubMed Central

Ballen, Cissy J.; Greene, Harry W.

2017-01-01

Taxonomic details of diversity are an essential scaffolding for biology education, yet outdated methods for teaching the tree of life (TOL), as implied by textbook content and usage, are still commonly employed. Here, we show that the traditional approach only vaguely represents evolutionary relationships, fails to denote major events in the history of life, and relies heavily on memorizing near-meaningless taxonomic ranks. Conversely, a clade-based strategy—focused on common ancestry, monophyletic groups, and derived functional traits—is explicitly based on Darwin’s “descent with modification,” provides students with a rational system for organizing the details of biodiversity, and readily lends itself to active learning techniques. We advocate for a phylogenetic classification that mirrors the TOL, a pedagogical format of increasingly complex but always hierarchical presentations, and the adoption of active learning technologies and tactics. PMID:28319149

Economic and Social Impact of Influenza Mitigation Strategies by Demographic Class

PubMed Central

Barrett, Chris; Bisset, Keith; Leidig, Jonathan; Marathe, Achla; Marathe, Madhav

2011-01-01

Background We aim to determine the economic and social impact of typical interventions proposed by the public health officials and preventive behavioral changes adopted by the private citizens in the event of a “flu-like” epidemic. Method We apply an individual-based simulation model to the New River Valley area of Virginia for addressing this critical problem. The economic costs include not only the loss in productivity due to sickness but also the indirect cost incurred through disease avoidance and caring for dependents. Results The results show that the most important factor responsible for preventing income loss is the modification of individual behavior; it drops the total income loss by 62% compared to the base case. The next most important factor is the closure of schools which reduces the total income loss by another 40%. Conclusions The preventive behavior of the private citizens is the most important factor in controlling the epidemic. PMID:21339828

DYn-2 Based Identification of Arabidopsis Sulfenomes*

PubMed Central

Akter, Salma; Huang, Jingjing; Bodra, Nandita; De Smet, Barbara; Wahni, Khadija; Rombaut, Debbie; Pauwels, Jarne; Gevaert, Kris; Carroll, Kate; Van Breusegem, Frank; Messens, Joris

2015-01-01

Identifying the sulfenylation state of stressed cells is emerging as a strategic approach for the detection of key reactive oxygen species signaling proteins. Here, we optimized an in vivo trapping method for cysteine sulfenic acids in hydrogen peroxide (H2O2) stressed plant cells using a dimedone based DYn-2 probe. We demonstrated that DYn-2 specifically detects sulfenylation events in an H2O2 dose- and time-dependent way. With mass spectrometry, we identified 226 sulfenylated proteins after H2O2 treatment of Arabidopsis cells, residing in the cytoplasm (123); plastid (68); mitochondria (14); nucleus (10); endoplasmic reticulum, Golgi and plasma membrane (7) and peroxisomes (4). Of these, 123 sulfenylated proteins have never been reported before to undergo cysteine oxidative post-translational modifications in plants. All in all, with this DYn-2 approach, we have identified new sulfenylated proteins, and gave a first glance on the locations of the sulfenomes of Arabidopsis thaliana. PMID:25693797

Reliable method for generating double-stranded DNA vectors containing site-specific base modifications.

PubMed

Brégeon, Damien; Doetsch, Paul W

2004-11-01

Cells of all living organisms are continuously exposed to physical and chemical agents that damage DNA and alter the integrity of their genomes. Despite the relatively high efficiency of the different repair pathways, some lesions remain in DNA when it is replicated or transcribed. Lesion bypass by DNA and RNA polymerases has been the subject of numerous investigations. However, knowledge of the in vivo mechanism of transcription lesion bypass is very limited because no robust methodology is available. Here we describe a protocol based on the synthesis of a complementary strand of a circular, single-stranded DNA molecule, which allows for the production of large amounts of double-stranded DNA containing a lesion at a specific position in a transcribed sequence. Such constructs can subsequently be used for lesion bypass studies in vivo by RNA polymerase and to ascertain how these events can be affected by the genetic background of the cells.

The molecular bases of the suicidal brain

PubMed Central

Turecki, Gustavo

2017-01-01

Suicide ranks among the leading causes of death around the world, and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors — such as familial and genetic predisposition, as well as early-life adversity — increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors associate with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes associated with suicidality, and presents some promising avenues for future research. PMID:25354482

Real-time landslide warning during heavy rainfall

USGS Publications Warehouse

Keefer, D.K.; Wilson, R.C.; Mark, R.K.; Brabb, E.E.; Brown, W. M.; Ellen, S.D.; Harp, E.L.; Wieczorek, G.F.; Alger, C.S.; Zatkin, R.S.

1987-01-01

A real-time system for issuing warnings of landslides during major storms is being developed for the San Francisco Bay region, California. The system is based on empirical and theoretical relations between rainfall and landslide initiation, geologic determination of areas susceptible to landslides, real-time monitoring of a regional network of telemetering rain gages, and National Weather Service precipitation forecasts. This system was used to issue warnings during the storms of 12 to 21 February 1986, which produced 800 millimeters of rainfall in the region. Although analysis after the storms suggests that modifications and additional developments are needed, the system successfully predicted the times of major landslide events. It could be used as a prototype for systems in other landslide-prone regions.

Physical activity, the Framingham risk score and risk of coronary heart disease in men and women of the EPIC-Norfolk study.

PubMed

Arsenault, Benoit J; Rana, Jamal S; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J; Kastelein, John J P; Boekholdt, S Matthijs; Khaw, Kay-Tee

2010-03-01

Test the hypothesis that considering leisure-time and work-related physical activity habits in addition to the Framingham risk score (FRS) would result into better classification of coronary heart disease (CHD) risk than FRS alone. Prospective, population-based study of 9564 men and 12165 women aged 45-79 years followed for an average of 11.4 years. A modified FRS which takes into account physical activity (evaluated using a validated lifestyle questionnaire taking into account leisure-time and work-related physical activity) was computed. During follow-up, 2191 CHD events occurred. Among 3369 men who were classified as intermediate risk (event rate of 12.4%) according to the FRS, 413 were reclassified into the low-risk category and 279 were reclassified into the high-risk category after modification of the FRS. After reclassification of these men, CHD event rate was of 5.3% and 18.6%, respectively for men classified at low and high CHD risk. Among 4766 women initially classified as intermediate risk (event rate of 8.4%), 1282 were reclassified into the low-risk category whereas 1071 women were reclassified into the high-risk category. After reclassification of these women, CHD event rate was of 6.8% and 12.2%, respectively for women classified at low and high CHD risk. Results of the present study suggest that asking simple questions about leisure-time and work-related physical activity which can be rapidly obtained by any physician at no cost could be helpful in the estimation of patients' CHD risk.

A brief histone in time: understanding the combinatorial functions of histone PTMs in the nucleosome context.

PubMed

Ng, Marlee K; Cheung, Peter

2016-02-01

It has been over 50 years since Allfrey et al. proposed that histone acetylation regulates RNA synthesis, and the study of histone modifications has progressed at an extraordinary pace for the past two decades. In this review, we provide a perspective on some key events and advances in our understanding of histone modifications. We also highlight reagents and tools from past to present that facilitated progress in this research field. Using histone H3 phosphorylation as an underlying thread, we review the rationale that led to the proposal of the histone code hypothesis, as well as examples that illustrate the concepts of combinatorial histone modifications and cross-talk pathways. We further highlight the importance of investigating these mechanisms in the context of nucleosomes rather than just at the histone level and present current and developing approaches for such studies. Overall, research on histone modifications has yielded great mechanistic insights into the regulation of genomic functions, and extending these studies using nucleosomes will further elucidate the complexity of these pathways in a more physiologically relevant context.

Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management.

PubMed

Petersen, John L; McGuire, Darren K

2005-02-01

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.

Evolution of Query Optimization Methods

NASA Astrophysics Data System (ADS)

Hameurlain, Abdelkader; Morvan, Franck

Query optimization is the most critical phase in query processing. In this paper, we try to describe synthetically the evolution of query optimization methods from uniprocessor relational database systems to data Grid systems through parallel, distributed and data integration systems. We point out a set of parameters to characterize and compare query optimization methods, mainly: (i) size of the search space, (ii) type of method (static or dynamic), (iii) modification types of execution plans (re-optimization or re-scheduling), (iv) level of modification (intra-operator and/or inter-operator), (v) type of event (estimation errors, delay, user preferences), and (vi) nature of decision-making (centralized or decentralized control).

Two damaging hydrogeological events in Calabria, September 2000 and November 2015. Comparative analysis of causes and effects

NASA Astrophysics Data System (ADS)

Petrucci, Olga; Caloiero, Tommaso; Aurora Pasqua, Angela

2016-04-01

Each year, especially during winter season, some episode of intense rain affects Calabria, the southernmost Italian peninsular region, triggering flash floods and mass movements that cause damage and fatalities. This work presents a comparative analysis between two events that affected the southeast sector of the region, in 2000 and 2014, respectively. The event occurred between 9th and 10th of September 2000 is known in Italy as Soverato event, after the name of the municipality where it reached the highest damage severity. In the Soverato area, more than 200 mm of rain that fell in 24 hours caused a disastrous flood that swept away a campsite at about 4 a.m., killing 13 people and hurting 45. Besides, the rain affected a larger area, causing damage in 89 (out of 409) municipalities of the region. Flooding was the most common process, which damaged housing and trading. Landslide mostly affected the road network, housing and cultivations. The most recent event affected the same regional sector between 30th October and 2nd November 2015. The daily rain recorded at some of the rain gauges of the area almost reached 400 mm. Out of the 409 municipalities of Calabria, 109 suffered damage. The most frequent types of processes were both flash floods and landslides. The most heavily damaged element was the road network: the representative picture of the event is a railway bridge destroyed by the river flow. Housing was damaged too, and 486 people were temporarily evacuated from home. The event also caused a victim killed by a flood. The event-centred study approach aims to highlight differences and similarities in both the causes and the effects of the two events that occurred at a temporal distance of 14 years. The comparative analysis focus on three main aspects: the intensity of triggering rain, the modifications of urbanised areas, and the evolution of emergency management. The comparative analysis of rain is made by comparing the return period of both daily and cumulative rain. The modifications of urbanised sectors is obtained by comparing ISTAT (National Statistic Institute of Italy) data and google maps of the affected areas at the time of the occurrence of the events. The emergency management is analysed by comparing the types and extend of civil protection alerts diffused in the two studied cases.

Audience-contingent variation in action demonstrations for humans and computers.

PubMed

Herberg, Jonathan S; Saylor, Megan M; Ratanaswasd, Palis; Levin, Daniel T; Wilkes, D Mitchell

2008-09-01

People may exhibit two kinds of modifications when demonstrating action for others: modifications to facilitate bottom-up, or sensory-based processing; and modifications to facilitate top-down, or knowledge-based processing. The current study examined actors' production of such modifications in action demonstrations for audiences that differed in their capacity for intentional reasoning. Actors' demonstrations of complex actions for a non-anthropomorphic computer system and for people (adult and toddler) were compared. Evidence was found for greater highlighting of top-down modifications in the demonstrations for the human audiences versus the computer audience. Conversely, participants highlighted simple perceptual modifications for the computer audience, producing more punctuated and wider ranging motions. This study suggests that people consider differences in their audiences when demonstrating action. 2008 Cognitive Science Society, Inc.

Modification of oral dosage forms for the older adult: An Irish prevalence study.

PubMed

Mc Gillicuddy, Aoife; Kelly, Maria; Sweeney, Catherine; Carmichael, Ann; Crean, Abina M; Sahm, Laura J

2016-08-20

Age-related pharmacological changes complicate oral dosage form (ODF) suitability for older adults. The aim of this study was to investigate the appropriateness of ODF for older adults by determining the prevalence of ODF modifications in an aged care facility in Ireland. Drug charts for eligible patients were obtained. Details of all medications administered were recorded. ODF modifications were examined to determine if they were evidence-based: defined as complying with the product license or best practice guidelines (BPG). In total, of 111 patients, 35.1% received at least one modified medicine. Medicines were most commonly modified to facilitate fractional dosing (82.0%). Of the 68 instances of medicine modification, 35.3% complied with the product license. Of the 44 unlicensed modifications, 14 complied with BPG. Therefore, 44.1% of modifications were not evidence-based. This study highlights that clinicians have to routinely tailor commercial ODF to meet older patients' needs despite the lack of an evidence-base for almost half of these modifications. The main factor contributing to these modifications is the lack of appropriate, licensed dosage forms. However, reimbursement policies also play a role. Research is needed to optimise medicine administration and to provide clinicians with much needed evidence to support their daily practice. Copyright © 2016 Elsevier B.V. All rights reserved.

The Modification of Diet in Renal Disease 4-calculated glomerular filtration rate is a better prognostic factor of cardiovascular events than classical cardiovascular risk factors in patients with peripheral arterial disease.

PubMed

Romero, Jose-María; Bover, Jordi; Fite, Joan; Bellmunt, Sergi; Dilmé, Jaime-Félix; Camacho, Mercedes; Vila, Luis; Escudero, Jose-Román

2012-11-01

Risk prediction is important in medical management, especially to optimize patient management before surgical intervention. No quantitative risk scores or predictors are available for patients with peripheral arterial disease (PAD). Surgical risk and prognosis are usually based on anesthetic scores or clinical evaluation. We suggest that renal function is a better predictor of risk than other cardiovascular parameters. This study used the four-variable Modification of Diet in Renal Disease (MDRD-4)-calculated glomerular filtration rate (GFR) to compare classical cardiovascular risk factors with prognosis and cardiovascular events of hospitalized PAD patients. The study evaluated 204 patients who were admitted for vascular intervention and diagnosed with grade IIb, III, or IV PAD or with carotid or renal stenosis. Those with carotid or renal stenosis were excluded, leaving 188 patients who were randomized from 2004 to 2005 and monitored until 2010. We performed a life-table analysis with a 6-year follow-up period and one final checkpoint. The following risk factors were evaluated: age, sex, ischemic heart disease, ictus (as a manifestation of cerebrovascular disease related to systemic arterial disease), diabetes, arterial hypertension, dyslipidemia, smoking, chronic obstructive pulmonary disease, type of vascular intervention, and urea and creatinine plasma levels. The GFR was calculated using the MDRD-4 equation. Death, major cardiovascular events, and reintervention for arterial disease were recorded during the follow-up. Patients (73% men) were a mean age of 71.38 ± 11.43 (standard deviation) years. PAD grade IIb was diagnosed in 41 (20%) and grade III-IV in 147 (72%). Forty-two minor amputations (20.6%), 21 major amputations (10.3%), and 102 revascularizations (50%) were performed. A major cardiovascular event occurred in 60 patients (29.4%), and 71 (34.8%) died. Multivariate logistic regression analysis showed that the MDRD-4 GFR, age, and male sex were independent variables related to death and that the MDRD-4 GFR and chronic obstructive pulmonary disease were related to major cardiovascular events. A statistically significant relationship was also found between serum creatinine levels and reintervention rates. The MDRD-4 GFR was a better predictor of risk of death or infarction than classical cardiovascular risk factors in patients with PAD. This suggests that its routine use in the initial evaluation in patients with PAD is beneficial. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Fingerprints of Modified RNA Bases from Deep Sequencing Profiles.

PubMed

Kietrys, Anna M; Velema, Willem A; Kool, Eric T

2017-11-29

Posttranscriptional modifications of RNA bases are not only found in many noncoding RNAs but have also recently been identified in coding (messenger) RNAs as well. They require complex and laborious methods to locate, and many still lack methods for localized detection. Here we test the ability of next-generation sequencing (NGS) to detect and distinguish between ten modified bases in synthetic RNAs. We compare ultradeep sequencing patterns of modified bases, including miscoding, insertions and deletions (indels), and truncations, to unmodified bases in the same contexts. The data show widely varied responses to modification, ranging from no response, to high levels of mutations, insertions, deletions, and truncations. The patterns are distinct for several of the modifications, and suggest the future use of ultradeep sequencing as a fingerprinting strategy for locating and identifying modifications in cellular RNAs.

Transgenerational epigenetic effects on animal behaviour.

PubMed

Jensen, Per

2013-12-01

Over the last decade a shift in paradigm has occurred with respect to the interaction between environment and genes. It is now clear that animal genomes are regulated to a large extent as a result of input from environmental events and experiences, which cause short- and long-term modifications in epigenetic markings of DNA and histones. In this review, the evidence that such epigenetic modifications can affect the behaviour of animals is explored, and whether such acquired behaviour alterations can transfer across generation borders. First, the mechanisms by which experiences cause epigenetic modifications are examined. This includes, for example, methylation of cytosine in CpG positions and acetylation of histones, and studies showing that this can be modified by early experiences. Secondly, the evidence that specific modifications in the epigenome can be the cause of behaviour variation is reviewed. Thirdly, the extent to which this phenotypically active epigenetic variants can be inherited either through the germline or through reoccurring environmental conditions is examined. A particularly interesting observation is that epigenetic modifications are often linked to stress, and may possibly be mediated by steroid effects. Finally, the idea that transgenerationally stable epigenetic variants may serve as substrates for natural selection is explored, and it is speculated that they may even predispose for directed, non-random mutations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Early Exposure to Traffic-Related Air Pollution, Respiratory Symptoms at 4 Years of Age, and Potential Effect Modification by Parental Allergy, Stressful Family Events, and Sex: A Prospective Follow-up Study of the PARIS Birth Cohort.

PubMed

Rancière, Fanny; Bougas, Nicolas; Viola, Malika; Momas, Isabelle

2017-04-01

The relation between traffic-related air pollution (TRAP) exposure and the incidence of asthma/allergy in preschool children has been widely studied, but results remain heterogeneous, possibly due to differences in methodology and susceptibility to TRAP. We aimed to study the relation of early TRAP exposure with the development of respiratory/allergic symptoms and asthma during preschool years, and to investigate parental allergy, "stressful" family events, and sex as possible effect modifiers. We examined data of 2,015 children from the PARIS birth cohort followed up with repeated questionnaires completed by parents until age 4 years. TRAP exposure in each child's first year of life was estimated by nitrogen oxides (NO x ) air dispersion modeling, taking into account both home and day care locations. Association between TRAP exposure and patterns of wheezing, dry night cough, and rhinitis symptoms was studied using multinomial logistic regression models adjusted for potential confounders. Effect modification by parental history of allergy, stressful family events, and sex was investigated. An interquartile range (26 μg/m 3 ) increase in NO x levels was associated with an increased odds ratio (OR) of persistent wheezing at 4 years (adjusted OR = 1.27; 95% confidence interval: 1.09, 1.47). TRAP exposure was positively associated with persistent wheeze, dry cough, and rhinitis symptoms among children with a parental allergy, those experiencing stressful family events, and boys, but not in children whose parents did not have allergies or experience stressful events, or in girls (all interaction p -values < 0.2). This study supports the hypothesis that not all preschool children are equal regarding TRAP health effects. Parental history of allergy, stressful family events, and male sex may increase their susceptibility to adverse respiratory effects of early TRAP exposure.

Antioxidant protection of LDL by physiological concentrations of 17 beta-estradiol. Requirement for estradiol modification.

PubMed

Shwaery, G T; Vita, J A; Keaney, J F

1997-03-18

Exposure to estrogens reduces the risk for coronary artery disease and associated clinical events; however, the mechanisms responsible for these observations are not clear. Supraphysiological levels of estrogens act as antioxidants in vitro, limiting oxidation of low-density lipoprotein (LDL), an event implicated in atherogenesis. We investigated the conditions under which physiological concentrations of 17 beta-estradiol (E2) inhibit oxidative modification of LDL. Plasma incubated with E2 (0.1 to 100 nmol/L) for 4 hours yielded LDL that demonstrated a dose-related increase in resistance to oxidation by Cu2+ as measured by conjugated diene formation. This effect was dependent on plasma, because incubation of isolated LDL with E2 at these concentrations in buffered saline produced no effect on Cu(2+)-mediated oxidation. Incubation of plasma with E2 had no effect on LDL alpha-tocopherol content or cholesteryl ester hydroperoxide formation during the 4-hour incubation. Plasma incubation with [3H]E2 was associated with dose-dependent association of 3H with LDL. High-performance liquid chromatographic analysis of LDL derived from plasma incubated with [3H]E2 indicated that the majority of the associated species were not detectable as authentic E2 but as nonpolar forms of E2 that were susceptible to base hydrolysis consistent with fatty acid esterification of E2. Plasma-mediated association of E2 and subsequent antioxidant protection was inhibited by 5,5'-dithiobis(2-nitrobenzoic acid), an inhibitor of plasma acyltransferase activity. Exposure of LDL to physiological levels of E2 in a plasma milieu is associated with enhanced resistance to Cu(2+)-mediated oxidation and incorporation of E2 derivatives into LDL. This antioxidant capacity may be another means by which E2 limits coronary artery disease in women.

Assigning Quantitative Function to Post-Translational Modifications Reveals Multiple Sites of Phosphorylation That Tune Yeast Pheromone Signaling Output

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

Pincus, David; Ryan, Christopher J.; Smith, Richard D.

2013-03-12

Cell signaling systems transmit information by post-­translationally modifying signaling proteins, often via phosphorylation. While thousands of sites of phosphorylation have been identified in proteomic studies, the vast majority of sites have no known function. Assigning functional roles to the catalog of uncharacterized phosphorylation sites is a key research challenge. Here we present a general approach to address this challenge and apply it to a prototypical signaling pathway, the pheromone response pathway in Saccharomyces cerevisiae. The pheromone pathway includes a mitogen activated protein kinase (MAPK) cascade activated by a G-­protein coupled receptor (GPCR). We used mass spectrometry-based proteomics to identify sitesmore » whose phosphorylation changed when the system was active, and evolutionary conservation to assign priority to a list of candidate MAPK regulatory sites. We made targeted alterations in those sites, and measured the effects of the mutations on pheromone pathway output in single cells. Our work identified six new sites that quantitatively tuned system output. We developed simple computational models to find system architectures that recapitulated the quantitative phenotypes of the mutants. Our results identify a number of regulated phosphorylation events that contribute to adjust the input-­output relationship of this model eukaryotic signaling system. We believe this combined approach constitutes a general means not only to reveal modification sites required to turn a pathway on and off, but also those required for more subtle quantitative effects that tune pathway output. Our results further suggest that relatively small quantitative influences from individual regulatory phosphorylation events endow signaling systems with plasticity that evolution may exploit to quantitatively tailor signaling outcomes.« less

Large-scale prediction of ADAR-mediated effective human A-to-I RNA editing.

PubMed

Yao, Li; Wang, Heming; Song, Yuanyuan; Dai, Zhen; Yu, Hao; Yin, Ming; Wang, Dongxu; Yang, Xin; Wang, Jinlin; Wang, Tiedong; Cao, Nan; Zhu, Jimin; Shen, Xizhong; Song, Guangqi; Zhao, Yicheng

2017-08-10

Adenosine-to-inosine (A-to-I) editing by adenosine deaminase acting on the RNA (ADAR) proteins is one of the most frequent modifications during post- and co-transcription. To facilitate the assignment of biological functions to specific editing sites, we designed an automatic online platform to annotate A-to-I RNA editing sites in pre-mRNA splicing signals, microRNAs (miRNAs) and miRNA target untranslated regions (3' UTRs) from human (Homo sapiens) high-throughput sequencing data and predict their effects based on large-scale bioinformatic analysis. After analysing plenty of previously reported RNA editing events and human normal tissues RNA high-seq data, >60 000 potentially effective RNA editing events on functional genes were found. The RNA Editing Plus platform is available for free at https://www.rnaeditplus.org/, and we believe our platform governing multiple optimized methods will improve further studies of A-to-I-induced editing post-transcriptional regulation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

New Orleans After Hurricane Katrina: An Unnatural Disaster?

NASA Astrophysics Data System (ADS)

McNamara, D.; Werner, B.; Kelso, A.

2005-12-01

Motivated by destruction in New Orleans following hurricane Katrina, we use a numerical model to explore how natural processes, economic development, hazard mitigation measures and policy decisions intertwine to produce long periods of quiescence punctuated by disasters of increasing magnitude. Physical, economic and policy dynamics are modeled on a grid representing the subsiding Mississippi Delta region surrounding New Orleans. Water flow and resulting sediment erosion and deposition are simulated in response to prescribed river floods and storms. Economic development operates on a limited number of commodities and services such as agricultural products, oil and chemical industries and port services, with investment and employment responding to both local conditions and global constraints. Development permitting, artificial levee construction and pumping are implemented by policy agents who weigh predicted economic benefits (tax revenue), mitigation costs and potential hazards. Economic risk is reduced by a combination of private insurance, federal flood insurance and disaster relief. With this model, we simulate the initiation and growth of New Orleans coupled with an increasing level of protection from a series of flooding events. Hazard mitigation filters out small magnitude events, but terrain and hydrological modifications amplify the impact of large events. In our model, "natural disasters" are the inevitable outcome of the mismatch between policy based on short-time-scale economic calculations and stochastic forcing by infrequent, high-magnitude flooding events. A comparison of the hazard mitigation response to river- and hurricane-induced flooding will be discussed. Supported by NSF Geology and Paleontology and the Andrew W Mellon Foundation.

Cardiovascular Outcomes after a Respiratory Tract Infection among Adults with Non-Cystic Fibrosis Bronchiectasis: A General Population-based Study.

PubMed

Navaratnam, Vidya; Root, Adrian A; Douglas, Ian; Smeeth, Liam; Hubbard, Richard B; Quint, Jennifer K

2018-03-01

Studies suggest that adults with bronchiectasis are at increased risk of cardiovascular comorbidities. We aimed to quantify the relative risk of incident cardiovascular events after a respiratory tract infection among adults with bronchiectasis. Using UK electronic primary care records, we conducted a within-person comparison using the self-controlled case series method. We calculated the relative risk of first-time cardiovascular events (either first myocardial infarction or stroke) after a respiratory tract infection compared with the individual's baseline risk. Our cohort consisted of 895 adult men and women with non-cystic fibrosis bronchiectasis with a first myocardial infarction or stroke and at least one respiratory tract infection. There was an increased rate of first-time cardiovascular events in the 91-day period after a respiratory tract infection (incidence rate ratio, 1.56; 95% confidence interval, 1.20-2.02). The rate of a first cardiovascular event was highest in the first 3 days after a respiratory tract infection (incidence rate ratio, 2.73; 95% confidence interval, 1.41-5.27). These data suggest that respiratory tract infections are strongly associated with a transient increased risk of first-time myocardial infarction or stroke among people with bronchiectasis. As respiratory tract infections are six times more common in people with bronchiectasis than the general population, the increased risk has a disproportionately greater impact in these individuals. These findings may have implications for including cardiovascular risk modifications in airway infection treatment pathways in this population.

Rehabilitation and education are underutilized for mild stroke and TIA sufferers.

PubMed

Faux, Steven G; Arora, Pooja; Shiner, Christine T; Thompson-Butel, Angelica G; Klein, Linda A

2018-06-01

Transient ischemic attack (TIA) and mild stroke represent a large proportion of cerebrovascular events, at high risk of being followed by recurrent, serious events. The importance of early education addressing risk management, secondary prevention and lifestyle modifications is the centerpiece of further stroke prevention. However, delivering education and rehabilitation to this population can be complex and challenging. Via synthesis of a narrative review and clinical experience, we explore the unique and inherent complexities of rehabilitation management and education provision for patients following mild stroke and TIA. A considerable proportion of TIA/mild stroke survivors have ongoing rehabilitation needs that are poorly addressed. The need for rehabilitation in these patients is often overlooked, and available assessment tools lack the sensitivity to identify common subtle impairments in cognition, mood, language and fatigue. Active and accessible education interventions need to be initiated early after the event, and integrated with ongoing rehabilitation management. Priority areas in need of future development in this field are highlighted and discussed. Implications for rehabilitation Survivors of mild stroke and TIA have ongoing unmet rehabilitation needs and require a unique approach to rehabilitation and education. Rehabilitation needs are difficult to assess and poorly addressed in this cohort, where available assessment tools lack the sensitivity required to identify subtle impairments. Education needs to be initiated early after the event and involve active engagement of the patient in order to improve stroke knowledge, mood and motivate adherence to lifestyle modifications and secondary prevention. Rehabilitation physicians are currently an underutilized resource, who should be more involved in the management of all patients following TIA or mild stroke.

The impact of teachers’ modifications of an evidenced-based HIV prevention intervention on program outcomes

PubMed Central

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2015-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade six students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers’ modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25% or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers’ level of implementation. We conclude that poorer student outcomes were associated with heavy modifications. PMID:26297497

The Impact of Teachers' Modifications of an Evidenced-Based HIV Prevention Intervention on Program Outcomes.

PubMed

Wang, Bo; Stanton, Bonita; Lunn, Sonja; Rolle, Glenda; Poitier, Maxwell; Adderley, Richard; Li, Xiaoming; Koci, Veronica; Deveaux, Lynette

2016-01-01

The degree to which evidence-based program outcomes are affected by modifications is a significant concern in the implementation of interventions. The ongoing national implementation of an evidence-based HIV prevention program targeting grade 6 students in The Bahamas [Focus on Youth in The Caribbean (FOYC)] offers an opportunity to explore factors associated with teachers' modification of FOYC lessons and to examine the impact of types and degrees of modifications on student outcomes. Data were collected in 2012 from 155 teachers and 3646 students in 77 government elementary schools. Results indicate that teachers taught 16 of 30 core activities, 24.5 of 46 total activities and 4.7 of 8 sessions. Over one-half of the teachers made modifications to FOYC core activities; one-fourth of the teachers modified 25 % or more core activities that they taught (heavily modified FOYC). Omitting core activities was the most common content modification, followed by lengthening FOYC lessons with reading, writing assignments or role-play games, and shortening core activities or adding educational videos. Mixed-effects modeling revealed that omitting core activities had negative impacts on all four student outcomes. Shortening core activities and adding videos into lessons had negative impacts on HIV/AIDS knowledge and/or intention to use condom protection. Heavy modifications (>1/4 core activities) were associated with diminished program effectiveness. Heavy modifications and omitting or shortening core activities were negatively related to teachers' level of implementation. We conclude that poorer student outcomes were associated with heavy modifications.

78 FR 53494 - Dam Safety Modifications at Cherokee, Fort Loudoun, Tellico, and Watts Bar Dams

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-29

... fundamental part of this mission was the construction and operation of an integrated system of dams and... by the Federal Emergency Management Agency, TVA prepares for the worst case flooding event in order... appropriate best management practices during all phases of construction and maintenance associated with the...

Glutaredoxin GrxC2 catalyzes the glutathionylation and inactivation of Arabidopsis BRI1-ASSOCIATED RECEPTOR-LIKE KINASE 1 (BAK1) in vitro

USDA-ARS?s Scientific Manuscript database

Reversible protein phosphorylation, catalyzed by protein kinases, is the most widely studied post-translational modification (PTM) both in terms of its occurrence and the regulatory consequences of phosphorylation events on phosphorylated proteins. In addition to reversible phosphorylation, many pro...

77 FR 13499 - Fenamiphos; Data Call-in Order for Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-07

... your identity or contact information unless you provide it in the body of your comment. If you send... electronically, EPA recommends that you include your name and other contact information in the body of your... timely fashion. Additional events that may be the basis for modification or revocation of fenamiphos...

Modifications of Basketball Equipment and Children's Performance.

ERIC Educational Resources Information Center

Benham, Tami

Although children are not miniature adults, they are often treated as such when participating in many youth sport activities. Young athletes, for example, are generally expected to participate in sporting events with equipment that has been designed for adults. What effect might scaling down such equipment have on the young child's performance?…

Mission Report: STS-4 Test Mission Simulates Operational Flight. President Terms Success Golden Spike in Space

NASA Technical Reports Server (NTRS)

1982-01-01

The fourth space shuttle flight is summarized. An onboard electrophoresis experiment is reviewed. Crew physiology, the first getaway special, a lightning survey, shuttle environment measurement, prelaunch weather conditions, loss of solid rocket boosters, modification of thermal test program, and other events are also reviewed.

47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

47 CFR 73.810 - Third adjacent channel complaint and license modification procedure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... LPFM station's remedial efforts. (d) In the event that the number of unresolved complaints plus the... interference is traceable to the LPFM station. (e) If the number of unresolved and disputed complaints exceeds...) BROADCAST RADIO SERVICES RADIO BROADCAST SERVICES Low Power FM Broadcast Stations (LPFM) § 73.810 Third...

Cancer Progenitor Cells: The Result of an Epigenetic Event?

PubMed

Lapinska, Karolina; Faria, Gabriela; McGonagle, Sandra; Macumber, Kate Morgan; Heerboth, Sarah; Sarkar, Sibaji

2018-01-01

The concept of cancer stem cells was proposed in the late 1990s. Although initially the idea seemed controversial, the existence of cancer stem cells is now well established. However, the process leading to the formation of cancer stem cells is still not clear and thus requires further research. This article discusses epigenetic events that possibly produce cancer progenitor cells from predisposed cells by the influence of their environment. Every somatic cell possesses an epigenetic signature in terms of histone modifications and DNA methylation, which are obtained during lineage-specific differentiation of pluripotent stem cells, which is specific to that particular tissue. We call this signature an epigenetic switch. The epigenetic switch is not fixed. Our epigenome alters with aging. However, depending on the predisposition of the cells of a particular tissue and their microenvironment, the balance of the switch (histone modifications and the DNA methylation) may be tilted to immortality in a few cells, which generates cancer progenitor cells. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Epigenetic regulation of bud dormancy events in perennial plants

PubMed Central

Ríos, Gabino; Leida, Carmen; Conejero, Ana; Badenes, María Luisa

2014-01-01

Release of bud dormancy in perennial plants resembles vernalization in Arabidopsis thaliana and cereals. In both cases, a certain period of chilling is required for accomplishing the reproductive phase, and several transcription factors with the MADS-box domain perform a central regulatory role in these processes. The expression of DORMANCY-ASSOCIATED MADS-box (DAM)-related genes has been found to be up-regulated in dormant buds of numerous plant species, such as poplar, raspberry, leafy spurge, blackcurrant, Japanese apricot, and peach. Moreover, functional evidence suggests the involvement of DAM genes in the regulation of seasonal dormancy in peach. Recent findings highlight the presence of genome-wide epigenetic modifications related to dormancy events, and more specifically the epigenetic regulation of DAM-related genes in a similar way to FLOWERING LOCUS C, a key integrator of vernalization effectors on flowering initiation in Arabidopsis. We revise the most relevant molecular and genomic contributions in the field of bud dormancy, and discuss the increasing evidence for chromatin modification involvement in the epigenetic regulation of seasonal dormancy cycles in perennial plants. PMID:24917873

Engineered/designer biochar for contaminant removal/immobilization from soil and water: Potential and implication of biochar modification.

PubMed

Rajapaksha, Anushka Upamali; Chen, Season S; Tsang, Daniel C W; Zhang, Ming; Vithanage, Meththika; Mandal, Sanchita; Gao, Bin; Bolan, Nanthi S; Ok, Yong Sik

2016-04-01

The use of biochar has been suggested as a means of remediating contaminated soil and water. The practical applications of conventional biochar for contaminant immobilization and removal however need further improvements. Hence, recent attention has focused on modification of biochar with novel structures and surface properties in order to improve its remediation efficacy and environmental benefits. Engineered/designer biochars are commonly used terms to indicate application-oriented, outcome-based biochar modification or synthesis. In recent years, biochar modifications involving various methods such as, acid treatment, base treatment, amination, surfactant modification, impregnation of mineral sorbents, steam activation and magnetic modification have been widely studied. This review summarizes and evaluates biochar modification methods, corresponding mechanisms, and their benefits for contaminant management in soil and water. Applicability and performance of modification methods depend on the type of contaminants (i.e., inorganic/organic, anionic/cationic, hydrophilic/hydrophobic, polar/non-polar), environmental conditions, remediation goals, and land use purpose. In general, modification to produce engineered/designer biochar is likely to enhance the sorption capacity of biochar and its potential applications for environmental remediation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of oxidative DNA damage promoted by storage in sperm from sex-reversed rainbow trout.

PubMed

Pérez-Cerezales, S; Martínez-Páramo, S; Cabrita, E; Martínez-Pastor, F; de Paz, P; Herráez, M P

2009-03-01

Short-term storage and cryopreservation of sperm are two common procedures in aquaculture, used for routine practices in artificial insemination reproduction and gene banking, respectively. Nevertheless, both procedures cause injuries affecting sperm motility, viability, cell structure and DNA stability, which diminish reproductive success. DNA modification is considered extremely important, especially when sperm storage is carried out with gene banking purposes. DNA damage caused by sperm storage is not well characterized and previous studies have reported simple and double strand breaks that have been attributed to oxidative events promoted by the generation of free radicals during storage. The objective of this study was to reveal DNA fragmentation and to explore the presence of oxidized bases that could be produced by oxidative events during short-term storage and cryopreservation in sex-reversed rainbow trout (Oncorhynchus mykiss) spermatozoa. Sperm from six males was analyzed separately. Different aliquots of the samples were stored 2h (fresh) or 5 days at 4 degrees C or were cryopreserved. Then spermatozoa were analyzed using the Comet assay, as well as combining this method with digestion with two endonucleases from Escherichia coli (Endonuclease III, that cut in oxidized cytosines, and FPG, cutting in oxidized guanosines). Both storage procedures yielded DNA fragmentation, but only short-term storage oxidative events were clearly detected, showing that oxidative processes affect guanosines rather than cytosines. Cryopreservation increases DNA fragmentation but the presence of oxidized bases was not noticed, suggesting that mechanisms other than oxidative stress could be involved in DNA fragmentation promoted by freezing.

Stressful life events and cognitive decline in late life: moderation by education and age. The Cache County Study.

PubMed

Tschanz, Joann T; Pfister, Roxane; Wanzek, Joseph; Corcoran, Chris; Smith, Ken; Tschanz, Brian T; Steffens, David C; Østbye, Truls; Welsh-Bohmer, Kathleen A; Norton, Maria C

2013-08-01

Stressful life events (SLE) have been associated with increased dementia risk, but their association with cognitive decline has been inconsistent. In a longitudinal population-based study of older individuals, we examined the association between SLE and cognitive decline, and the role of potential effect modifiers. A total of 2665 non-demented participants of the Cache County Memory Study completed an SLE questionnaire at Wave 2 and were revisited 4 and 7 years later. The events were represented via several scores: total number, subjective rating (negative, positive, and unexpected), and a weighted summary based on their impact. Cognition was assessed at each visit with the modified Mini-Mental State Exam. General linear models were used to examine the association between SLE scores and cognition. Effect modification by age, education, and APOE genotype was tested. Years of formal education (p = 0.006) modified the effect of number of SLE, and age (p = 0.009) modified the effect of negative SLE on the rate of cognitive decline. Faster decline was observed among those with fewer years of education experiencing more SLE and also among younger participants experiencing more negative SLE. There was no association between other indicators of SLE and cognitive decline. APOE genotype did not modify any of the aforementioned associations. The effects of SLE on cognition in late life are complex and vary by individual factors such as age and education. These results may explain some of the contradictory findings in the literature. Copyright © 2012 John Wiley & Sons, Ltd.

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.

River channel sensitivity to change in the context of human activities and natural factors: an 80-year record of channel morphodynamics on the lower Santa Clara River, Ventura County, California

NASA Astrophysics Data System (ADS)

Downs, P. W.; Dusterhoff, S. R.; Sears, W. A.

2010-12-01

River channel adjustments arise from the application of numerous catchment-based stressors operating at different space and time scales. Natural stressors include the impact of climatic phenomena and their inheritance; human stressors include both direct and indirect factors whose impacts have grown in magnitude and intensity during the Anthropocene, especially since about 1945. Consequently, the sensitivity of river channel morphodynamics is likely to have changed also, with implications for landform understanding and river management. Reconstructing channel morphodynamics during the Anthropocene requires interpreting multiple historical and secondary data sources to document changes at sufficient (i.e., reach-scale) resolution: for the 60-km lower Santa Clara River (LSCR), Ventura County, California, we used flow, sediment and precipitation records, repeat aerial photographs, LiDAR data, repeat topographic surveys, in-channel vegetation data, field observations, numerical modeling of high flow events, and narrative accounts. The catchment historical context since European-American settlement includes periods dominated by ranching and colonization (ca.1820-1890), irrigations and diversions (ca.1890-1955), dams and river modifications (1955-1990), and urban population growth (1990-present). Natural stressors were investigated based on the correlation of instantaneous flood peaks with annual rainfall records in this semi-arid setting. Successful prediction of the majority of gauged floods since about 1950 allows a flood sequence to be reconstructed back to 1873. Floods are clustered and of considerably greater magnitude in El Nino years of the El Nino-Southern Oscillation. The great majority of sediment transport thus occurs in El Nino years so that the dominant discharge is the largest discharge on record, in contrast to humid-region alluvial rivers. Responding to these stressors, the average width of the active channel bed has become narrower by almost 50% (1938-2005), with downstream reaches losing their responsiveness to flood events over time, in contrast to the middle reaches. The channel bed has incised on average 0.7 m from 1949-2005, again with a strong contrast between the downstream reaches (average incision 2.4 m) and middle reaches (no incision). Overall, catchment historical disturbances to the LSCR consist of numerous ‘pulse’ disturbances related to sediment delivery during clustered flood events, and following wildfire and earthquakes, at least five human-caused ‘press’ disturbances and two human ‘pulse’ disturbances. The end product includes several ‘natural’ reaches that are highly responsive but resilient to flood events, and numerous disequilibrium lower reaches disconnected from this floodplain and with high potential sensitivity held in check by force. Long-term approaches to hazard management should consider vulnerability modification approaches.

Genomic and Epigenomic Alterations in Cancer.

PubMed

Chakravarthi, Balabhadrapatruni V S K; Nepal, Saroj; Varambally, Sooryanarayana

2016-07-01

Multiple genetic and epigenetic events characterize tumor progression and define the identity of the tumors. Advances in high-throughput technologies, like gene expression profiling, next-generation sequencing, proteomics, and metabolomics, have enabled detailed molecular characterization of various tumors. The integration and analyses of these high-throughput data have unraveled many novel molecular aberrations and network alterations in tumors. These molecular alterations include multiple cancer-driving mutations, gene fusions, amplification, deletion, and post-translational modifications, among others. Many of these genomic events are being used in cancer diagnosis, whereas others are therapeutically targeted with small-molecule inhibitors. Multiple genes/enzymes that play a role in DNA and histone modifications are also altered in various cancers, changing the epigenomic landscape during cancer initiation and progression. Apart from protein-coding genes, studies are uncovering the critical regulatory roles played by noncoding RNAs and noncoding regions of the genome during cancer progression. Many of these genomic and epigenetic events function in tandem to drive tumor development and metastasis. Concurrent advances in genome-modulating technologies, like gene silencing and genome editing, are providing ability to understand in detail the process of cancer initiation, progression, and signaling as well as opening up avenues for therapeutic targeting. In this review, we discuss some of the recent advances in cancer genomic and epigenomic research. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Efficacy and safety of sorafenib for advanced renal cell carcinoma: real-world data of patients with renal impairment.

PubMed

Tatsugami, Katsunori; Oya, Mototsugu; Kabu, Koki; Akaza, Hideyuki

2018-04-10

We retrospectively analysed the efficacy and safety of sorafenib in patients with advanced renal cell carcinoma with renal impairment. Patients were divided into two groups by an estimated glomerular filtration rate (eGFR) cut-off of 45 mL/min/1.73 m 2 . Background factors considered to affect prognosis were well balanced by propensity score matching between the groups. Demographics, dose modification, adverse events, tumour response, progression-free survival, and renal function (eGFR) were evaluated. Among 935 and 2008 patients with an eGFR of <45 and ≥45, respectively, 613 pairs were matched. The mean starting dose was significantly lower in patients with an eGFR of <45; however, the mean daily dose, median treatment duration, progression-free survival, and tumour response were similar between the groups. In terms of safety, no significant differences were found in serious adverse events, although cytopaenia (16.6% vs 10.6%) and renal dysfunction (4.4% vs 0.7%) were higher in patients with an eGFR of <45 than ≥45 in all adverse events. There were also no differences in dose modification, including dose reduction, dose interruption, and treatment discontinuation. Throughout the 12-month observation period, sorafenib in patients with an eGFR of <45 and ≥45 showed similar safety and efficacy, and treatment was continued without affecting renal function.

Mass spectrometry-based carboxyl footprinting of proteins: Method evaluation

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

Zhang, Hao; Wen, Jianzhong; Huang, Richard Y-C.

2012-02-01

Protein structure determines function in biology, and a variety of approaches have been employed to obtain structural information about proteins. Mass spectrometry-based protein footprinting is one fast-growing approach. One labeling-based footprinting approach is the use of a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and glycine ethyl ester (GEE) to modify solvent-accessible carboxyl groups on glutamate (E) and aspartate (D). This paper describes method development of carboxyl-group modification in protein footprinting. The modification protocol was evaluated by using the protein calmodulin as a model. Because carboxyl-group modification is a slow reaction relative to protein folding and unfolding, there is an issue that modificationsmore » at certain sites may induce protein unfolding and lead to additional modification at sites that are not solvent-accessible in the wild-type protein. We investigated this possibility by using hydrogen deuterium amide exchange (H/DX). The study demonstrated that application of carboxyl group modification in probing conformational changes in calmodulin induced by Ca{sup 2+} binding provides useful information that is not compromised by modification-induced protein unfolding.« less

Upper gastrointestinal issues in athletes.

PubMed

Waterman, Jason J; Kapur, Rahul

2012-01-01

Gastrointestinal (GI) complaints are common among athletes with rates in the range of 30% to 70%. Both the intensity of sport and the type of sporting activity have been shown to be contributing factors in the development of GI symptoms. Three important factors have been postulated as contributing to the pathophysiology of GI complaints in athletes: mechanical forces, altered GI blood flow, and neuroendocrine changes. As a result of those factors, gastroesophageal reflux disease (GERD), nausea, vomiting, gastritis, peptic ulcers, GI bleeding, or exercise-related transient abdominal pain (ETAP) may develop. GERD may be treated with changes in eating habits, lifestyle modifications, and training modifications. Nausea and vomiting may respond to simple training modifications, including no solid food 3 hours prior to an athletic event. Mechanical trauma, decreased splanchnic blood flow during exercise, and non-steroidal anti-inflammatory drugs (NSAID) contribute to gastritis, GI bleeding, and ulcer formation in athletes. Acid suppression with proton-pump inhibitors may be useful in athletes with persistence of any of the above symptoms. ETAP is a common, poorly-understood, self-limited acute abdominal pain which is difficult to treat. ETAP incidence increases in athletes beginning a new exercise program or increasing the intensity of their current exercise program. ETAP may respond to changes in breathing patterns or may resolve simply with continued training. Evaluation of the athlete with upper GI symptoms requires a thorough history, a detailed training log, a focused physical examination aimed at ruling out potentially serious causes of symptoms, and follow-up laboratory testing based on concerning physical examination findings.

Kidney Function and Cardiovascular Events in Postmenopausal Women: The Impact of Race and Ethnicity in the Women’s Health Initiative

PubMed Central

Arce, Cristina M.; Rhee, Jinnie J.; Cheung, Katharine L.; Hedlin, Haley; Kapphahn, Kristopher; Franceschini, Nora; Kalil, Roberto S.; Martin, Lisa W.; Qi, Lihong; Shara, Nawar M.; Desai, Manisha; Stefanick, Marcia L.; Winkelmayer, Wolfgang C.

2015-01-01

Background Kidney disease disproportionately affects minority populations including African Americans and Hispanics; therefore, understanding the relationship of kidney function to cardiovascular (CV) outcomes within different racial/ethnic groups is of considerable interest. We investigated the relationship between kidney function and CV events and assessed effect modification by race/ethnicity in the Women’s Health Initiative. Study Design Prospective cohort study Setting & Participants Baseline serum creatinine concentrations (assay traceable to isotope-dilution mass spectrometry standard) of 19,411 postmenopausal women aged 50–79 years who self-identified as either non-Hispanic white (n=8921), African American (n=7436), or Hispanic (n=3054) were used to calculate estimated glomerular filtration rates (eGFRs). Predictors Categories of eGFR (exposure); race/ethnicity (effect modifier). Outcomes The primary outcome was the composite of three physician-adjudicated CV events: myocardial infarction (MI), stroke, or CV-related death. Measurements We evaluated the multivariable-adjusted associations between categories of eGFR and CV events using proportional hazards regression and formally tested for effect modification by race/ethnicity. Results Over a mean follow-up of 7.6 years, 1424 CV events (653 MI, 627 strokes, 297 CV-related deaths) were observed. The association between eGFR and CV events was curvilinear; however, the association of eGFR with CV outcomes differed by race (P=0.006). In stratified analyses, we observed that the U-shaped association was present in non-Hispanic whites, whereas African American participants had a rather curvilinear relationship with lower eGFR being associated with higher CV risk and higher eGFR with reduced CV risk. Analyses among Hispanic women were inconclusive owing to few Hispanic women having very low or high eGFR and very few events occurring in these categories. Limitations Lack of urinary albumin measurements; residual confounding by unmeasured or imprecisely measured characteristics. Conclusions In postmenopausal women, the patterns of association between eGFR and CV risk differed between non-Hispanic whites and African American women. PMID:26337132

Renal function assessment in atrial fibrillation: Usefulness of chronic kidney disease epidemiology collaboration vs re-expressed 4 variable modification of diet in renal disease.

PubMed

Abumuaileq, Rami Riziq-Yousef; Abu-Assi, Emad; López-López, Andrea; Raposeiras-Roubin, Sergio; Rodríguez-Mañero, Moisés; Martínez-Sande, Luis; García-Seara, Francisco Javier; Fernandez-López, Xesus Alberte; González-Juanatey, Jose Ramón

2015-10-26

To compare the performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation. We studied 911 consecutive patients with non-valvular atrial fibrillation on vitamin-K antagonist. The performance of the re-expressed Modification of Diet in Renal Disease equation vs the new Chronic Kidney Disease Epidemiology Collaboration equation in patients with non-valvular atrial fibrillation with respect to either a composite endpoint of major bleeding, thromboembolic events and all-cause mortality or each individual component of the composite endpoint was assessed using continuous and categorical ≥ 60, 59-30, and < 30 mL/min per 1.73 m(2) estimated glomerular filtration rate. During 10 ± 3 mo, the composite endpoint occurred in 98 (10.8%) patients: 30 patients developed major bleeding, 18 had thromboembolic events, and 60 died. The new equation provided lower prevalence of renal dysfunction < 60 mL/min per 1.73 m(2) (32.9%), compared with the re-expressed equation (34.1%). Estimated glomerular filtration rate from both equations was independent predictor of composite endpoint (HR = 0.98 and 0.97 for the re-expressed and the new equation, respectively; P < 0.0001) and all-cause mortality (HR = 0.98 for both equations, P < 0.01). Strong association with thromboembolic events was observed only when estimated glomerular filtration rate was < 30 mL/min per 1.73 m(2): HR is 5.1 for the re-expressed equation, and HR = 5.0 for the new equation. No significant association with major bleeding was observed for both equations. The new equation reduced the prevalence of renal dysfunction. Both equations performed similarly in predicting major adverse outcomes.

Oxidative tryptophan modification by terpene- and squalene-hydroperoxides and a possible link to cross-reactions in diagnostic tests.

PubMed

Natsch, Andreas; Emter, Roger; Badertscher, Remo P; Brunner, Gerhard; Granier, Thierry; Kern, Susanne; Ellis, Graham

2015-06-15

Hydroperoxides can act as specific haptens and oxidatively modify proteins. Terpene hydroperoxides trigger unusually high frequencies of positive skin reactions in human patients if tested at high concentrations. It is unknown whether this is due to specific hapten formation. Here, we show that both terpene hydroperoxides and the endogenous hydroperoxide formed from squalene can oxidatively modify tryptophan. Oxidative modifications of Trp were recently postulated to explain cross-sensitization between unrelated photosensitizers. Current observations may extend this hypothesis: Oxidative events triggered by endogenous hydroperoxides and hydroperoxides/oxidants derived from xenobiotics might lead to a sensitized state detected by patch tests with high concentrations of hydroperoxides.

Investigation of surface halide modification of nitrile butadiene rubber

NASA Astrophysics Data System (ADS)

Sukhareva, K. V.; Mikhailov, I. A.; Andriasyan, Yu O.; Mastalygina, E. E.; Popov, A. A.

2017-12-01

The investigation is devoted to the novel technology of surface halide modification of rubber samples based on nitrile butadiene rubber (NBR). 1,1,2-trifluoro-1,2,2-trichlorethane was used as halide modifier. The developed technology is characterized by production stages reduction to one by means of treating the rubber compound with a halide modifier. The surface halide modification of compounds based on nitrile butadiene rubber (NBR) was determined to result in increase of resistance to thermal oxidation and aggressive media. The conducted research revealed the influence of modification time on chemical resistance and physical-mechanical properties of rubbers under investigation.

Histone modification: cause or cog?

PubMed

Henikoff, Steven; Shilatifard, Ali

2011-10-01

Histone modifications are key components of chromatin packaging but whether they constitute a 'code' has been contested. We believe that the central issue is causality: are histone modifications responsible for differences between chromatin states, or are differences in modifications mostly consequences of dynamic processes, such as transcription and nucleosome remodeling? We find that inferences of causality are often based on correlation and that patterns of some key histone modifications are more easily explained as consequences of nucleosome disruption in the presence of histone modifying enzymes. We suggest that the 35-year-old DNA accessibility paradigm provides a mechanistically sound basis for understanding the role of nucleosomes in gene regulation and epigenetic inheritance. Based on this view, histone modifications and variants contribute to diversification of a chromatin landscape shaped by dynamic processes that are driven primarily by transcription and nucleosome remodeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Tuned Single Parameter for Representing Conjunction Risk

NASA Technical Reports Server (NTRS)

Plakaloic, D.; Hejduk, M. D.; Frigm, R. C.; Newman, L. K.

2011-01-01

Satellite conjunction assessment risk analysis is a subjective enterprise that can benefit from quantitative aids and, to this end, NASA/GSFC has developed a fuzzy logic construct - called the F-value - to attempt to provide a statement of conjunction risk that amalgamates multiple indices and yields a more stable intra-event assessment. This construct has now sustained an extended tuning procedure against heuristic analyst assessment of event risk. The tuning effort has resulted in modifications to the calculation procedure and the adjustment of tuning coefficients, producing a construct with both more predictive force and a better statement of its error.

Asian Women's Action for Resilience and Empowerment Intervention: Stage I Pilot Study.

PubMed

Hahm, Hyeouk Chris; Chang, Stephanie Tzu-Han; Lee, Gloria Yoonseung; Tagerman, Michelle D; Lee, Christina S; Trentadue, Mia Pamela; Hien, Denise A

2017-01-01

This study describes the development and pilot test of Asian Women's Action for Resilience and Empowerment (AWARE), a culturally informed group psychotherapy intervention designed to reduce depressive symptoms, suicidality, substance use, and HIV and sexual risk behaviors among 1.5 and second generation Asian American (AA) women. To participate, AA women had to meet the criteria for posttraumatic stress disorder (PTSD) or have a history of exposure to interpersonal violence (IPV) as determined using the Clinician-Administered PTSD Scale (CAPS) and Traumatic Life Events Questionnaire (TLEQ). This article also presents the preliminary feasibility and acceptability of AWARE from its Stage I pilot study of nine Chinese, Korean, and Vietnamese American women. To foster holistic treatment, AWARE was developed based on original research findings from Stage 0 and integrated theoretical models including fractured identity theory, empowerment theory, cognitive behavioral therapy (CBT), mindfulness-based techniques, and the AIDS Risk Reduction Model (ARRM). The development of AWARE was an iterative process informed by participant feedback, which led to frequent intervention modifications for a future randomized controlled trial (RCT) in Stage II. A qualitative analysis of participant feedback informed the following modifications: further exploration of feelings, improvements in technology delivery, learning and practicing coping skills, more specific cultural tailoring related to sexual health, decreased number of sessions and increased time per session. Findings provide support for the acceptability and feasibility of AWARE as "culturally informed" for AA young women with IPV histories, high-risk behaviors, and mental health issues.

Financing biotechnology projects: lender due diligence requirements and the role of independent technical consultants.

PubMed

Keller, J B; Plath, P B

1999-01-01

An increasing number of biotechnology projects are being brought to commercialization using conventional structured finance sources, which have traditionally only been available to proven technologies and primary industries. Attracting and securing competitive cost financing from mainstream lenders, however, will require the sponsor of a new technology or process to undergo a greater level of due diligence. The specific areas and intensity of investigation, which are typically required by lenders in order to secure long-term financing for biotechnology-based manufacturing systems, is reviewed. The processes for evaluating the adequacy of prior laboratory testing and pilot plant demonstrations is discussed. Particular emphasis is given to scale-up considerations and the ability of the proposed facility design to accommodate significant modifications, in the event that scale-up problems are encountered.

Muon Simulation at the Daya Bay SIte

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

Mengyun, Guan; Jun, Cao; Changgen, Yang

2006-05-23

With a pretty good-resolution mountain profile, we simulated the underground muon background at the Daya Bay site. To get the sea-level muon flux parameterization, a modification to the standard Gaisser's formula was introduced according to the world muon data. MUSIC code was used to transport muon through the mountain rock. To deploy the simulation, first we generate a statistic sample of sea-level muon events according to the sea-level muon flux distribution formula; then calculate the slant depth of muon passing through the mountain using an interpolation method based on the digitized data of the mountain; finally transport muons through rockmore » to get underground muon sample, from which we can get results of muon flux, mean energy, energy distribution and angular distribution.« less

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment.

PubMed

McLean, Leon P; Cross, Raymond K

2014-03-01

Crohn's disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered.

Adverse events in IBD: to stop or continue immune suppressant and biologic treatment

PubMed Central

McLean, Leon P; Cross, Raymond K

2014-01-01

Crohn’s disease and ulcerative colitis affect an increasing number of patients. A variety of medical options exist for the treatment of these diseases including immune suppressants and biologic therapies. Unfortunately, these agents are associated with adverse events ranging from mild nuisance symptoms to potentially life-threatening complications including infections and malignancies. This review discusses adverse events associated with azathioprine, mercaptopurine, and methotrexate as well as anti-TNF-α and anti-integrin antibodies. In addition, adverse events associated with combination therapy are discussed as are clinical scenarios in which it may be reasonable to discontinue or de-escalate drug therapy. It is the responsibility of the treating gastroenterologist to effectively communicate the benefits and risks of therapy with patients; this review offers strategies that may assist providers in communicating risk with patients in addition to offering our perspective on whether modification or cessation of therapy can be considered. PMID:24490595

Major Life Events as Potential Triggers of Sudden Cardiac Arrest

PubMed Central

Wicks, April F; Lumley, Thomas; Lemaitre, Rozenn N; Sotoodehnia, Nona; Rea, Thomas D; McKnight, Barbara; Strogatz, David S; Bovbjerg, Viktor E; Siscovick, David S

2012-01-01

Background We investigated recent loss of or separation from afamily member or friend and risk of sudden cardiac arrest. Methods Our case-crossover study included 490 apparently-healthy married residents of King County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We compared exposure to spouse-reported family/friend events occurring ≤ 1 month before sudden cardiac arrest with events occurring n the previous 5 months. We evaluated potential effect modification by habitual vigorous physical activity. Results Recent family/friend events were associated with a higher risk of sudden cardiac arrest (odds ratio (OR) = 1.6 [95% confidence interval (CI) = 1.1-2.4]). ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6-2.2) and 2.0 (1.2-3.1), respectively, (interaction P = 0.02). Conclusions These results suggest family/friend events may trigger sudden cardiac arrest and raise the hypothesis that habitual vigorous physical activity may lower susceptibility to these potential triggers. PMID:22415111

Major life events as potential triggers of sudden cardiac arrest.

PubMed

Wicks, April F; Lumley, Thomas; Lemaitre, Rozenn N; Sotoodehnia, Nona; Rea, Thomas D; McKnight, Barbara; Strogatz, David S; Bovbjerg, Viktor E; Siscovick, David S

2012-05-01

We investigated the risk of sudden cardiac arrest in association with the recent loss of, or separation from, a family member or friend. Our case-crossover study included 490 apparently healthy married residents of King County, Washington, who suffered sudden cardiac arrest between 1988 and 2005. We compared exposure to spouse-reported family/friend events occurring ≤ 1 month before sudden cardiac arrest with events occurring in the previous 5 months. We evaluated potential effect modification by habitual vigorous physical activity. Recent family/friend events were associated with a higher risk of sudden cardiac arrest (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1-2.4). ORs for cases with and without habitual vigorous physical activity were 1.1 (0.6-2.2) and 2.0 (1.2-3.1), respectively (interaction P = 0.02). These results suggest family/friend events may trigger sudden cardiac arrest and raise the hypothesis that habitual vigorous physical activity may lower susceptibility to these potential triggers.

Investigating the Influence of Climate Changes on Rodent Communities at a Regional-Scale (MIS 1-3, Southwestern France)

PubMed Central

Royer, Aurélien; Montuire, Sophie; Legendre, Serge; Discamps, Emmanuel; Jeannet, Marcel; Lécuyer, Christophe

2016-01-01

Terrestrial ecosystems have continuously evolved throughout the Late Pleistocene and the Holocene, deeply affected by both progressive environmental and climatic modifications, as well as by abrupt and large climatic changes such as the Heinrich or Dansgaard-Oeschger events. Yet, the impacts of these different events on terrestrial mammalian communities are poorly known, as is the role played by potential refugia on geographical species distributions. This study examines community changes in rodents of southwestern France between 50 and 10 ky BP by integrating 94 dated faunal assemblages coming from 37 archaeological sites. This work reveals that faunal distributions were modified in response to abrupt and brief climatic events, such as Heinrich events, without actually modifying the rodent community on a regional scale. However, the succession of events which operated between the Late Pleistocene and the Holocene gradually led to establishing a new rodent community at the regional scale, with intermediate communities occurring between the Bølling and the Allerød. PMID:26789523

SEC proton prediction model: verification and analysis.

PubMed

Balch, C C

1999-06-01

This paper describes a model that has been used at the NOAA Space Environment Center since the early 1970s as a guide for the prediction of solar energetic particle events. The algorithms for proton event probability, peak flux, and rise time are described. The predictions are compared with observations. The current model shows some ability to distinguish between proton event associated flares and flares that are not associated with proton events. The comparisons of predicted and observed peak flux show considerable scatter, with an rms error of almost an order of magnitude. Rise time comparisons also show scatter, with an rms error of approximately 28 h. The model algorithms are analyzed using historical data and improvements are suggested. Implementation of the algorithm modifications reduces the rms error in the log10 of the flux prediction by 21%, and the rise time rms error by 31%. Improvements are also realized in the probability prediction by deriving the conditional climatology for proton event occurrence given flare characteristics.

AER image filtering

NASA Astrophysics Data System (ADS)

Gómez-Rodríguez, F.; Linares-Barranco, A.; Paz, R.; Miró-Amarante, L.; Jiménez, G.; Civit, A.

2007-05-01

Address Event Representation (AER) is an emergent neuromorphic interchip communication protocol that allows real-time virtual massive connectivity among huge number of neurons located on different chips.[1] By exploiting high speed digital communication circuits (with nano-seconds timing), synaptic neural connections can be time multiplexed, while neural activity signals (with mili-seconds timings) are sampled at low frequencies. Neurons generate "events" according to their activity levels. That is, more active neurons generate more events per unit time and access the interchip communication channel more frequently than neurons with low activity. In Neuromorphic system development, AER brings some advantages to develop real-time image processing system: (1) AER represents the information like time continuous stream not like a frame; (2) AER sends the most important information first (although this depends on the sender); (3) AER allows to process information as soon as it is received. When AER is used in artificial vision field, each pixel is considered like a neuron, so pixel's intensity is represented like a sequence of events; modifying the number and the frequency of these events, it is possible to make some image filtering. In this paper we present four image filters using AER: (a) Noise addition and suppression, (b) brightness modification, (c) single moving object tracking and (d) geometrical transformations (rotation, translation, reduction and magnification). For testing and debugging, we use USB-AER board developed by Robotic and Technology of Computers Applied to Rehabilitation (RTCAR) research group. This board is based on an FPGA, devoted to manage the AER functionality. This board also includes a micro-controlled for USB communication, 2 Mbytes RAM and 2 AER ports (one for input and one for output).

Coding paediatric outpatient data to provide health planners with information on children with chronic conditions and disabilities.

PubMed

Craig, Elizabeth; Kerr, Neal; McDonald, Gabrielle

2017-03-01

In New Zealand, there is a paucity of information on children with chronic conditions and disabilities (CCD). One reason is that many are managed in hospital outpatients where diagnostic coding of health-care events does not occur. This study explores the feasibility of coding paediatric outpatient data to provide health planners with information on children with CCD. Thirty-seven clinicians from six District Health Boards (DHBs) trialled coding over 12 weeks. In five DHBs, the International Classification of Diseases and Related Health Problems, 10th Edition, Australian Modification (ICD-10-AM) and Systematised Nomenclature of Medicine Clinical Terms (SNOMED-CT) were trialled for 6 weeks each. In one DHB, ICD-10-AM was trialled for 12 weeks. A random sample (30%) of ICD-10-AM coded events were also coded by clinical coders. A mix of paper and electronic methods were used. In total 2,604 outpatient events were coded in ICD-10-AM and 693 in SNOMED-CT. Dual coding occurred for 770 (29.6%) ICD-10-AM events. Overall, 34% of ICD-10-AM and 40% of SNOMED-CT events were for developmental and behavioural disorders. Chronic medical conditions were also common. Clinicians were concerned about the workload impacts, particularly for paper-based methods. Coder's were concerned about clinician's adherence to coding guidelines and the poor quality of documentation in some notes. Coded outpatient data could provide planners with a rich source of information on children with CCD. However, coding is also resource intensive. Thus its costs need to be weighed against the costs of managing a much larger health budget using very limited information. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Very low frequency radio signatures of transient luminous events above thunderstorms

NASA Astrophysics Data System (ADS)

Marshall, Robert Andrew

Lightning discharges emit intense optical and acoustic energy, in the form of lightning and thunder, respectively, but a large amount of energy is emitted as radio-frequency electromagnetic pulses (EMP). These pulses can be detected thousands of kilometers away, thanks to efficient propagation in the waveguide formed by the conducting Earth and the overlying ionosphere. In addition, intense discharges interact with the overlying ionosphere at 80-100 km altitude. The EMP-ionosphere interaction is directly observed in one manifestation as the bright transient optical emissions known as "elves", but in addition, the interaction can directly modify the free electron density in the nighttime lower ionosphere. Modifications of the ionospheric electron density can be detected via subionospheric Very Low Frequency (VLF) remote sensing. In this method, coherent signals from powerful VLF transmitters, built for submarine communication and operated by the Navy, are monitored and their amplitude and phase are tracked in time. The variations of these signais are used to sense ionospheric modifications through rapid changes in the received amplitude and/or phase when the transmitted signal propagates through an ionospheric perturbation. When these perturbations are caused by lightning, they are known as "Early VLF" perturbations, due to the negligible delay between the lightning discharge and the appearance of the VLF signal change, whereas lightning-induced electron precipitation (LEP) events have a delay of 1--2 seconds. In this work, correlations between VLF signatures and optical events are used to show that these Early VLF events may be the signature of ionospheric modification by in-cloud (IC) lightning discharges. While the more impressive cloud-to-ground (CG) lightning discharges are more commonly observed and better understood, they are outnumbered in occurrence 3:1 by IC discharges, whose effects may be relatively stronger in the overlying ionosphere. We use a 3D time-domain model of the lightning EMP-ionosphere interaction to calculate expected ionospheric density changes from IC discharges. We find that bursts of IC-EMPs can significantly modify the lower ionosphere, with both increases and decreases in electron density. We then use a frequency-domain model of the VLF transmitter signal propagation in the Earth-ionosphere waveguide to a receiver to show that these density changes are consistent with measurements. Our results demonstrate that these Early VLF events, which are ubiquitous in VLF data, are signatures of the effects of in-cloud lightning, and that they can be used to quantify the effects of IC lightning on the ionosphere during an intense thunderstorm.

Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA.

PubMed

Iyer, Lakshminarayan M; Zhang, Dapeng; Burroughs, A Maxwell; Aravind, L

2013-09-01

Discovery of the TET/JBP family of dioxygenases that modify bases in DNA has sparked considerable interest in novel DNA base modifications and their biological roles. Using sensitive sequence and structure analyses combined with contextual information from comparative genomics, we computationally characterize over 12 novel biochemical systems for DNA modifications. We predict previously unidentified enzymes, such as the kinetoplastid J-base generating glycosyltransferase (and its homolog GREB1), the catalytic specificity of bacteriophage TET/JBP proteins and their role in complex DNA base modifications. We also predict the enzymes involved in synthesis of hypermodified bases such as alpha-glutamylthymine and alpha-putrescinylthymine that have remained enigmatic for several decades. Moreover, the current analysis suggests that bacteriophages and certain nucleo-cytoplasmic large DNA viruses contain an unexpectedly diverse range of DNA modification systems, in addition to those using previously characterized enzymes such as Dam, Dcm, TET/JBP, pyrimidine hydroxymethylases, Mom and glycosyltransferases. These include enzymes generating modified bases such as deazaguanines related to queuine and archaeosine, pyrimidines comparable with lysidine, those derived using modified S-adenosyl methionine derivatives and those using TET/JBP-generated hydroxymethyl pyrimidines as biosynthetic starting points. We present evidence that some of these modification systems are also widely dispersed across prokaryotes and certain eukaryotes such as basidiomycetes, chlorophyte and stramenopile alga, where they could serve as novel epigenetic marks for regulation or discrimination of self from non-self DNA. Our study extends the role of the PUA-like fold domains in recognition of modified nucleic acids and predicts versions of the ASCH and EVE domains to be novel 'readers' of modified bases in DNA. These results open opportunities for the investigation of the biology of these systems and their use in biotechnology.

Computational identification of novel biochemical systems involved in oxidation, glycosylation and other complex modifications of bases in DNA

PubMed Central

Iyer, Lakshminarayan M.; Zhang, Dapeng; Maxwell Burroughs, A.; Aravind, L.

2013-01-01

Discovery of the TET/JBP family of dioxygenases that modify bases in DNA has sparked considerable interest in novel DNA base modifications and their biological roles. Using sensitive sequence and structure analyses combined with contextual information from comparative genomics, we computationally characterize over 12 novel biochemical systems for DNA modifications. We predict previously unidentified enzymes, such as the kinetoplastid J-base generating glycosyltransferase (and its homolog GREB1), the catalytic specificity of bacteriophage TET/JBP proteins and their role in complex DNA base modifications. We also predict the enzymes involved in synthesis of hypermodified bases such as alpha-glutamylthymine and alpha-putrescinylthymine that have remained enigmatic for several decades. Moreover, the current analysis suggests that bacteriophages and certain nucleo-cytoplasmic large DNA viruses contain an unexpectedly diverse range of DNA modification systems, in addition to those using previously characterized enzymes such as Dam, Dcm, TET/JBP, pyrimidine hydroxymethylases, Mom and glycosyltransferases. These include enzymes generating modified bases such as deazaguanines related to queuine and archaeosine, pyrimidines comparable with lysidine, those derived using modified S-adenosyl methionine derivatives and those using TET/JBP-generated hydroxymethyl pyrimidines as biosynthetic starting points. We present evidence that some of these modification systems are also widely dispersed across prokaryotes and certain eukaryotes such as basidiomycetes, chlorophyte and stramenopile alga, where they could serve as novel epigenetic marks for regulation or discrimination of self from non-self DNA. Our study extends the role of the PUA-like fold domains in recognition of modified nucleic acids and predicts versions of the ASCH and EVE domains to be novel ‘readers’ of modified bases in DNA. These results open opportunities for the investigation of the biology of these systems and their use in biotechnology. PMID:23814188

Influence of climate variability and urban areas on the flood events in Bari (Apulia, southern Italy)

NASA Astrophysics Data System (ADS)

Lonigro, Teresa; Polemio, Maurizio

2014-05-01

The Damaging Hydrogeological Events (DHEs) can be defined as the occurrence of one or more simultaneous phenomena, such as droughts, windstorms, heat waves, landslides, floods and secondary floods (i.e. rapid accumulation or pounding of surface water with very low flow velocity), causing damages. They represent a serious problem, especially in DHE-prone areas with growing urbanization, where the infiltration capability is limited by buildings and where the vulnerability is higher than other areas. The paper proposes a methodology, based on both historical and time series approaches, used for describing the influence of climatic variability and urban development on the number of phenomena observed. The historical approach is finalised to collect phenomenon historical data, very important for the comprehension of the evolution of a study area. Phenomenon historical data is useful for expanding the historical period of investigation in order to assess the occurrence trend of DHEs. The historical analysis of DHEs can support decision making and land-use planning, ultimately reducing natural risks. The time series approach includes the collection and the statistical analysis of climatic data (monthly rainfall, wet days, rainfall intensity, and temperature), useful to characterise the climate variations and trends and to roughly assess the effects of these trends on river discharge and on the triggering of landslides. The time series approach is completed by tools to analyse simultaneously all data types. The study of land use variations, with a special emphasis on the urban areas, is important to understand how the modifications occurred in the territory, especially in terms of vulnerability, could influence the occurrence of DHEs. The methodology can be applied simultaneously to floods and landslides and was tested considering the municipality of Bari (southern Italy), particularly affected by flood events. Since the climate trend (decreasing trend of rainfall and rainfall intensity and an increasing trend of wet days and temperatures) does not show favourable conditions for the increase of the annual number of damaging floods, its trend is increasing. The role of anthropogenic modifications and the mismanagement of risk-prone areas should be considered to justify the increasing occurrences of floods. A validation of this hypothesis comes from the study of land use modifications, carried out comparing different temporal levels of land use (from 1959 to 2006). The analysis shows, starting from 1959 to 2006, a significant increase in urban areas (of about 50%) on the entire regional territory. The municipality of Bari, the regional main town, has undergone a remarkable development of its urban areas, from 12.45 Km2 in 1959 to 58.82 Km2 in 2006. The consequent increased vulnerability of this area has been highlighted during the recent flood event occurred in 2005, which caused six casualties, numerous injuries and damages to roads, buildings, industries, agriculture, livestock and services. More details on previous results of this research activity were recently published (Polemio, 2010; Polemio and Lonigro, 2012). References Polemio M. (2010): Historical floods and a recent extreme rainfall event in the Murgia karstic environment (Southern Italy). Zeitschrift für Geomorphologie, 54(2): 195-219. Polemio M., Lonigro T. (2012): Variabilità climatica e ricorrenza delle calamità idrogeologiche in Puglia. Geologia dell'Ambiente, 2/2012: 262-266.

Therapeutics incorporating blood constituents.

PubMed

Charoenphol, Phapanin; Oswalt, Katie; Bishop, Corey J

2018-04-05

Blood deficiency and dysfunctionality can result in adverse events, which can primarily be treated by transfusion of blood or the re-introduction of properly functioning sub-components. Blood constituents can be engineered on the sub-cellular (i.e., DNA recombinant technology) and cellular level (i.e., cellular hitchhiking for drug delivery) for supplementing and enhancing therapeutic efficacy, in addition to rectifying dysfunctioning mechanisms (i.e., clotting). Herein, we report the progress of blood-based therapeutics, with an emphasis on recent applications of blood transfusion, blood cell-based therapies and biomimetic carriers. Clinically translated technologies and commercial products of blood-based therapeutics are subsequently highlighted and perspectives on challenges and future prospects are discussed. Blood-based therapeutics is a burgeoning field and has advanced considerably in recent years. Blood and its constituents, with and without modification (i.e., combinatorial), have been utilized in a broad spectrum of pre-clinical and clinically-translated treatments. This review article summarizes the most up-to-date progress of blood-based therapeutics in the following contexts: synthetic blood substitutes, acellular/non-recombinant therapies, cell-based therapies, and therapeutic sub-components. The article subsequently discusses clinically-translated technologies and future prospects thereof. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Large scale q-PCR reveals maize transcription factors that are regulated under water deficit in a tissue-specific manner

USDA-ARS?s Scientific Manuscript database

Water deficit stress is a major component of agricultural drought events and contributes greatly to yield loss in all crops. Genetic modification to improve water deficit tolerance is an obvious strategy to mitigate this problem and an understanding of the mechanism of adaptation to water deficit is...

78 FR 48736 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-09

...-cancelled orders. Phlx believes that this change will assist market participants in managing their orders...-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Modify the Rule Governing Modification of Orders on NASDAQ OMX PSX in the Event of an Issuer...

Version pressure feedback mechanisms for speculative versioning caches

DOEpatents

Eichenberger, Alexandre E.; Gara, Alan; O& #x27; Brien, Kathryn M.; Ohmacht, Martin; Zhuang, Xiaotong

2013-03-12

Mechanisms are provided for controlling version pressure on a speculative versioning cache. Raw version pressure data is collected based on one or more threads accessing cache lines of the speculative versioning cache. One or more statistical measures of version pressure are generated based on the collected raw version pressure data. A determination is made as to whether one or more modifications to an operation of a data processing system are to be performed based on the one or more statistical measures of version pressure, the one or more modifications affecting version pressure exerted on the speculative versioning cache. An operation of the data processing system is modified based on the one or more determined modifications, in response to a determination that one or more modifications to the operation of the data processing system are to be performed, to affect the version pressure exerted on the speculative versioning cache.

On the value of nonremovable reminders for behavior modification: an application to nail-biting (onychophagia).

PubMed

Koritzky, Gilly; Yechiam, Eldad

2011-11-01

The authors examined the effectiveness of a novel behavior modification method for dysfunctional and impulsive habits, based on nonremovable reminders (NrRs). NrRs were implemented by having participants wear nonremovable wristbands designated to constantly remind them of their resolution to quit the targeted habit (nail-biting). Participants were 80 nail-biters who resolved to quit. The NrR approach was contrasted with an aversion-based behavioral modification technique. Recovery was assessed after 3 and 6 weeks of treatment and in a 5-month follow-up. The NrR method was associated with lower drop-out rate and was as successful as the aversion-based method altogether. When considering only non-dropouts, the aversion-based method was more effective. This suggests that the use of constantly present reminders broadens the target population that can benefit from reminders in the course of behavior modification.

Protectiveness of water quality criteria for copper in western United States waters relative to predicted olfactory responses in juvenile Pacific salmon.

PubMed

DeForest, David K; Gensemer, Robert W; Van Genderen, Eric J; Gorsuch, Joseph W

2011-07-01

Copper (Cu) can impair olfaction in juvenile Pacific salmon (as well as other fishes), thus potentially inhibiting the ability of juveniles to avoid predators or to find food. Because Cu is commonly elevated in stormwater runoff in urban environments, storm events may result in elevated Cu concentrations in salmon-bearing streams. Accordingly, there is concern that existing Cu criteria, which were not derived using data for olfactory-related endpoints, may not be adequately protective of juvenile salmon. However, a modification of the US Environmental Protection Agency (USEPA) biotic ligand model (BLM) for deriving site-specific Cu criteria was recently proposed, which accounted for the sensitivity of olfactory endpoints. The modification was based on olfactory inhibition in juvenile coho salmon (Oncorhynchus kisutch) exposed to Cu in various combinations of pH, hardness, alkalinity, and dissolved organic carbon (DOC) concentrations. We used that olfactory-based BLM to derive 20% inhibition concentrations (IC20) values for Cu for 133 stream locations in the western United States. The olfactory BLM-based IC20 values were compared to the existing hardness-based Cu criteria and the USEPA's BLM-based Cu criteria for these representative natural waters of the western United States. Of the 133 sampling locations, mean hardness-dependent acute and chronic Cu criteria were below the mean olfactory-based BLM IC20 value in 122 (92%) and 129 (97%) of the waters, respectively (i.e., <20% olfactory impairment would have been predicted at the mean hardness-based Cu criteria concentrations). Waters characterized by a combination of high hardness and very low DOC were most likely to have hardness-based Cu criteria that were higher than the olfactory-based BLM IC20 values, because DOC strongly influences Cu bioavailability in the BLM. In all waters, the USEPA's current BLM-based criteria were below the mean olfactory-based BLM IC20 values, indicating that the USEPA's BLM-based criteria are protective of olfactory impairment in juvenile salmon. Copyright © 2011 SETAC.

Clients' experiences of a community based lifestyle modification program: a qualitative study.

PubMed

Chan, Ruth S M; Lok, Kris Y W; Sea, Mandy M M; Woo, Jean

2009-10-01

There is little information about how clients attending lifestyle modification programs view the outcomes. This qualitative study examined the clients' experience of a community based lifestyle modification program in Hong Kong. Semi-structured interviews were conducted with 25 clients attending the program. Clients perceived the program had positive impacts on their health and nutrition knowledge. They experienced frustration, negative emotion, lack of motivation, and pressure from others during the program. Working environment and lack of healthy food choices in restaurants were the major perceived environmental barriers for lifestyle modification. Clients valued nutritionists' capability of providing professional information and psychological support in the program. Our results suggest that nutritionist's capability of providing quality consultations and patient-centered care are important for empowering clients achieve lifestyle modification.

Simultaneous Sterilization With Surface Modification Of Plastic Bottle By Plasma-Based Ion Implantation

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

Sakudo, N.; Ikenaga, N.; Ikeda, F.

2011-01-07

Dry sterilization of polymeric material is developed. The technique utilizes the plasma-based ion implantation which is same as for surface modification of polymers. Experimental data for sterilization are obtained by using spores of Bacillus subtilis as samples. On the other hand we previously showed that the surface modification enhanced the gas barrier characteristics of plastic bottles. Comparing the implantation conditions for the sterilization experiment with those for the surface modification, we find that both sterilization and surface modification are simultaneously performed in a certain range of implantation conditions. This implies that the present bottling system for plastic vessels will bemore » simplified and streamlined by excluding the toxic peroxide water that has been used in the traditional sterilization processes.« less

Computational Efficiency of the Simplex Embedding Method in Convex Nondifferentiable Optimization

NASA Astrophysics Data System (ADS)

Kolosnitsyn, A. V.

2018-02-01

The simplex embedding method for solving convex nondifferentiable optimization problems is considered. A description of modifications of this method based on a shift of the cutting plane intended for cutting off the maximum number of simplex vertices is given. These modification speed up the problem solution. A numerical comparison of the efficiency of the proposed modifications based on the numerical solution of benchmark convex nondifferentiable optimization problems is presented.

An automatic microseismic or acoustic emission arrival identification scheme with deep recurrent neural networks

NASA Astrophysics Data System (ADS)

Zheng, Jing; Lu, Jiren; Peng, Suping; Jiang, Tianqi

2018-02-01

The conventional arrival pick-up algorithms cannot avoid the manual modification of the parameters for the simultaneous identification of multiple events under different signal-to-noise ratios (SNRs). Therefore, in order to automatically obtain the arrivals of multiple events with high precision under different SNRs, in this study an algorithm was proposed which had the ability to pick up the arrival of microseismic or acoustic emission events based on deep recurrent neural networks. The arrival identification was performed using two important steps, which included a training phase and a testing phase. The training process was mathematically modelled by deep recurrent neural networks using Long Short-Term Memory architecture. During the testing phase, the learned weights were utilized to identify the arrivals through the microseismic/acoustic emission data sets. The data sets were obtained by rock physics experiments of the acoustic emission. In order to obtain the data sets under different SNRs, this study added random noise to the raw experiments' data sets. The results showed that the outcome of the proposed method was able to attain an above 80 per cent hit-rate at SNR 0 dB, and an approximately 70 per cent hit-rate at SNR -5 dB, with an absolute error in 10 sampling points. These results indicated that the proposed method had high selection precision and robustness.

Nighttime observations of thunderstorm electrical activity from a high altitude airplane

NASA Technical Reports Server (NTRS)

Brook, M.; Rhodes, C.; Vaughan, O. H., Jr.; Orville, R. E.; Vonnegut, B.

1984-01-01

Photographs from a NASA U-2 airplane flying over nocturnal thunderstorms show frequent lightning activity in the upper part of the cloud. In some cases, unobscured segments of lightning channels 1 km or longer are visible in clear air around and above the cloud. Multiple images of lightning channels indicate multiple discharges in the same channel. Photographs taken through a diffraction grating show that the lightning has a spectrum similar to that observed in the lower troposphere. Lightning spectra obtained with a slitless line-scan spectrometer show strong singly ionized nitrogen emissions at 463.0 and 500.5 nm. Field changes measured with an electric field-change meter correlate with pulses measured with a photocell optical system. Optical signals corresponding to dart leader, return stroke, and continuing current events are readily distinguished in the scattered light emerging from the cloud surface. The variation of light intensity with time in lightning events is consistent with predicted modification of optical lightning signals by clouds. It appears that satellite based optical sensor measurements cannot provide reliable information on current rise times in return strokes. On the other hand, discrimination between cloud-to-ground and intracloud flashes and the counting of ground strokes is possible using the optical pulse pairs which have been identified with leader, return-stroke events in the cloud-to-ground flashes studied.

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth

PubMed Central

Carabetta, Valerie J.; Greco, Todd M.; Tanner, Andrew W.

2016-01-01

ABSTRACT Nε-Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. IMPORTANCE The past decade highlighted Nε-lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis. To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth. PMID:27376153

Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth.

PubMed

Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W; Cristea, Ileana M; Dubnau, David

2016-05-01

N ε -Lysine acetylation has been recognized as a ubiquitous regulatory posttranslational modification that influences a variety of important biological processes in eukaryotic cells. Recently, it has been realized that acetylation is also prevalent in bacteria. Bacteria contain hundreds of acetylated proteins, with functions affecting diverse cellular pathways. Still, little is known about the regulation or biological relevance of nearly all of these modifications. Here we characterize the cellular growth-associated regulation of the Bacillus subtilis acetylome. Using acetylation enrichment and quantitative mass spectrometry, we investigate the logarithmic and stationary growth phases, identifying over 2,300 unique acetylation sites on proteins that function in essential cellular pathways. We determine an acetylation motif, EK(ac)(D/Y/E), which resembles the eukaryotic mitochondrial acetylation signature, and a distinct stationary-phase-enriched motif. By comparing the changes in acetylation with protein abundances, we discover a subset of critical acetylation events that are temporally regulated during cell growth. We functionally characterize the stationary-phase-enriched acetylation on the essential shape-determining protein MreB. Using bioinformatics, mutational analysis, and fluorescence microscopy, we define a potential role for the temporal acetylation of MreB in restricting cell wall growth and cell diameter. The past decade highlighted N ε -lysine acetylation as a prevalent posttranslational modification in bacteria. However, knowledge regarding the physiological importance and temporal regulation of acetylation has remained limited. To uncover potential regulatory roles for acetylation, we analyzed how acetylation patterns and abundances change between growth phases in B. subtilis . To demonstrate that the identification of cell growth-dependent modifications can point to critical regulatory acetylation events, we further characterized MreB, the cell shape-determining protein. Our findings led us to propose a role for MreB acetylation in controlling cell width by restricting cell wall growth.

Long-lasting D-region ionospheric modifications, caused by intense lightning in association with elve and sprite pairs

NASA Astrophysics Data System (ADS)

Haldoupis, Christos; Cohen, Morris; Cotts, Benjamin; Arnone, Enrico; Inan, Umran

2012-08-01

Observations show that intense +CG lightning discharges which trigger both an elve and a sprite are associated with long-lasting conductivity modifications in the upper D-region ionosphere. They are observed as strong perturbations in VLF signals propagating through the disturbed region, manifested as LOng Recovery Early VLF events (LORE), which can last up to 30 minutes. These same ionospheric modifications are also responsible for step-like changes, seen mostly in off-storm VLF transmissions, which offset signal levels even for longer times. The evidence suggests that when a very intense positive cloud to ground lightning stroke leads to an elve and a high altitude sprite, and possibly a sprite halo as well, there is production of long lasting elevations in electron density at VLF reflection heights that cause LOREs and severe effects on VLF propagation. The present results confirm past predictions and postulations that elves may be accompanied by long-lasting electron density perturbations in the lower ionosphere.

Protein and DNA Modifications: Evolutionary Imprints of Bacterial Biochemical Diversification and Geochemistry on the Provenance of Eukaryotic Epigenetics

PubMed Central

Aravind, L.; Burroughs, A. Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M.

2014-01-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth’s history. PMID:24984775

Protein and DNA modifications: evolutionary imprints of bacterial biochemical diversification and geochemistry on the provenance of eukaryotic epigenetics.

PubMed

Aravind, L; Burroughs, A Maxwell; Zhang, Dapeng; Iyer, Lakshminarayan M

2014-07-01

Epigenetic information, which plays a major role in eukaryotic biology, is transmitted by covalent modifications of nuclear proteins (e.g., histones) and DNA, along with poorly understood processes involving cytoplasmic/secreted proteins and RNAs. The origin of eukaryotes was accompanied by emergence of a highly developed biochemical apparatus for encoding, resetting, and reading covalent epigenetic marks in proteins such as histones and tubulins. The provenance of this apparatus remained unclear until recently. Developments in comparative genomics show that key components of eukaryotic epigenetics emerged as part of the extensive biochemical innovation of secondary metabolism and intergenomic/interorganismal conflict systems in prokaryotes, particularly bacteria. These supplied not only enzymatic components for encoding and removing epigenetic modifications, but also readers of some of these marks. Diversification of these prokaryotic systems and subsequently eukaryotic epigenetics appear to have been considerably influenced by the great oxygenation event in the Earth's history. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Φ meson production in the forward/backward rapidity region in Cu + Au collisions at s NN = 200 GeV

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

Adare, A.; Aidala, C.; Ajitanand, N. N.

2016-02-04

The PHENIX experiment at the Relativistic Heavy Ion Collider has measured φ meson production and its nuclear modification in asymmetric Cu + Au heavy-ion collisions at √ sNN = 200 GeV at both forward Cu-going direction (1.2 < y < 2.2) and backward Au-going direction (-2.2 < y < -1.2) rapidities. The measurements are performed via the dimuon decay channel and reported as a function of the number of participating nucleons, rapidity, and transverse momentum. In the most central events, 0%–20% centrality, the φ meson yield integrated over 1 < p T < 5 GeV/c prefers a smaller value, whichmore » means a larger nuclear modification, in the Cu-going direction compared to the Au-going direction. Finally and additionally, the nuclear-modification factor in Cu + Au collisions averaged over all centrality is measured to be similar to the previous PHENIX result in d + Au collisions for these rapidities.« less

Substoichiometric hydroxynonenylation of a single protein recapitulates whole-cell-stimulated antioxidant response.

PubMed

Parvez, Saba; Fu, Yuan; Li, Jiayang; Long, Marcus J C; Lin, Hong-Yu; Lee, Dustin K; Hu, Gene S; Aye, Yimon

2015-01-14

Lipid-derived electrophiles (LDEs) that can directly modify proteins have emerged as important small-molecule cues in cellular decision-making. However, because these diffusible LDEs can modify many targets [e.g., >700 cysteines are modified by the well-known LDE 4-hydroxynonenal (HNE)], establishing the functional consequences of LDE modification on individual targets remains devilishly difficult. Whether LDE modifications on a single protein are biologically sufficient to activate discrete redox signaling response downstream also remains untested. Herein, using T-REX (targetable reactive electrophiles and oxidants), an approach aimed at selectively flipping a single redox switch in cells at a precise time, we show that a modest level (∼34%) of HNEylation on a single target is sufficient to elicit the pharmaceutically important antioxidant response element (ARE) activation, and the resultant strength of ARE induction recapitulates that observed from whole-cell electrophilic perturbation. These data provide the first evidence that single-target LDE modifications are important individual events in mammalian physiology.

ϕ meson production in the forward/backward rapidity region in Cu + Au collisions at √{sNN}=200 GeV

NASA Astrophysics Data System (ADS)

Adare, A.; Aidala, C.; Ajitanand, N. N.; Akiba, Y.; Akimoto, R.; Alexander, J.; Alfred, M.; Al-Ta'Ani, H.; Andrews, K. R.; Angerami, A.; Aoki, K.; Apadula, N.; Appelt, E.; Aramaki, Y.; Armendariz, R.; Asano, H.; Aschenauer, E. C.; Atomssa, E. T.; Awes, T. C.; Azmoun, B.; Babintsev, V.; Bai, M.; Bai, X.; Bandara, N. S.; Bannier, B.; Barish, K. N.; Bassalleck, B.; Basye, A. T.; Bathe, S.; Baublis, V.; Baumann, C.; Baumgart, S.; Bazilevsky, A.; Beaumier, M.; Beckman, S.; Belmont, R.; Ben-Benjamin, J.; Bennett, R.; Berdnikov, A.; Berdnikov, Y.; Black, D.; Blau, D. S.; Bok, J. S.; Boyle, K.; Brooks, M. L.; Broxmeyer, D.; Bryslawskyj, J.; Buesching, H.; Bumazhnov, V.; Bunce, G.; Butsyk, S.; Campbell, S.; Castera, P.; Chen, C.-H.; Chi, C. Y.; Chiu, M.; Choi, I. J.; Choi, J. B.; Choi, S.; Choudhury, R. K.; Christiansen, P.; Chujo, T.; Chvala, O.; Cianciolo, V.; Citron, Z.; Cole, B. A.; Conesa Del Valle, Z.; Connors, M.; Cronin, N.; Crossette, N.; Csanád, M.; Csörgő, T.; Dairaku, S.; Danley, T. W.; Datta, A.; Daugherity, M. S.; David, G.; Dayananda, M. K.; Deblasio, K.; Dehmelt, K.; Denisov, A.; Deshpande, A.; Desmond, E. J.; Dharmawardane, K. V.; Dietzsch, O.; Ding, L.; Dion, A.; Diss, P. B.; Do, J. H.; Donadelli, M.; D'Orazio, L.; Drapier, O.; Drees, A.; Drees, K. A.; Durham, J. M.; Durum, A.; Efremenko, Y. V.; Engelmore, T.; Enokizono, A.; En'yo, H.; Esumi, S.; Eyser, K. O.; Fadem, B.; Feege, N.; Fields, D. E.; Finger, M.; Finger, M.; Fleuret, F.; Fokin, S. L.; Frantz, J. E.; Franz, A.; Frawley, A. D.; Fukao, Y.; Fusayasu, T.; Gainey, K.; Gal, C.; Gallus, P.; Garg, P.; Garishvili, A.; Garishvili, I.; Ge, H.; Giordano, F.; Glenn, A.; Gong, X.; Gonin, M.; Goto, Y.; Granier de Cassagnac, R.; Grau, N.; Greene, S. V.; Grosse Perdekamp, M.; Gu, Y.; Gunji, T.; Guo, L.; Guragain, H.; Gustafsson, H.-Å.; Hachiya, T.; Haggerty, J. S.; Hahn, K. I.; Hamagaki, H.; Hamblen, J.; Hamilton, H. F.; Han, R.; Han, S. Y.; Hanks, J.; Harper, C.; Hasegawa, S.; Haseler, T. O. S.; Hashimoto, K.; Haslum, E.; Hayano, R.; He, X.; Hemmick, T. K.; Hester, T.; Hill, J. C.; Hollis, R. S.; Holzmann, W.; Homma, K.; Hong, B.; Horaguchi, T.; Hori, Y.; Hornback, D.; Hoshino, T.; Hotvedt, N.; Huang, J.; Huang, S.; Ichihara, T.; Ichimiya, R.; Iinuma, H.; Ikeda, Y.; Imai, K.; Imazu, Y.; Inaba, M.; Iordanova, A.; Isenhower, D.; Ishihara, M.; Isinhue, A.; Issah, M.; Ivanishchev, D.; Iwanaga, Y.; Jacak, B. V.; Jeon, S. J.; Jezghani, M.; Jia, J.; Jiang, X.; John, D.; Johnson, B. M.; Jones, T.; Joo, K. S.; Jouan, D.; Jumper, D. S.; Kamin, J.; Kanda, S.; Kaneti, S.; Kang, B. H.; Kang, J. H.; Kang, J. S.; Kapustinsky, J.; Karatsu, K.; Kasai, M.; Kawall, D.; Kazantsev, A. V.; Kempel, T.; Key, J. A.; Khachatryan, V.; Khandai, P. K.; Khanzadeev, A.; Kijima, K. M.; Kim, B. I.; Kim, C.; Kim, D. J.; Kim, E.-J.; Kim, G. W.; Kim, M.; Kim, Y.-J.; Kim, Y. K.; Kimelman, B.; Kinney, E.; Kiss, Á.; Kistenev, E.; Kitamura, R.; Klatsky, J.; Kleinjan, D.; Kline, P.; Koblesky, T.; Kochenda, L.; Kofarago, M.; Komkov, B.; Konno, M.; Koster, J.; Kotchetkov, D.; Kotov, D.; Král, A.; Krizek, F.; Kunde, G. J.; Kurita, K.; Kurosawa, M.; Kwon, Y.; Kyle, G. S.; Lacey, R.; Lai, Y. S.; Lajoie, J. G.; Lebedev, A.; Lee, D. M.; Lee, G. H.; Lee, J.; Lee, K. B.; Lee, K. S.; Lee, S.; Lee, S. H.; Lee, S. R.; Leitch, M. J.; Leite, M. A. L.; Leitgab, M.; Lewis, B.; Li, X.; Lim, S. H.; Linden Levy, L. A.; Liu, H.; Liu, M. X.; Love, B.; Lynch, D.; Maguire, C. F.; Makdisi, Y. I.; Makek, M.; Manion, A.; Manko, V. I.; Mannel, E.; Mao, Y.; Maruyama, T.; Masui, H.; McCumber, M.; McGaughey, P. L.; McGlinchey, D.; McKinney, C.; Means, N.; Meles, A.; Mendoza, M.; Meredith, B.; Miake, Y.; Mibe, T.; Mignerey, A. C.; Miki, K.; Milov, A.; Mishra, D. K.; Mitchell, J. T.; Miyachi, Y.; Miyasaka, S.; Mizuno, S.; Mohanty, A. K.; Mohapatra, S.; Montuenga, P.; Moon, H. J.; Moon, T.; Morino, Y.; Morreale, A.; Morrison, D. P.; Moskowitz, M.; Motschwiller, S.; Moukhanova, T. V.; Murakami, T.; Murata, J.; Mwai, A.; Nagae, T.; Nagamiya, S.; Nagashima, K.; Nagle, J. L.; Naglis, M.; Nagy, M. I.; Nakagawa, I.; Nakagomi, H.; Nakamiya, Y.; Nakamura, K. R.; Nakamura, T.; Nakano, K.; Nattrass, C.; Netrakanti, P. K.; Newby, J.; Nguyen, M.; Nihashi, M.; Niida, T.; Nishimura, S.; Nouicer, R.; Novák, T.; Novitzky, N.; Nyanin, A. S.; Oakley, C.; O'Brien, E.; Ogilvie, C. A.; Oide, H.; Oka, M.; Okada, K.; Orjuela Koop, J. D.; Osborn, J. D.; Oskarsson, A.; Ouchida, M.; Ozawa, K.; Pak, R.; Pantuev, V.; Papavassiliou, V.; Park, B. H.; Park, I. H.; Park, J. S.; Park, S.; Park, S. K.; Pate, S. F.; Patel, L.; Patel, M.; Pei, H.; Peng, J.-C.; Pereira, H.; Perepelitsa, D. V.; Perera, G. D. N.; Peressounko, D. Yu.; Perry, J.; Petti, R.; Pinkenburg, C.; Pinson, R.; Pisani, R. P.; Proissl, M.; Purschke, M. L.; Qu, H.; Rak, J.; Ramson, B. J.; Ravinovich, I.; Read, K. F.; Reygers, K.; Reynolds, D.; Riabov, V.; Riabov, Y.; Richardson, E.; Rinn, T.; Riveli, N.; Roach, D.; Roche, G.; Rolnick, S. D.; Rosati, M.; Rosendahl, S. S. E.; Rowan, Z.; Rubin, J. G.; Ryu, M. S.; Sahlmueller, B.; Saito, N.; Sakaguchi, T.; Sako, H.; Samsonov, V.; Sano, S.; Sarsour, M.; Sato, S.; Sato, T.; Savastio, M.; Sawada, S.; Schaefer, B.; Schmoll, B. K.; Sedgwick, K.; Seele, J.; Seidl, R.; Sekiguchi, Y.; Sen, A.; Seto, R.; Sett, P.; Sexton, A.; Sharma, D.; Shaver, A.; Shein, I.; Shibata, T.-A.; Shigaki, K.; Shim, H. H.; Shimomura, M.; Shoji, K.; Shukla, P.; Sickles, A.; Silva, C. L.; Silvermyr, D.; Silvestre, C.; Sim, K. S.; Singh, B. K.; Singh, C. P.; Singh, V.; Skolnik, M.; Slunečka, M.; Snowball, M.; Sodre, T.; Solano, S.; Soltz, R. A.; Sondheim, W. E.; Sorensen, S. P.; Sourikova, I. V.; Stankus, P. W.; Steinberg, P.; Stenlund, E.; Stepanov, M.; Ster, A.; Stoll, S. P.; Stone, M. R.; Sugitate, T.; Sukhanov, A.; Sumita, T.; Sun, J.; Sziklai, J.; Takagui, E. M.; Takahara, A.; Taketani, A.; Tanabe, R.; Tanaka, Y.; Taneja, S.; Tanida, K.; Tannenbaum, M. J.; Tarafdar, S.; Taranenko, A.; Tennant, E.; Themann, H.; Thomas, D.; Tieulent, R.; Timilsina, A.; Todoroki, T.; Togawa, M.; Tomášek, L.; Tomášek, M.; Torii, H.; Towell, C. L.; Towell, R.; Towell, R. S.; Tserruya, I.; Tsuchimoto, Y.; Utsunomiya, K.; Vale, C.; van Hecke, H. W.; Vargyas, M.; Vazquez-Zambrano, E.; Veicht, A.; Velkovska, J.; Vértesi, R.; Virius, M.; Vossen, A.; Vrba, V.; Vznuzdaev, E.; Wang, X. R.; Watanabe, D.; Watanabe, K.; Watanabe, Y.; Watanabe, Y. S.; Wei, F.; Wei, R.; Wessels, J.; Whitaker, S.; White, A. S.; White, S. N.; Winter, D.; Wolin, S.; Woody, C. L.; Wright, R. M.; Wysocki, M.; Xia, B.; Xue, L.; Yalcin, S.; Yamaguchi, Y. L.; Yang, R.; Yanovich, A.; Ying, J.; Yokkaichi, S.; Yoo, J. H.; Yoo, J. S.; Yoon, I.; You, Z.; Young, G. R.; Younus, I.; Yu, H.; Yushmanov, I. E.; Zajc, W. A.; Zelenski, A.; Zhou, S.; Zou, L.; Phenix Collaboration

2016-02-01

The PHENIX experiment at the Relativistic Heavy Ion Collider has measured ϕ meson production and its nuclear modification in asymmetric Cu +Au heavy-ion collisions at √{sNN}=200 GeV at both forward Cu-going direction (1.2

Post translational modification of Parkin.

PubMed

Chakraborty, Joy; Basso, Valentina; Ziviani, Elena

2017-02-21

Mutations in the gene encoding for the E3 ubiquitin ligase Parkin are associated to a rare form of familiar autosomal recessive Parkinsonism. Despite decades of research on the Parkin protein, whose structure has been recently solved, little is known about the specific signalling pathways that lead to Parkin activation. Parkin activity spans from mitochondria quality control to tumor suppression and stress protection; it is thus tempting to hypothesize that the broad impact of Parkin on cellular physiology might be the result of different post translational modifications that can be controlled by balanced opposing events. Sequence alignment of Parkin from different species indicates high homology between domains across Parkin orthologs and identifies highly conserved amino acid residues that, if modified, impinge on Parkin functions. In this review, we summarize findings on post translational modifications that have been shown to affect Parkin activity and stability. This article was reviewed by Prof. Dr. Konstanze F. Winklhofer and by Prof. Thomas Simmen. Both reviewers have been nominated by Professor Luca Pellegrini.

Nitric Oxide-Dependent Posttranslational Modification in Plants: An Update

PubMed Central

Astier, Jeremy; Lindermayr, Christian

2012-01-01

Nitric oxide (NO) has been demonstrated as an essential regulator of several physiological processes in plants. The understanding of the molecular mechanism underlying its critical role constitutes a major field of research. NO can exert its biological function through different ways, such as the modulation of gene expression, the mobilization of second messengers, or interplays with protein kinases. Besides this signaling events, NO can be responsible of the posttranslational modifications (PTM) of target proteins. Several modifications have been identified so far, whereas metal nitrosylation, the tyrosine nitration and the S-nitrosylation can be considered as the main ones. Recent data demonstrate that these PTM are involved in the control of a wide range of physiological processes in plants, such as the plant immune system. However, a great deal of effort is still necessary to pinpoint the role of each PTM in plant physiology. Taken together, these new advances in proteomic research provide a better comprehension of the role of NO in plant signaling. PMID:23203119

New frontiers in gene targeting and cloning: success, application and challenges in domestic animals and human embryonic stem cells.

PubMed

Denning, Chris; Priddle, Helen

2003-07-01

Until recently, precise modification of the animal genome by gene targeting was restricted to the mouse because germline competent embryonic stem cells are not available in any other mammalian species. Nuclear transfer (NT) technology now provides an alternative route for cell-based transgenesis in domestic species, offering new opportunities in genetic modification. Livestock that produce human therapeutic proteins in their milk, have organs suitable for xenotransplantation, or that could provide resistance to diseases such as spongiform encephalopathies have been produced by NT from engineered, cultured somatic cells. However, improvements in the efficiency of somatic cell gene targeting and a greater understanding of the reprogramming events that occur during NT are required for the routine application of what is currently an inefficient process. The ability to reprogramme and genetically manipulate cells will also be crucial for full exploitation of human embryonic stem (hES) cells, which offer unparalleled opportunities in human health and biotechnology. Particularly pertinent are directed differentiation of hES lines to specific cell lineages, production of cells that evade the patient's immune system and ensuring the safety of ensuing transplants. This review will discuss some of the successes, applications and challenges facing gene targeting in livestock and hES cells.

OH-PRED: prediction of protein hydroxylation sites by incorporating adapted normal distribution bi-profile Bayes feature extraction and physicochemical properties of amino acids.

PubMed

Jia, Cang-Zhi; He, Wen-Ying; Yao, Yu-Hua

2017-03-01

Hydroxylation of proline or lysine residues in proteins is a common post-translational modification event, and such modifications are found in many physiological and pathological processes. Nonetheless, the exact molecular mechanism of hydroxylation remains under investigation. Because experimental identification of hydroxylation is time-consuming and expensive, bioinformatics tools with high accuracy represent desirable alternatives for large-scale rapid identification of protein hydroxylation sites. In view of this, we developed a supporter vector machine-based tool, OH-PRED, for the prediction of protein hydroxylation sites using the adapted normal distribution bi-profile Bayes feature extraction in combination with the physicochemical property indexes of the amino acids. In a jackknife cross validation, OH-PRED yields an accuracy of 91.88% and a Matthew's correlation coefficient (MCC) of 0.838 for the prediction of hydroxyproline sites, and yields an accuracy of 97.42% and a MCC of 0.949 for the prediction of hydroxylysine sites. These results demonstrate that OH-PRED increased significantly the prediction accuracy of hydroxyproline and hydroxylysine sites by 7.37 and 14.09%, respectively, when compared with the latest predictor PredHydroxy. In independent tests, OH-PRED also outperforms previously published methods.

Chemically Derivatized Semiconductor Photoelectrodes.

ERIC Educational Resources Information Center

Wrighton, Mark S.

1983-01-01

Deliberate modification of semiconductor photoelectrodes to improve durability and enhance rate of desirable interfacial redox processes is discussed for a variety of systems. Modification with molecular-based systems or with metals/metal oxides yields results indicating an important role for surface modification in devices for fundamental study…

Effective secondary prevention through cardiac rehabilitation after coronary revascularization and predictors of poor adherence to lifestyle modification and medication. Results of the ICAROS Survey.

PubMed

Griffo, Raffaele; Ambrosetti, Marco; Tramarin, Roberto; Fattirolli, Francesco; Temporelli, Pier Luigi; Vestri, Anna Rita; De Feo, Stefania; Tavazzi, Luigi

2013-08-20

Secondary prevention is a priority after coronary revascularization. We investigate the impact of a cardiac rehabilitation (CR) program on lifestyle, risk factors and medication modifications and analyze predictors of poor behavioral changes and events in patients after coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Multicenter (n=62), prospective, longitudinal survey in post-CABG or -PCI consecutive patients after a comprehensive CR program. Cardiac risk factors, lifestyle habits, medication and 1 year cardiovascular events were collected. Logistic regression analyzed the association between risk factors, events and predictors of non-adherence to treatment and lifestyle. At 1 year, of the 1262 patients (66 ± 10 years, CABG 69%, PCI 31%), 94% were taking antiplatelet agents (vs. 91.8% at CR admission and 91.7% at CR discharge, p=ns), 87% statins (vs. 67.5%, p<.0001, and 86.3%, p=ns), 80.7% beta-blockers (vs. 67.4%, p<.0001, and 88.8%, p=ns), and 81.1% ACE inhibitors (vs. 57.5% p<.0001, and 77.7%, p=ns). 89.9% of the patients showed good adherence to treatment, 72% adhered to diet and 51% to exercise recommendations; 74% of smokers stopped smoking. Younger age was predictive of smoking resumption (OR 8.9, CI 3.5-22.8). Pre-event sedentary lifestyle (OR 3.3, CI 1.3-8.7) was predictive of poor diet. Older patients with comorbidity (OR 3.1; CI, 1.8-5.2) tended to persist in sedentary lifestyle and discontinue therapy and diet recommendations. Age, diabetes, smoking and PCI indication were predictors of recurrent CV events which occurred in 142 patients. Participation in CR results in excellent treatment after revascularization, as well as a good lifestyle and medication adherence at 1 year and provides further confirmation of the benefit of secondary prevention. Several clinical characteristics may predict poor behavioral changes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Aspirin for the Primary Prevention of Cardiovascular Events: A Systematic Evidence Review for the U.S. Preventive Services Task Force.

PubMed

Guirguis-Blake, Janelle M; Evans, Corinne V; Senger, Caitlyn A; O'Connor, Elizabeth A; Whitlock, Evelyn P

2016-06-21

Cardiovascular disease (CVD) is the leading cause of death in the United States. To update a systematic review about the benefits of aspirin for the primary prevention of cardiovascular events in adults aged 40 years or older and to evaluate effect modification in subpopulations. MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (January 2008 to January 2015), and Cochrane Database of Systematic Reviews. Two investigators independently reviewed 3396 abstracts and 65 articles according to prespecified criteria. All included trials evaluated aspirin for the primary prevention of cardiovascular events. Two investigators assessed study quality; data were abstracted by 1 reviewer and checked by a second. Two good-quality and 9 fair-quality randomized, controlled trials were identified. In analyses of all doses, aspirin reduced the risk for nonfatal myocardial infarction (MI) (relative risk [RR], 0.78 [95% CI, 0.71 to 0.87]) but not nonfatal stroke; aspirin showed little or no benefit for all-cause or cardiovascular mortality. Benefits began within the first 5 years. Older adults achieved greater relative MI reduction, but no other effect modifications were found in analyzed subpopulations. In trials with aspirin doses of 100 mg or less per day, the reduction in nonfatal MI benefit persisted (absolute risk reduction, 0.15 to 1.43 events per 1000 person-years) and a 14% reduction in nonfatal stroke benefit was noted, but no benefit was found for all-cause mortality (RR, 0.95 [CI, 0.89 to 1.01]) or cardiovascular mortality (RR, 0.97 [CI, 0.85 to 1.10]). Evidence for aspirin in primary prevention is heterogeneous and limited by rare events and few credible subgroup analyses. The beneficial effect of aspirin for the primary prevention of CVD is modest and occurs at doses of 100 mg or less per day. Older adults seem to achieve a greater relative MI benefit. Agency for Healthcare Research and Quality.

Coating Systems for Magnesium-Based Biomaterials — State of the Art

NASA Astrophysics Data System (ADS)

Waterman, J.; Staiger, M. P.

Magnesium and its alloys have the potential to be used for biodegradable orthopedic implants. However, the corrosion rate in physiological conditions is too high for most applications. For this reason, surface modification to slow the corrosion rate is of great interest. Such modifications must remain biologically compatible as well as protective in corrosive environments. What follows is a brief review of recent research in inorganic coatings and surface modifications to create coatings for magnesium-based biomaterials.

Implementation of Lifestyle Modification Program Focusing on Physical Activity and Dietary Habits in a Large Group, Community-Based Setting.

PubMed

Stoutenberg, Mark; Falcon, Ashley; Arheart, Kris; Stasi, Selina; Portacio, Francia; Stepanenko, Bryan; Lan, Mary L; Castruccio-Prince, Catarina; Nackenson, Joshua

2017-06-01

Lifestyle modification programs improve several health-related behaviors, including physical activity (PA) and nutrition. However, few of these programs have been expanded to impact a large number of individuals in one setting at one time. Therefore, the purpose of this study was to determine whether a PA- and nutrition-based lifestyle modification program could be effectively conducted using a large group format in a community-based setting. One hundred twenty-one participants enrolled in a 16-week, community-based lifestyle modification program and separated in small teams of 13 to 17 individuals. Height, weight, fruit and vegetable (FAV) consumption, physical fitness, and several psychosocial measures were assessed before and after the program. Significant improvements in 6-minute walk distance (+68.3 m; p < .001), chair stands (+6.7 repetitions; p < .001), FAV servings (+1.8 servings/day; p < .001), body weight (-3.2 lbs; p < .001), as well as PA social support and eating habits self-efficacy were observed. Our lifestyle modification program was also successful in shifting participants to higher levels of stages of change for nutrition and PA, increasing overall levels of self-efficacy for healthy eating, and improving levels of social support for becoming more active. A lifestyle modification program can be successfully implemented in a community setting using a large group format to improve PA and FAV attitudes and behaviors.

Comparison of recent S-wave indicating methods

NASA Astrophysics Data System (ADS)

Hubicka, Katarzyna; Sokolowski, Jakub

2018-01-01

Seismic event consists of surface waves and body waves. Due to the fact that the body waves are faster (P-waves) and more energetic (S-waves) in literature the problem of their analysis is taken more often. The most universal information that is received from the recorded wave is its moment of arrival. When this information is obtained from at least four seismometers in different locations, the epicentre of the particular event can be estimated [1]. Since the recorded body waves may overlap in signal, the problem of wave onset moment is considered more often for faster P-wave than S-wave. This however does not mean that the issue of S-wave arrival time is not taken at all. As the process of manual picking is time-consuming, methods of automatic detection are recommended (these however may be less accurate). In this paper four recently developed methods estimating S-wave arrival are compared: the method operating on empirical mode decomposition and Teager-Kaiser operator [2], the modification of STA/LTA algorithm [3], the method using a nearest neighbour-based approach [4] and the algorithm operating on characteristic of signals' second moments. The methods will be also compared to wellknown algorithm based on the autoregressive model [5]. The algorithms will be tested in terms of their S-wave arrival identification accuracy on real data originating from International Research Institutions for Seismology (IRIS) database.

Preparation of Mach-Zehnder interferometric photonic biosensors by inkjet printing technology

NASA Astrophysics Data System (ADS)

Strasser, Florian; Melnik, Eva; Muellner, Paul; Jiménez-Meneses, Pilar; Nechvile, Magdalena; Koppitsch, Guenther; Lieberzeit, Peter; Laemmerhofer, Michael; Heer, Rudolf; Hainberger, Rainer

2017-05-01

Inkjet printing is a versatile method to apply surface modification procedures in a spatially controlled, cost-effective and mass-fabrication compatible manner. Utilizing this technology, we investigate two different approaches for functionalizing label-free optical waveguide based biosensors: a) surface modification with amine-based functional polymers (biotin-modified polyethylenimine (PEI-B)) employing active ester chemistry and b) modification with dextran based hydrogel thin films employing photoactive benzophenone crosslinker moieties. Whereas the modification with PEI-B ensures high receptor density at the surface, the hydrogel films can serve both as a voluminous matrix binding matrix and as a semipermeable separation layer between the sensor surface and the sample. We use the two surface modification strategies both individually and in combination for binding studies towards the detection of the protein inflammation biomarker, C-reactive protein (CRP). For the specific detection of CRP, we compare two kinds of capture molecules, namely biotinylated antibodies and biotinylated CRP-specific DNA based aptamers. Both kinds of capture molecules were immobilized on the PEI-B by means of streptavidin-biotin affinity binding. As transducer, we use an integrated four-channel silicon nitride (Si3N4) waveguide based Mach-Zehnder interferometric (MZI) photonic sensing platform operating at a wavelength of 850nm (TM-mode).

Treating Retentive Encopresis: Dietary Modification and Behavioral Techniques.

ERIC Educational Resources Information Center

Nabors, Laura; Morgan, Sam B.

1995-01-01

A home-based contingency management program, consisting of diet modification, laxatives, correction for soiling accidents, stimulus control training, and positive reinforcement, was implemented for treatment of a 4-year-old encopretic male. The findings provide evidence supporting the effectiveness of dietary modification combined with behavior…

Influence of major-groove chemical modifications of DNA on transcription by bacterial RNA polymerases

PubMed Central

Raindlová, Veronika; Janoušková, Martina; Slavíčková, Michaela; Perlíková, Pavla; Boháčová, Soňa; Milisavljevič, Nemanja; Šanderová, Hana; Benda, Martin; Barvík, Ivan; Krásný, Libor; Hocek, Michal

2016-01-01

DNA templates containing a set of base modifications in the major groove (5-substituted pyrimidines or 7-substituted 7-deazapurines bearing H, methyl, vinyl, ethynyl or phenyl groups) were prepared by PCR using the corresponding base-modified 2′-deoxyribonucleoside triphosphates (dNTPs). The modified templates were used in an in vitro transcription assay using RNA polymerase from Bacillus subtilis and Escherichia coli. Some modified nucleobases bearing smaller modifications (H, Me in 7-deazapurines) were perfectly tolerated by both enzymes, whereas bulky modifications (Ph at any nucleobase) and, surprisingly, uracil blocked transcription. Some middle-sized modifications (vinyl or ethynyl) were partly tolerated mostly by the E. coli enzyme. In all cases where the transcription proceeded, full length RNA product with correct sequence was obtained indicating that the modifications of the template are not mutagenic and the inhibition is probably at the stage of initiation. The results are promising for the development of bioorthogonal reactions for artificial chemical switching of the transcription. PMID:27001521

Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics

NASA Astrophysics Data System (ADS)

Aguilar, Carlos A.; Craighead, Harold G.

2013-10-01

Deoxyribonucleic acid (DNA) is the blueprint on which life is based and transmitted, but the way in which chromatin -- a dynamic complex of nucleic acids and proteins -- is packaged and behaves in the cellular nucleus has only begun to be investigated. Epigenetic modifications sit 'on top of' the genome and affect how DNA is compacted into chromatin and transcribed into ribonucleic acid (RNA). The packaging and modifications around the genome have been shown to exert significant influence on cellular behaviour and, in turn, human development and disease. However, conventional techniques for studying epigenetic or conformational modifications of chromosomes have inherent limitations and, therefore, new methods based on micro- and nanoscale devices have been sought. Here, we review the development of these devices and explore their use in the study of DNA modifications, chromatin modifications and higher-order chromatin structures.

Trial-Based Functional Analysis Informs Treatment for Vocal Scripting.

PubMed

Rispoli, Mandy; Brodhead, Matthew; Wolfe, Katie; Gregori, Emily

2018-05-01

Research on trial-based functional analysis has primarily focused on socially maintained challenging behaviors. However, procedural modifications may be necessary to clarify ambiguous assessment results. The purposes of this study were to evaluate the utility of iterative modifications to trial-based functional analysis on the identification of putative reinforcement and subsequent treatment for vocal scripting. For all participants, modifications to the trial-based functional analysis identified a primary function of automatic reinforcement. The structure of the trial-based format led to identification of social attention as an abolishing operation for vocal scripting. A noncontingent attention treatment was evaluated using withdrawal designs for each participant. This noncontingent attention treatment resulted in near zero levels of vocal scripting for all participants. Implications for research and practice are presented.

Darwinian perspectives on the evolution of human languages.

PubMed

Pagel, Mark

2017-02-01

Human languages evolve by a process of descent with modification in which parent languages give rise to daughter languages over time and in a manner that mimics the evolution of biological species. Descent with modification is just one of many parallels between biological and linguistic evolution that, taken together, offer up a Darwinian perspective on how languages evolve. Combined with statistical methods borrowed from evolutionary biology, this Darwinian perspective has brought new opportunities to the study of the evolution of human languages. These include the statistical inference of phylogenetic trees of languages, the study of how linguistic traits evolve over thousands of years of language change, the reconstruction of ancestral or proto-languages, and using language change to date historical events.

Visualization of Pulsar Search Data

NASA Astrophysics Data System (ADS)

Foster, R. S.; Wolszczan, A.

1993-05-01

The search for periodic signals from rotating neutron stars or pulsars has been a computationally taxing problem to astronomers for more than twenty-five years. Over this time interval, increases in computational capability have allowed ever more sensitive searches, covering a larger parameter space. The volume of input data and the general presence of radio frequency interference typically produce numerous spurious signals. Visualization of the search output and enhanced real-time processing of significant candidate events allow the pulsar searcher to optimally processes and search for new radio pulsars. The pulsar search algorithm and visualization system presented in this paper currently runs on serial RISC based workstations, a traditional vector based super computer, and a massively parallel computer. A description of the serial software algorithm and its modifications for massively parallel computing are describe. The results of four successive searches for millisecond period radio pulsars using the Arecibo telescope at 430 MHz have resulted in the successful detection of new long-period and millisecond period radio pulsars.

Estimated GFR and incident cardiovascular disease events in American Indians: the Strong Heart Study.

PubMed

Shara, Nawar M; Wang, Hong; Mete, Mihriye; Al-Balha, Yaman Rai; Azalddin, Nameer; Lee, Elisa T; Franceschini, Nora; Jolly, Stacey E; Howard, Barbara V; Umans, Jason G

2012-11-01

In populations with high prevalences of diabetes and obesity, estimating glomerular filtration rate (GFR) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation may predict cardiovascular disease (CVD) risk better than by using the Modification of Diet in Renal Disease (MDRD) Study equation. Longitudinal cohort study comparing the association of GFR estimated using either the CKD-EPI or MDRD Study equation with incident CVD outcomes. American Indians participating in the Strong Heart Study, a longitudinal population-based cohort with high prevalences of diabetes, CVD, and CKD. Estimated GFR (eGFR) predicted using the CKD-EPI and MDRD Study equations. Fatal and nonfatal cardiovascular events, consisting of coronary heart disease, stroke, and heart failure. The association between eGFR and outcomes was explored in Cox proportional hazards models adjusted for traditional risk factors and albuminuria; the net reclassification index and integrated discrimination improvement were determined for the CKD-EPI versus MDRD Study equations. In 4,549 participants, diabetes was present in 45%; CVD, in 7%; and stages 3-5 CKD, in 10%. During a median of 15 years, there were 1,280 cases of incident CVD, 929 cases of incident coronary heart disease, 305 cases of incident stroke, and 381 cases of incident heart failure. Reduced eGFR (<90 mL/min/1.73 m2) was associated with adverse events in most models. Compared with the MDRD Study equation, the CKD-EPI equation correctly reclassified 17.0% of 2,151 participants without incident CVD to a lower risk (higher eGFR) category and 1.3% (n=28) were reclassified incorrectly to a higher risk (lower eGFR) category. Single measurements of eGFR and albuminuria at study visits. Although eGFR based on either equation had similar associations with incident CVD, coronary heart disease, stroke, and heart failure events, in those not having events, reclassification of participants to eGFR categories was superior using the CKD-EPI equation compared with the MDRD Study equation. Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Evolution Is an Experiment: Assessing Parallelism in Crop Domestication and Experimental Evolution: (Nei Lecture, SMBE 2014, Puerto Rico).

PubMed

Gaut, Brandon S

2015-07-01

In this commentary, I make inferences about the level of repeatability and constraint in the evolutionary process, based on two sets of replicated experiments. The first experiment is crop domestication, which has been replicated across many different species. I focus on results of whole-genome scans for genes selected during domestication and ask whether genes are, in fact, selected in parallel across different domestication events. If genes are selected in parallel, it implies that the number of genetic solutions to the challenge of domestication is constrained. However, I find no evidence for parallel selection events either between species (maize vs. rice) or within species (two domestication events within beans). These results suggest that there are few constraints on genetic adaptation, but conclusions must be tempered by several complicating factors, particularly the lack of explicit design standards for selection screens. The second experiment involves the evolution of Escherichia coli to thermal stress. Unlike domestication, this highly replicated experiment detected a limited set of genes that appear prone to modification during adaptation to thermal stress. However, the number of potentially beneficial mutations within these genes is large, such that adaptation is constrained at the genic level but much less so at the nucleotide level. Based on these two experiments, I make the general conclusion that evolution is remarkably flexible, despite the presence of epistatic interactions that constrain evolutionary trajectories. I also posit that evolution is so rapid that we should establish a Speciation Prize, to be awarded to the first researcher who demonstrates speciation with a sexual organism in the laboratory. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Reassessment of 50 years of seismicity in Simav-Gediz grabens (Western Turkey), based on earthquake relocations

NASA Astrophysics Data System (ADS)

Karasozen, E.; Nissen, E.; Bergman, E. A.; Walters, R. J.

2013-12-01

Western Turkey is a rapidly deforming region with a long history of high-magnitude normal faulting earthquakes. However, the locations and slip rates of the responsible faults are poorly constrained. Here, we reassess a series of large instrumental earthquakes in the Simav-Gediz region, an area exhibiting a strong E-W gradient in N-S extension rates, from low rates bordering the Anatolian Plateau to much higher rates in the west. We start with investigating a recent Mw 5.9 earthquake at Simav (19 May 2011) using InSAR, teleseismic body-wave modeling and field observations. Next, we exploit the small but clear InSAR signal to relocate a series of older, larger earthquakes, using a calibrated earthquake relocation method which is based on the hypocentroidial decomposition (HDC) method for multiple event relocation. These improved locations in turn provide an opportunity to reassess the regional style of deformation. One interesting aspect of these earthquakes is that the largest (the Mw 7.2 Gediz earthquake, March 1970) occurred in an area of slow extension and indistinct surface faulting, whilst the well-defined and more rapidly extending Simav graben has ruptured in several smaller, Mw 6 events. However, our relocations highlight the existence of a significant gap in instrumental earthquakes along the central Simav graben, which, if it ruptured in a single event, could equal ~Mw 7. We were unable to identify fault scarps along this section due to dense vegetation and human modification, and we suggest that acquiring LiDAR data in this area should be a high priority in order to properly investigate earthquake hazard in the Simav graben.

Hydraulic stimulation or low water injection in fractured reservoir of the geothermal well GRT-1 at Rittershoffen (France)?

NASA Astrophysics Data System (ADS)

Vidal, J.; Genter, A.; Schmittbuhl, J.; Baujard, C.

2016-12-01

In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement. In the Upper Rhine Graben, several deep geothermal projects, such as at Soultz-sous-Forêts (France) or Basel (Switzerland), were based on the Enhanced Geothermal System technology. The principle underlying this technology consists of increasing the low initial natural hydraulic performance of pre-existing natural fractures in the geothermal granitic reservoir via hydraulic and/or chemical stimulations. Hydraulic stimulation consists of injection of a large amount of water at a high flow rate to promote hydroshearing of pre-existing fractures. At Soultz-sous-Forêts and Basel, the maximum wellhead pressures were 16 MPa and 30 MPa respectively which induced larger magnitude seismic events of 2.9 and 3.4 respectively. Those specific induced seismicity events were felt by local population. At Rittershoffen (France), the geothermal well GRT-1 was drilled in 2012 down to a depth of 2.6 km and penetrates fractured sandstones and granite. The reservoir temperature reaches more than 160°C but the production flowrate was too low for an industrial project economically viable. Thus, the well was subjected to Thermal, Chemical and Hydraulic stimulations, which improved the injectivity index five-fold. During the hydraulic operation, a moderate volume of water was injected from the wellhead with a low pressure of 3 MPa. Approximately 300 microseismic events were detected during the hydraulic stimulations. Due to the low wellhead pressure during injection, no events were felt by nearby residents. The goal of the study was to assess the impact of the stimulation by comparing pre- and post-stimulation acoustic image logs. This comparison revealed minor modifications of almost all the natural fractures. However, not all of these fractures are associated with permeability enhancement. The most important permeability enhancement was observed on the originally permeable fault zone affecting the top of the granitic basement.

20 CFR 668.750 - Under what circumstances can we or the INA grantee modify the terms of the grantee's plan(s)?

Code of Federal Regulations, 2012 CFR

2012-04-01

... modify the INA grantee's plan to add funds or, if required by Congressional action, to reduce the amount... add, expand, delete, or diminish any service allowable under the regulations in this part. The INA... event that further clarification or modification is required, we may extend the thirty (30) day time...

20 CFR 668.750 - Under what circumstances can we or the INA grantee modify the terms of the grantee's plan(s)?

Code of Federal Regulations, 2014 CFR

2014-04-01

... modify the INA grantee's plan to add funds or, if required by Congressional action, to reduce the amount... add, expand, delete, or diminish any service allowable under the regulations in this part. The INA... event that further clarification or modification is required, we may extend the thirty (30) day time...

20 CFR 668.750 - Under what circumstances can we or the INA grantee modify the terms of the grantee's plan(s)?

Code of Federal Regulations, 2013 CFR

2013-04-01

... modify the INA grantee's plan to add funds or, if required by Congressional action, to reduce the amount... add, expand, delete, or diminish any service allowable under the regulations in this part. The INA... event that further clarification or modification is required, we may extend the thirty (30) day time...

Dental twinning anomalies: the nomenclature enigma.

PubMed

Killian, C M; Croll, T P

1990-07-01

Dental twinning results from abnormal events in the embryologic development of teeth. This paper describes the impossibility of assigning precise diagnostic terms, such as germination, fusion, macrodontia, and concrescence, to dental twinning anomalies because the entire course of odontogenesis cannot be witnessed. Traditional nomenclature is reviewed and seven cases that exemplify the principle are presented. Modification of nomenclature to describe dental twinning defects is suggested.

Providing for the Establishment of the Select Committee on the Events Surrounding the 2012 Terrorist Attack in Benghazi.

THOMAS, 113th Congress

Rep. Sessions, Pete [R-TX-32

2014-05-06

House - 05/08/2014 Mr. Sessions asked unanimous consent to modify H. Res. 567 in the form he had placed at the desk. Without objection, the modification was agreed to. (All Actions) Tracker: This bill has the status Agreed to in HouseHere are the steps for Status of Legislation:

Impact of early life stress on the pathogenesis of mental disorders: relation to brain oxidative stress.

PubMed

Schiavone, Stefania; Colaianna, Marilena; Curtis, Logos

2015-01-01

Stress is an inevitable part of human life and it is experienced even before birth. Stress to some extent could be considered normal and even necessary for the survival and the regular psychological development during childhood or adolescence. However, exposure to prolonged stress could become harmful and strongly impact mental health increasing the risk of developing psychiatric disorders. Recent studies have attempted to clarify how the human central nervous system (CNS) reacts to early life stress, focusing mainly on neurobiological modifications. Oxidative stress, defined as a disequilibrium between the oxidant generation and the antioxidant response, has been recently described as a candidate for most of the observed modifications. In this review, we will discuss how prolonged stressful events during childhood or adolescence (such as early maternal separation, parental divorce, physical violence, sexual or psychological abuses, or exposure to war events) can lead to increased oxidative stress in the CNS and enhance the risk to develop psychiatric diseases such as anxiety, depression, drug abuse or psychosis. Defining the sources of oxidative stress following exposure to early life stress might open new beneficial insights in therapeutic approaches to these mental disorders.

A saga of cancer epigenetics: linking epigenetics to alternative splicing.

PubMed

Narayanan, Sathiya Pandi; Singh, Smriti; Shukla, Sanjeev

2017-03-07

The discovery of an increasing number of alternative splicing events in the human genome highlighted that ∼94% of genes generate alternatively spliced transcripts that may produce different protein isoforms with diverse functions. It is now well known that several diseases are a direct and indirect consequence of aberrant splicing events in humans. In addition to the conventional mode of alternative splicing regulation by ' cis ' RNA-binding sites and ' trans' RNA-binding proteins, recent literature provides enormous evidence for epigenetic regulation of alternative splicing. The epigenetic modifications may regulate alternative splicing by either influencing the transcription elongation rate of RNA polymerase II or by recruiting a specific splicing regulator via different chromatin adaptors. The epigenetic alterations and aberrant alternative splicing are known to be associated with various diseases individually, but this review discusses/highlights the latest literature on the role of epigenetic alterations in the regulation of alternative splicing and thereby cancer progression. This review also points out the need for further studies to understand the interplay between epigenetic modifications and aberrant alternative splicing in cancer progression. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Observation of medium induced modifications of jet fragmentation in PbPb collisions using isolated-photon-tagged jets

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

Sirunyan, Albert M; et al.

Measurements of fragmentation functions for jets associated with an isolated photon are presented for the first time in pp and PbPb collisions. The analysis uses data collected with the CMS detector at the CERN LHC at a nucleon-nucleon center-of-mass energy of 5.02 TeV. Fragmentation functions are obtained for jets with pmore » $$_\\mathrm{T}^\\text{jet} >$$ 30 GeV in events containing an isolated photon with p$$_\\mathrm{T}^\\gamma>$$ 60 GeV, using charged tracks with transverse momentum p$$_\\mathrm{T}^\\text{trk} >$$ 1 GeV in a cone around the jet axis. The association with an isolated photon constrains the initial p$$_\\mathrm{T}$$ and azimuthal angle of the parton whose shower produced the jet. For central PbPb collisions, modifications of the jet fragmentation functions are observed when compared to those measured in pp collisions, while no significant differences are found in the 50% most peripheral collisions. Jets in central PbPb events show an excess (depletion) of low (high) p$$_\\mathrm{T}$$ particles, with a transition around 3 GeV.« less

40 CFR 147.2927 - Permit modification.

Code of Federal Regulations, 2012 CFR

2012-07-01

... standards on which the permit was based have changed. (4) The Regional Administrator has received notice of a proposed permit transfer. (5) An interested person requests in writing that a permit be modified... appropriate. (b) Minor modifications. (1) Minor modifications do not require that the procedures listed in...

Study report on modification of the long term circulatory model for the simulation of bed rest

NASA Technical Reports Server (NTRS)

Leonard, J. I.; Grounds, D. J.

1977-01-01

Modifications were made of the circulatory, fluid, and electrolyte control model which was based on the model of Guyton. The modifications included separate leg compartments and the addition of gravity dependency. It was found that these modifications allowed for more accurate bed rest simulation by simulating changes in the orthostatic gradient and simulating the response to the fluid shifts associated with bed rest.

Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress.

PubMed

Laperrousaz, B; Berguiga, L; Nicolini, F E; Martinez-Torres, C; Arneodo, A; Satta, V Maguer; Argoul, F

2016-06-02

Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events.

Track reconstruction and particle identification developments for a study of event-by-event fluctuations in heavy ion collisions at NICA

NASA Astrophysics Data System (ADS)

Mudrokh, A. A.; Zinchenko, A. I.

2017-01-01

A Monte Carlo simulation of heavy ion collisions (Au+Au) has been performed at MPD (Multi Purpose Detector) at NICA (Dubna) for a study of the possible critical point in the phase diagram of the hot nuclear matter. The simulation took into account real detector effects with as many details as possible to properly describe the apparatus response. Particle identification (PID) has been tuned to account for modifications in track reconstruction. Some results on hadron identification in the TPC and TOF (Time Of Flight) detectors with realistically simulated response have been also obtained.

Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress

NASA Astrophysics Data System (ADS)

Laperrousaz, B.; Berguiga, L.; Nicolini, F. E.; Martinez-Torres, C.; Arneodo, A.; Maguer Satta, V.; Argoul, F.

2016-06-01

Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events.

Single inclusive jet production and the nuclear modification ratio at very forward rapidity in proton-lead collisions with √{sNN } = 5.02 TeV

NASA Astrophysics Data System (ADS)

Bury, Marcin; Van Haevermaet, Hans; Van Hameren, Andreas; Van Mechelen, Pierre; Kutak, Krzysztof; Serino, Mirko

2018-05-01

We present calculations of single inclusive jet transverse momentum and energy spectra at forward rapidity (5.2 < y < 6.6) in proton-lead collisions with √{sNN } = 5.02 TeV. The predictions are obtained with the KaTie Monte Carlo event generator, which allows to calculate interactions within the High Energy Factorisation framework. The tree-level matrix element results are subsequently interfaced with the CASCADE Monte Carlo event generator to account for hadronisation. The effects of the saturation of the gluon density, leading to suppression of the cross section, are investigated.

Role of Equatorial Anomaly in Earthquake time precursive features: A few strong events over West Pacific zone

NASA Astrophysics Data System (ADS)

Devi, Minakshi; Patgiri, S.; Barbara, A. K.; Oyama, Koh-Ichiro; Ryu, K.; Depuev, V.; Depueva, A.

2018-03-01

The earthquake (EQ) time coupling processes between equator-low-mid latitude ionosphere are complex due to inherent dynamical status of each latitudinal zone and qualified geomagnetic roles working in the system. In an attempt to identify such process, the paper presents temporal and latitudinal variations of ionization density (foF2) covering 45°N to 35°S, during a number of earthquake events (M > 5.5). The approaches adopted for extraction of features by the earthquake induced preparatory processes are discussed in the paper through identification of parameters like the 'EQ time modification in density gradient' defined by δ = (foF2 max - foF2 min)/τmm, where τmm - time span (in days) between EQ modified density maximum and minimum, and the Earthquake time Equatorial Anomaly, i.e. EEA, one of the most significant phenomenon which develops even during night time irrespective of epicenter position. Based on the observations, the paper presents the seismic time coupling dynamics through anomaly like manifestations between equator, low and mid latitude ionosphere bringing in the global Total Electron Content (TEC) features as supporting indices.

Dead-time optimized time-correlated photon counting instrument with synchronized, independent timing channels

NASA Astrophysics Data System (ADS)

Wahl, Michael; Rahn, Hans-Jürgen; Gregor, Ingo; Erdmann, Rainer; Enderlein, Jörg

2007-03-01

Time-correlated single photon counting is a powerful method for sensitive time-resolved fluorescence measurements down to the single molecule level. The method is based on the precisely timed registration of single photons of a fluorescence signal. Historically, its primary goal was the determination of fluorescence lifetimes upon optical excitation by a short light pulse. This goal is still important today and therefore has a strong influence on instrument design. However, modifications and extensions of the early designs allow for the recovery of much more information from the detected photons and enable entirely new applications. Here, we present a new instrument that captures single photon events on multiple synchronized channels with picosecond resolution and over virtually unlimited time spans. This is achieved by means of crystal-locked time digitizers with high resolution and very short dead time. Subsequent event processing in programmable logic permits classical histogramming as well as time tagging of individual photons and their streaming to the host computer. Through the latter, any algorithms and methods for the analysis of fluorescence dynamics can be implemented either in real time or offline. Instrument test results from single molecule applications will be presented.

RNA-Seq analyses reveal the order of tRNA processing events and the maturation of C/D box and CRISPR RNAs in the hyperthermophile Methanopyrus kandleri

PubMed Central

Su, Andreas A. H.; Tripp, Vanessa; Randau, Lennart

2013-01-01

The methanogenic archaeon Methanopyrus kandleri grows near the upper temperature limit for life. Genome analyses revealed strategies to adapt to these harsh conditions and elucidated a unique transfer RNA (tRNA) C-to-U editing mechanism at base 8 for 30 different tRNA species. Here, RNA-Seq deep sequencing methodology was combined with computational analyses to characterize the small RNome of this hyperthermophilic organism and to obtain insights into the RNA metabolism at extreme temperatures. A large number of 132 small RNAs were identified that guide RNA modifications, which are expected to stabilize structured RNA molecules. The C/D box guide RNAs were shown to exist as circular RNA molecules. In addition, clustered regularly interspaced short palindromic repeats RNA processing and potential regulatory RNAs were identified. Finally, the identification of tRNA precursors before and after the unique C8-to-U8 editing activity enabled the determination of the order of tRNA processing events with termini truncation preceding intron removal. This order of tRNA maturation follows the compartmentalized tRNA processing order found in Eukaryotes and suggests its conservation during evolution. PMID:23620296

Narrow infrasound pulses from lightning; are they of electrostatic or thermal origin?

NASA Astrophysics Data System (ADS)

CHUM, Jaroslav; Diendorfer, Gerhard; Šindelářová, Tereza; Baše, Jiří; Hruška, František

2014-05-01

Narrow (~1-2 s) infrasound pulses that followed, with ~11 to ~50 s delays, rapid changes of electrostatic field were observed by a microbarometer array in the Czech Republic during thunderstorm activity. The angles of arrival (azimuth and elevation) were analyzed for selected distinct events. Comparisons of distances and azimuths of infrasound sources from the center of microbarometer array with lightning locations determined by EUCLID lightning detection network show that most of the selected events are most likely associated with intra-cloud (IC) discharges. Preceding rapid changes of electrostatic field, potential association of infrasound pulses with IC discharges, and high elevation angles of arrival for near infrasound sources indicate that an electrostatic mechanism is probably responsible for their generation. It is discussed that distinguishing of the relative role of thermal and electrostatic mechanism is difficult, and that none of published models of electrostatic production of infrasound thunder can explain the presented observations precisely. A modification of the current models, based on consideration of at least two charged layers is suggested. Further theoretical and experimental investigations are however needed to get a better description of the generation mechanism of those infrasound pulses.

Cysteine regulation of protein function--as exemplified by NMDA-receptor modulation.

PubMed

Lipton, Stuart A; Choi, Yun-Beom; Takahashi, Hiroto; Zhang, Dongxian; Li, Weizhong; Godzik, Adam; Bankston, Laurie A

2002-09-01

Until recently cysteine residues, especially those located extracellularly, were thought to be important for metal coordination, catalysis and protein structure by forming disulfide bonds - but they were not thought to regulate protein function. However, this is not the case. Crucial cysteine residues can be involved in modulation of protein activity and signaling events via other reactions of their thiol (sulfhydryl; -SH) groups. These reactions can take several forms, such as redox events (chemical reduction or oxidation), chelation of transition metals (chiefly Zn(2+), Mn(2+) and Cu(2+)) or S-nitrosylation [the catalyzed transfer of a nitric oxide (NO) group to a thiol group]. In several cases, these disparate reactions can compete with one another for the same thiol group on a single cysteine residue, forming a molecular switch composed of a latticework of possible redox, NO or Zn(2+) modifications to control protein function. Thiol-mediated regulation of protein function can also involve reactions of cysteine residues that affect ligand binding allosterically. This article reviews the basis for these molecular cysteine switches, drawing on the NMDA receptor as an exemplary protein, and proposes a molecular model for the action of S-nitrosylation based on recently derived crystal structures.

Discrete event performance prediction of speculatively parallel temperature-accelerated dynamics

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

Zamora, Richard James; Voter, Arthur F.; Perez, Danny

Due to its unrivaled ability to predict the dynamical evolution of interacting atoms, molecular dynamics (MD) is a widely used computational method in theoretical chemistry, physics, biology, and engineering. Despite its success, MD is only capable of modeling time scales within several orders of magnitude of thermal vibrations, leaving out many important phenomena that occur at slower rates. The Temperature Accelerated Dynamics (TAD) method overcomes this limitation by thermally accelerating the state-to-state evolution captured by MD. Due to the algorithmically complex nature of the serial TAD procedure, implementations have yet to improve performance by parallelizing the concurrent exploration of multiplemore » states. Here we utilize a discrete event-based application simulator to introduce and explore a new Speculatively Parallel TAD (SpecTAD) method. We investigate the SpecTAD algorithm, without a full-scale implementation, by constructing an application simulator proxy (SpecTADSim). Finally, following this method, we discover that a nontrivial relationship exists between the optimal SpecTAD parameter set and the number of CPU cores available at run-time. Furthermore, we find that a majority of the available SpecTAD boost can be achieved within an existing TAD application using relatively simple algorithm modifications.« less

Discrete event performance prediction of speculatively parallel temperature-accelerated dynamics

DOE PAGES

Zamora, Richard James; Voter, Arthur F.; Perez, Danny; ...

2016-12-01

Due to its unrivaled ability to predict the dynamical evolution of interacting atoms, molecular dynamics (MD) is a widely used computational method in theoretical chemistry, physics, biology, and engineering. Despite its success, MD is only capable of modeling time scales within several orders of magnitude of thermal vibrations, leaving out many important phenomena that occur at slower rates. The Temperature Accelerated Dynamics (TAD) method overcomes this limitation by thermally accelerating the state-to-state evolution captured by MD. Due to the algorithmically complex nature of the serial TAD procedure, implementations have yet to improve performance by parallelizing the concurrent exploration of multiplemore » states. Here we utilize a discrete event-based application simulator to introduce and explore a new Speculatively Parallel TAD (SpecTAD) method. We investigate the SpecTAD algorithm, without a full-scale implementation, by constructing an application simulator proxy (SpecTADSim). Finally, following this method, we discover that a nontrivial relationship exists between the optimal SpecTAD parameter set and the number of CPU cores available at run-time. Furthermore, we find that a majority of the available SpecTAD boost can be achieved within an existing TAD application using relatively simple algorithm modifications.« less

Genetic Control of the Secondary Modification of Deoxyribonucleic Acid in Escherichia coli1

PubMed Central

Mamelak, Linda; Boyer, Herbert W.

1970-01-01

The wild-type restriction and modification alleles of Escherichia coli K-12 and B were found to have no measurable effect on the patterns of methylated bases in the deoxyribonucleic acid (DNA) of these strains. The genetic region controlling the methylation of cytosine in E. coli K-12 was mapped close to his, and the presence or absence of this gene in E. coli B or E. coli K had no effect on the restriction and modification properties of these strains. Thus, only a few of the methylated bases in the DNA of these strains are involved in host modification, and the biological role of the remainder remains obscure. PMID:4919756

Quantitative site-specific reactivity profiling of S-nitrosylation in mouse skeletal muscle using cysteinyl peptide enrichment coupled with mass spectrometry

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

Su, Dian; Shukla, Anil K.; Chen, Baowei

2013-04-01

S-nitrosylation (SNO) is an important reversible thiol oxidation event that has been increasingly recognized for its role in cell signaling. While many proteins susceptible to S-nitrosylation have been reported, site-specific identification of physiologically relevant SNO modifications remains an analytical challenge due to the low-abundance and labile nature of the modification. Herein we present further improvement and optimization of the recently reported, resin-assisted cysteinyl peptide enrichment protocol for SNO identification and the extension of this application to mouse skeletal muscle to identify specific sites sensitive to S-nitrosylation by quantitative reactivity profiling. The results of our data indicate that the protein- andmore » peptide-level enrichment protocols provide comparable specificity and coverage of SNO-peptide identifications. S-nitrosylation reactivity profiling was performed by quantitatively comparing the site-specific SNO modification levels in samples treated with S-nitrosoglutathione (GSNO), an NO donor, at two different physiologically relevant concentrations (i.e., 10 μM and 100 μM). The reactivity profiling experiments overall identified 489 SNO-modified cysteine sites from 197 proteins with the specificity of 95.2% at the unique-peptide-level based on the percentage of Cys-peptides. Among these sites, 260 sites from 135 proteins were observed with relatively high reactivity to S-nitrosylation; such SNO-sensitive sites are more likely to be physiologically relevant. Many of the SNO-sensitive proteins are preferentially localized in mitochondria, contractile fiber and actin cytoskeleton, suggesting the susceptibility of these subcellular compartments to redox regulation. Moreover, the SNO-sensitive proteins seem to be primarily involved in metabolic pathways, including TCA cycle, glycolysis/gluconeogenesis, glutathione metabolism, and fatty acid metabolism, suggesting the importance of redox regulation in muscle metabolism and insulin action.« less

A weight modification sequential method for VSC-MTDC power system state estimation

NASA Astrophysics Data System (ADS)

Yang, Xiaonan; Zhang, Hao; Li, Qiang; Guo, Ziming; Zhao, Kun; Li, Xinpeng; Han, Feng

2017-06-01

This paper presents an effective sequential approach based on weight modification for VSC-MTDC power system state estimation, called weight modification sequential method. The proposed approach simplifies the AC/DC system state estimation algorithm through modifying the weight of state quantity to keep the matrix dimension constant. The weight modification sequential method can also make the VSC-MTDC system state estimation calculation results more ccurate and increase the speed of calculation. The effectiveness of the proposed weight modification sequential method is demonstrated and validated in modified IEEE 14 bus system.

Fear in the outdoor environment: description and modification through recreation programs

Treesearch

Alan Ewert; Anderson B. Young

1992-01-01

Using the Situational Fear Inventory, outdoor course participants identified the degree to which they experienced social-based and physical-based anxieties at the beginning, middle, end of their course. Levels of social-based fears were higher and more resistant to modification. Females expressed higher levels of fears. Most fears were reduced significantly through...

Beliefs about Child Support Modification Following Remarriage and Subsequent Childbirth

ERIC Educational Resources Information Center

Hans, Jason D.

2009-01-01

Framed by equity theory, fairness beliefs regarding child support modification to account for the financial impact of remarriage and subsequent childbirth were assessed. Based on a random sample of 407 Kentucky residents using a multiple segment factorial vignette approach, modification was supported by 57% of respondents following remarriage, but…

Novel mechanism for the modification of Al2O3-based inclusions in ultra-low carbon Al-killed steel considering the effects of magnesium and calcium

NASA Astrophysics Data System (ADS)

Guo, Jing; Cheng, Shu-sen; Guo, Han-jie; Mei, Ya-guang

2018-03-01

Many researchers have explored the inclusion modification mechanism to improve non-metallic inclusion modifications in steelmaking. In this study, two types of industrial trials on inclusion modifications in liquid steel were conducted using ultra-low-carbon Al-killed steel with different Mg and Ca contents to verify the effects of Ca and Mg contents on the modification mechanism of Al2O3-based inclusions during secondary refining. The results showed that Al2O3-based inclusions can be modified into liquid calcium aluminate or a multi-component inclusion with the addition of a suitable amount of Ca. In addition, [Mg] in liquid steel can further reduce CaO in liquid calcium aluminate to drive its evolution into CaO-MgO-Al2O3 multi-component inclusions. Thermodynamic analysis confirmed that the reaction between [Mg] and CaO in liquid calcium aluminate occurs when the MgO content of liquid calcium aluminate is less than 3wt% and the temperature is higher than 1843 K.

Real-time monitoring of single-photon detectors against eavesdropping in quantum key distribution systems.

PubMed

da Silva, Thiago Ferreira; Xavier, Guilherme B; Temporão, Guilherme P; von der Weid, Jean Pierre

2012-08-13

By employing real-time monitoring of single-photon avalanche photodiodes we demonstrate how two types of practical eavesdropping strategies, the after-gate and time-shift attacks, may be detected. Both attacks are identified with the detectors operating without any special modifications, making this proposal well suited for real-world applications. The monitoring system is based on accumulating statistics of the times between consecutive detection events, and extracting the afterpulse and overall efficiency of the detectors in real-time using mathematical models fit to the measured data. We are able to directly observe changes in the afterpulse probabilities generated from the after-gate and faint after-gate attacks, as well as different timing signatures in the time-shift attack. We also discuss the applicability of our scheme to other general blinding attacks.

Phytochemicals: A Multitargeted Approach to Gynecologic Cancer Therapy

PubMed Central

Oh, Se-Woong; Song, Yong Sang; Tsang, Benjamin K.

2014-01-01

Gynecologic cancers constitute the fourth most common cancer type in women. Treatment outcomes are dictated by a multitude of factors, including stage at diagnosis, tissue type, and overall health of the patient. Current therapeutic options include surgery, radiotherapy, and chemotherapy, although significant unmet medical needs remain in regard to side effects and long-term survival. The efficacy of chemotherapy is influenced by cellular events such as the overexpression of oncogenes and downregulation of tumor suppressors, which together determine apoptotic responses. Phytochemicals are a broad class of natural compounds derived from plants, a number of which exhibit useful bioactive effects toward these pathways. High-throughput screening methods, rational modification, and developments in regulatory policies will accelerate the development of novel therapeutics based on these compounds, which will likely improve overall survival and quality of life for patients. PMID:25093186

[Effective coverage to manage domestic violence against women in Mexican municipalities: limits of metrics].

PubMed

Viviescas-Vargas, Diana P; Idrovo, Alvaro Javier; López-López, Erika; Uicab-Pool, Gloria; Herrera-Trujillo, Mónica; Balam-Gómez, Maricela; Hidalgo-Solórzano, Elisa

2013-08-01

The study estimated the effective coverage of health services in primary care for the management of domestic violence against women in three municipalities in Mexico. We estimated the prevalence and severity of violence using a validated scale, and the effective coverage proposed by Shengelia and partners with any modifications. Quality care was considered when there was a suggestion to report it to authorities. The use and quality of care was low in the three municipalities analyzed, used most frequently when there was sexual or physical violence. Effective coverage was 29.41%, 16.67% and zero in Guachochi, Jojutla and Tizimín, respectively. The effective coverage indicator had difficulties in measuring events and responses that were not based on biomedical models. Findings suggest that the indicator can be improved by incorporating other dimensions of quality.

Implication of epigenetics in pancreas development and disease.

PubMed

Quilichini, Evans; Haumaitre, Cécile

2015-12-01

Pancreas development is controlled by a complex interaction of signaling pathways and transcription factor networks that determine pancreatic specification and differentiation of exocrine and endocrine cells. Epigenetics adds a new layer of gene regulation. DNA methylation, histone modifications and non-coding RNAs recently appeared as important epigenetic factors regulating pancreas development. In this review, we report recent findings obtained by analyses in model organisms as well as genome-wide approaches that demonstrate the role of these epigenetic regulators in the control of exocrine and endocrine cell differentiation, identity, function, proliferation and regeneration. We also highlight how altered epigenetic processes contribute to pancreatic disorders: diabetes and pancreatic cancer. Uncovering these epigenetic events can help to better understand these diseases, provide novel therapeutical targets for their treatment, and improve cell-based therapies for diabetes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Charged particle production in p+Pb collisions measured by the ATLAS detector

NASA Astrophysics Data System (ADS)

Shulga, Evgeny; ATLAS Collaboration

2017-01-01

Per-event charged particle spectra and nuclear modification factors are measured with the ATLAS detector at the LHC in p+Pb interactions at √sNN = 5.02 TeV. Results are presented as a function of transverse momentum, rapidity, and in different intervals of collision centrality, which is characterised in p+Pb collisions by the total transverse energy measured over the pseudorapidity interval -3.2 < η < -4.9 in the direction of the lead beam. Three different calculations of the number of nucleons participating in p+Pb collisions have been performed, assuming the Glauber model and its Glauber-Gribov Colour Fluctuation extensions. The results using different models are compared with each other, as well as with other measurements made under the same conditions and also with centrality definition based on different rapidity intervals.

Statistical Anomalies of Bitflips in SRAMs to Discriminate SBUs From MCUs

NASA Astrophysics Data System (ADS)

Clemente, Juan Antonio; Franco, Francisco J.; Villa, Francesca; Baylac, Maud; Rey, Solenne; Mecha, Hortensia; Agapito, Juan A.; Puchner, Helmut; Hubert, Guillaume; Velazco, Raoul

2016-08-01

Recently, the occurrence of multiple events in static tests has been investigated by checking the statistical distribution of the difference between the addresses of the words containing bitflips. That method has been successfully applied to Field Programmable Gate Arrays (FPGAs) and the original authors indicate that it is also valid for SRAMs. This paper presents a modified methodology that is based on checking the XORed addresses with bitflips, rather than on the difference. Irradiation tests on CMOS 130 & 90 nm SRAMs with 14-MeV neutrons have been performed to validate this methodology. Results in high-altitude environments are also presented and cross-checked with theoretical predictions. In addition, this methodology has also been used to detect modifications in the organization of said memories. Theoretical predictions have been validated with actual data provided by the manufacturer.

Modification of transparent materials with ultrashort laser pulses: What is energetically and mechanically meaningful?

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

Bulgakova, Nadezhda M., E-mail: nadezhda.bulgakova@hilase.cz; Institute of Thermophysics SB RAS, 1 Lavrentyev Ave., 630090 Novosibirsk; Zhukov, Vladimir P.

A comprehensive analysis of laser-induced modification of bulk glass by single ultrashort laser pulses is presented which is based on combination of optical Maxwell-based modeling with thermoelastoplastic simulations of post-irradiation behavior of matter. A controversial question on free electron density generated inside bulk glass by ultrashort laser pulses in modification regimes is addressed on energy balance grounds. Spatiotemporal dynamics of laser beam propagation in fused silica have been elucidated for the regimes used for direct laser writing in bulk glass. 3D thermoelastoplastic modeling of material relocation dynamics under laser-induced stresses has been performed up to the microsecond timescale when allmore » motions in the material decay. The final modification structure is found to be imprinted into material matrix already at sub-nanosecond timescale. Modeling results agree well with available experimental data on laser light transmission through the sample and the final modification structure.« less

GSK-3 mediates the okadaic acid-induced modification of collapsin response mediator protein-2 in human SK-N-SH neuroblastoma cells.

PubMed

Ni, Mei-Hui; Wu, Chih-Ching; Chan, Wen-Hsiung; Chien, Kun-Yi; Yu, Jau-Song

2008-04-15

Collapsin response mediator protein-2 (CRMP-2), a phosphoprotein involved in axonal outgrowth and microtubule dynamics, is aberrantly phosphorylated in Alzheimer's disease (AD) brain. Alteration of glycogen synthase kinase-3 (GSK-3) activity is associated with the pathogenesis of AD. Here, we show that CRMP-2 is one of the major substrates for GSK-3 in pig brain extracts. Both GSK-3alpha and 3beta phosphorylate purified pig brain CRMP-2 and significantly alter its mobility in SDS-gels, resembling the CRMP-2 modification observed in AD brain. Interestingly, this modification can be detected in SK-N-SH neuroblastoma cells treated with a phosphatase inhibitor, okadaic acid (OA), and GSK-3 inhibitors completely block this OA-induced event. Knockdown of both GSK-3alpha and 3beta, but not either kinase alone, impairs OA-induced modification of CRMP-2. Mutation of Ser-518 or Ser-522 of CRMP-2, which are highly phosphorylated in AD brain, to Ala blocks the OA-induced modification of CRMP-2 in SK-N-SH cells. Ser-522 prephosphorylated by Cdk5 is required for subsequent GSK-3alpha-mediated phosphorylation of CRMP-2 in vitro. Collectively, our results demonstrate for the first time that OA can induce phosphorylation of CRMP-2 in SK-N-SH cells at sites aberrantly phosphorylated in AD brain, and both GSK-3alpha and 3beta and Ser-522 kinase(s) are involved in this process.

Reduced or modified dietary fat for preventing cardiovascular disease

PubMed Central

Hooper, Lee; Summerbell, Carolyn D; Thompson, Rachel; Sills, Deirdre; Roberts, Felicia G; Moore, Helen; Smith, George Davey

2014-01-01

Background Reduction and modification of dietary fats have differing effects on cardiovascular risk factors (such as serum cholesterol), but their effects on important health outcomes are less clear. Objectives To assess the effect of reduction and/or modification of dietary fats on mortality, cardiovascular mortality, cardiovascular morbidity and individual outcomes including myocardial infarction, stroke and cancer diagnoses in randomised clinical trials of at least 6 months duration. Search methods For this review update, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, were searched through to June 2010. References of Included studies and reviews were also checked. Selection criteria Trials fulfilled the following criteria: 1) randomised with appropriate control group, 2) intention to reduce or modify fat or cholesterol intake (excluding exclusively omega-3 fat interventions), 3) not multi factorial, 4) adult humans with or without cardiovascular disease, 5) intervention at least six months, 6) mortality or cardiovascular morbidity data available. Data collection and analysis Participant numbers experiencing health outcomes in each arm were extracted independently in duplicate and random effects meta-analyses, meta-regression, sub-grouping, sensitivity analyses and funnel plots were performed. Main results This updated review suggested that reducing saturated fat by reducing and/or modifying dietary fat reduced the risk of cardiovascular events by 14% (RR 0.86, 95% CI 0.77 to 0.96, 24 comparisons, 65,508 participants of whom 7% had a cardiovascular event, I2 50%). Subgrouping suggested that this reduction in cardiovascular events was seen in studies of fat modification (not reduction - which related directly to the degree of effect on serum total and LDL cholesterol and triglycerides), of at least two years duration and in studies of men (not of women). There were no clear effects of dietary fat changes on total mortality (RR 0.98, 95% CI 0.93 to 1.04, 71,790 participants) or cardiovascular mortality (RR 0.94, 95% CI 0.85 to 1.04, 65,978 participants). This did not alter with sub-grouping or sensitivity analysis. Few studies compared reduced with modified fat diets, so direct comparison was not possible. Authors’ conclusions The findings are suggestive of a small but potentially important reduction in cardiovascular risk on modification of dietary fat, but not reduction of total fat, in longer trials. Lifestyle advice to all those at risk of cardiovascular disease and to lower risk population groups, should continue to include permanent reduction of dietary saturated fat and partial replacement by unsaturates. The ideal type of unsaturated fat is unclear. PMID:21735388

Protein arginine methylation: a prominent modification and its demethylation.

PubMed

Wesche, Juste; Kühn, Sarah; Kessler, Benedikt M; Salton, Maayan; Wolf, Alexander

2017-09-01

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.

Nutrition and prevention of Alzheimer’s dementia

PubMed Central

Swaminathan, Arun; Jicha, Gregory A.

2014-01-01

A nutritional approach to prevent, slow, or halt the progression of disease is a promising strategy that has been widely investigated. Much epidemiologic data suggests that nutritional intake may influence the development and progression of Alzheimer’s dementia (AD). Modifiable, environmental causes of AD include potential metabolic derangements caused by dietary insufficiency and or excess that may be corrected by nutritional supplementation and or dietary modification. Many nutritional supplements contain a myriad of health promoting constituents (anti-oxidants, vitamins, trace minerals, flavonoids, lipids, …etc.) that may have novel mechanisms of action affecting cellular health and regeneration, the aging process itself, or may specifically disrupt pathogenic pathways in the development of AD. Nutritional modifications have the advantage of being cost effective, easy to implement, socially acceptable and generally safe and devoid of significant adverse events in most cases. Many nutritional interventions have been studied and continue to be evaluated in hopes of finding a successful agent, combination of agents, or dietary modifications that can be used for the prevention and or treatment of AD. The current review focuses on several key nutritional compounds and dietary modifications that have been studied in humans, and further discusses the rationale underlying their potential utility for the prevention and treatment of AD. PMID:25368575

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives

PubMed Central

Zhang, Yan-Jiao; Li, Mu-Peng; Tang, Jie; Chen, Xiao-Ping

2017-01-01

Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel’s absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel. PMID:28335443

Base Release and Modification in Solid-Phase DNA Exposed to Low-Energy Electrons.

PubMed

Choofong, Surakarn; Cloutier, Pierre; Sanche, Léon; Wagner, J Richard

2016-11-01

Ionization generates a large number of secondary low-energy electrons (LEEs) with a most probable energy of approximately 10 eV, which can break DNA bonds by dissociative electron attachment (DEA) and lead to DNA damage. In this study, we investigated radiation damage to dry DNA induced by X rays (1.5 keV) alone on a glass substrate or X rays combined with extra LEEs (average energy of 5.8 eV) emitted from a tantalum (Ta) substrate under an atmosphere of N 2 and standard ambient conditions of temperature and pressure. The targets included calf-thymus DNA and double-stranded synthetic oligonucleotides. We developed analytical methods to measure the release of non-modified DNA bases from DNA and the formation of several base modifications by LC-MS/MS with isotopic dilution for precise quantification. The results show that the yield of non-modified bases as well as base modifications increase by 20-30% when DNA is deposited on a Ta substrate compared to that on a glass substrate. The order of base release (Gua > Ade > Thy ∼ Cyt) agrees well with several theoretical studies indicating that Gua is the most susceptible site toward sugar-phosphate cleavage. The formation of DNA damage by LEEs is explained by DEA leading to the release of non-modified bases involving the initial cleavage of N1-C1', C3'-O3' or C5'-O5' bonds. The yield of base modifications was lower than the release of non-modified bases. The main LEE-induced base modifications include 5,6-dihydrothymine (5,6-dHT), 5,6-dihydrouracil (5-dHU), 5-hydroxymethyluracil (5-HmU) and 5-formyluracil (5-ForU). The formation of base modifications by LEEs can be explained by DEA and cleavage of the C-H bond of the methyl group of Thy (giving 5-HmU and 5-ForU) and by secondary reactions of H atoms and hydride anions that are generated by primary LEE reactions followed by subsequent reaction with Cyt and Thy (giving 5,6-dHU and 5,6-dHT).

Capillary nano-immunoassays: advancing quantitative proteomics analysis, biomarker assessment, and molecular diagnostics.

PubMed

Chen, Jin-Qiu; Wakefield, Lalage M; Goldstein, David J

2015-06-06

There is an emerging demand for the use of molecular profiling to facilitate biomarker identification and development, and to stratify patients for more efficient treatment decisions with reduced adverse effects. In the past decade, great strides have been made to advance genomic, transcriptomic and proteomic approaches to address these demands. While there has been much progress with these large scale approaches, profiling at the protein level still faces challenges due to limitations in clinical sample size, poor reproducibility, unreliable quantitation, and lack of assay robustness. A novel automated capillary nano-immunoassay (CNIA) technology has been developed. This technology offers precise and accurate measurement of proteins and their post-translational modifications using either charge-based or size-based separation formats. The system not only uses ultralow nanogram levels of protein but also allows multi-analyte analysis using a parallel single-analyte format for increased sensitivity and specificity. The high sensitivity and excellent reproducibility of this technology make it particularly powerful for analysis of clinical samples. Furthermore, the system can distinguish and detect specific protein post-translational modifications that conventional Western blot and other immunoassays cannot easily capture. This review will summarize and evaluate the latest progress to optimize the CNIA system for comprehensive, quantitative protein and signaling event characterization. It will also discuss how the technology has been successfully applied in both discovery research and clinical studies, for signaling pathway dissection, proteomic biomarker assessment, targeted treatment evaluation and quantitative proteomic analysis. Lastly, a comparison of this novel system with other conventional immuno-assay platforms is performed.

In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays

PubMed Central

Soldà, Giulia; Merlino, Giuseppe; Fina, Emanuela; Brini, Elena; Moles, Anna; Cappelletti, Vera; Daidone, Maria Grazia

2016-01-01

Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment. PMID:26556871

Thermal events documented in Hadean zircons by ion microprobe depth profiles

NASA Astrophysics Data System (ADS)

Trail, Dustin; Mojzsis, Stephen J.; Harrison, T. Mark

2007-08-01

We report the first U-Th-Pb ion microprobe depth profiles of four Hadean zircons from the Jack Hills and Mount Narryer supracrustal belts of the Narryer Gneiss Complex (NGC), Western Australia. This ultra-high spatial resolution technique probes the age and origin of sub-micron features in individual crystals that can record episodes of zircon growth. Near-surface grain dates of 2700 Ma or older are coincident with post-depositional growth/modification. Some ages may coincide with documented pre-deposition metamorphic events for the NGC and igneous emplacement at ca. 3700 Ma. Separate events that do not correlate in time with known geologic episodes prior to the preserved rock record are also present on pre-4000 Ma zircons. We find evidence for a ˜3.9 Ga event, which is coterminous within age uncertainty with one or several large basin-forming impacts (e.g. Nectaris) on the Moon attributed to the late heavy bombardment of the inner solar system.

Lactose-modified DNA tile nanostructures as drug carriers.

PubMed

Akkus Sut, Pinar; Tunc, Cansu Umran; Culha, Mustafa

2016-09-01

DNA hybridization allows the preparation of nanoscale DNA structures with desired shape and size. DNA structures using simple base pairing can be used for the delivery of drug molecules into the cells. Since DNA carries multiple negative charges, their cellular uptake efficiency is low. Thus, the modification of the DNA structures with molecules that may enhance the cellular internalization may be an option. The objective of this study is to construct DNA-based nanocarrier system and to investigate the cellular uptake of DNA tile with/without lactose modification. Doxorubicin was intercalated to DNA tile and cellular uptake of drug-loaded DNA-based carrier with/without lactose modification was investigated in vitro. HeLa, BT-474, and MDA-MB-231 cancer cells were used for cellular uptake studies and cytotoxicity assays. Using fluorescence spectroscopy, flow cytometry, and confocal microscopy, cellular uptake behavior of DNA tile was investigated. The cytotoxicity of DNA tile structures was determined with WST-1 assay. The results show that modification with lactose effectively increases the intracellular uptake of doxorubicin loaded DNA tile structure by cancer cells compared with the unmodified DNA tile. The findings of this study suggest that DNA-based nanostructures modified with carbohydrates can be used as suitable multifunctional nanocarriers with simple chemical modifications.

Influence of plasma modification on hygienic properties of textile fabrics with nonporous membrane coating

NASA Astrophysics Data System (ADS)

Voznesensky, E. F.; Ibragimov, R. G.; Vishnevskaya, O. V.; Sisoev, V. A.; Lutfullina, G. G.; Tihonova, N. V.

2017-11-01

The work investigated the possibility of using plasma modification to improve the hygienic properties of textile materials with nonporous membrane coating to improve vapor-, air-permeability and water-resistant. Determined that, after plasma modification changes degree of supramolecular orderliness of the polymers nonporous membrane coating and the base fabric.

Influence of major-groove chemical modifications of DNA on transcription by bacterial RNA polymerases.

PubMed

Raindlová, Veronika; Janoušková, Martina; Slavíčková, Michaela; Perlíková, Pavla; Boháčová, Soňa; Milisavljevič, Nemanja; Šanderová, Hana; Benda, Martin; Barvík, Ivan; Krásný, Libor; Hocek, Michal

2016-04-20

DNA templates containing a set of base modifications in the major groove (5-substituted pyrimidines or 7-substituted 7-deazapurines bearing H, methyl, vinyl, ethynyl or phenyl groups) were prepared by PCR using the corresponding base-modified 2'-deoxyribonucleoside triphosphates (dNTPs). The modified templates were used in an in vitro transcription assay using RNA polymerase from Bacillus subtilis and Escherichia coli Some modified nucleobases bearing smaller modifications (H, Me in 7-deazapurines) were perfectly tolerated by both enzymes, whereas bulky modifications (Ph at any nucleobase) and, surprisingly, uracil blocked transcription. Some middle-sized modifications (vinyl or ethynyl) were partly tolerated mostly by the E. colienzyme. In all cases where the transcription proceeded, full length RNA product with correct sequence was obtained indicating that the modifications of the template are not mutagenic and the inhibition is probably at the stage of initiation. The results are promising for the development of bioorthogonal reactions for artificial chemical switching of the transcription. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Effects of Computer-Based Training on Procedural Modifications to Standard Functional Analyses

ERIC Educational Resources Information Center

Schnell, Lauren K.; Sidener, Tina M.; DeBar, Ruth M.; Vladescu, Jason C.; Kahng, SungWoo

2018-01-01

Few studies have evaluated methods for training decision-making when functional analysis data are undifferentiated. The current study evaluated computer-based training to teach 20 graduate students to arrange functional analysis conditions, analyze functional analysis data, and implement procedural modifications. Participants were exposed to…

Two Student Self-Management Techniques Applied to Data-Based Program Modification.

ERIC Educational Resources Information Center

Wesson, Caren

Two student self-management techniques, student charting and student selection of instructional activities, were applied to ongoing data-based program modification. Forty-two elementary school resource room students were assigned randomly (within teacher) to one of three treatment conditions: Teacher Chart-Teacher Select Instructional Activities…

Model-based meta-analysis to evaluate optimal doses of direct oral factor Xa inhibitors in atrial fibrillation patients

PubMed Central

Yoshioka, Hideki; Sato, Hiromi; Hatakeyama, Hiroto

2018-01-01

The noninferiority of direct oral factor Xa (FXa) inhibitors (rivaroxaban, apixaban, and edoxaban) in treatment of atrial fibrillation were demonstrated compared with warfarin by several large clinical trials; however, subsequent meta-analyses reported a higher risk of major bleeding with rivaroxaban than with the other FXa inhibitors. In the present study, we first estimated the changes of prothrombin time (PT) in 5 randomized trials based on reported population pharmacokinetic and pharmacodynamic models and then carried out a model-based meta-analysis to obtain models describing the relationship between PT changes and the event rates of ischemic stroke/systemic embolism (SE) and of major bleeding. By using the models, we simulated the optimal therapeutic doses for each FXa inhibitor. It was suggested that dose reduction of rivaroxaban from the current 20 mg/d to 10 mg/d would decrease patient deaths from major bleeding (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.64-0.74) with little increase in those for ischemic stroke/SE (HR, 1.11; 95% CI, 1.07-1.20). The overall decrease in the mortality caused by both events was estimated as 5.81 per 10 000 patient-years (95% CI, 3.92-8.16), with an HR of 0.87 (95% CI, 0.83-0.91). For apixaban and edoxaban, no distinct change in the overall mortality was simulated by dose modification. This study suggested that the current dose of rivaroxaban might be excessive and would need to be reduced to decrease the excess risk of major bleeding. PMID:29760204

High-Value, Cost-Conscious Care: Iterative Systems-Based Interventions to Reduce Unnecessary Laboratory Testing.

PubMed

Sadowski, Brett W; Lane, Alison B; Wood, Shannon M; Robinson, Sara L; Kim, Chin Hee

2017-09-01

Inappropriate testing contributes to soaring healthcare costs within the United States, and teaching hospitals are vulnerable to providing care largely for academic development. Via its "Choosing Wisely" campaign, the American Board of Internal Medicine recommends avoiding repetitive testing for stable inpatients. We designed systems-based interventions to reduce laboratory orders for patients admitted to the wards at an academic facility. We identified the computer-based order entry system as an appropriate target for sustainable intervention. The admission order set had allowed multiple routine tests to be ordered repetitively each day. Our iterative study included interventions on the automated order set and cost displays at order entry. The primary outcome was number of routine tests controlled for inpatient days compared with the preceding year. Secondary outcomes included cost savings, delays in care, and adverse events. Data were collected over a 2-month period following interventions in sequential years and compared with the year prior. The first intervention led to 0.97 fewer laboratory tests per inpatient day (19.4%). The second intervention led to sustained reduction, although by less of a margin than order set modifications alone (15.3%). When extrapolating the results utilizing fees from the Centers for Medicare and Medicaid Services, there was a cost savings of $290,000 over 2 years. Qualitative survey data did not suggest an increase in care delays or near-miss events. This series of interventions targeting unnecessary testing demonstrated a sustained reduction in the number of routine tests ordered, without adverse effects on clinical care. Published by Elsevier Inc.

Experience with Adaptive Security Policies.

DTIC Science & Technology

1998-03-01

3.1 Introduction r: 3.2 Logical Groupings of audited permission checks 29 3.3 Auditing of system servers via microkernel snooping 31 3.4...performed by servers other than the microkernel . Since altering each server to audit events would complicate the integration of new servers, a...modification to the microkernel was implemented to allow the microkernel to audit the requests made of other servers. Both methods for enhancing audit

20 CFR 668.750 - Under what circumstances can we or the INA grantee modify the terms of the grantee's plan(s)?

Code of Federal Regulations, 2010 CFR

2010-04-01

... the INA grantee's plan to add funds or, if required by Congressional action, to reduce the amount of funds available for expenditure. (b) The INA grantee may request approval to modify its plan to add... event that further clarification or modification is required, we may extend the thirty (30) day time...

20 CFR 668.750 - Under what circumstances can we or the INA grantee modify the terms of the grantee's plan(s)?

Code of Federal Regulations, 2011 CFR

2011-04-01

... the INA grantee's plan to add funds or, if required by Congressional action, to reduce the amount of funds available for expenditure. (b) The INA grantee may request approval to modify its plan to add... event that further clarification or modification is required, we may extend the thirty (30) day time...

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

Walton, B.T.; Ho, C.H.; Ma, C.Y.

Morphological abnormalities including extra compound eyes, extra heads, and distally duplicated legs were generated in cricket embryos by treating eggs with single doses of either benz(g)isoquinoline-5,10-dione or benzo(h)quinoline-5,6-dione. Slight structural modifications of the molecules resulted in a loss of teratogenic activity, although embryotoxicity occurred. These potent insect teratogens can be used for analysis of developmental events during embryogenesis. 13 references, 4 figures, 1 table.

Epigenetic Regulation of Myeloid Cells

PubMed Central

IVASHKIV, LIONEL B.; PARK, SUNG HO

2017-01-01

Epigenetic regulation in myeloid cells is crucial for cell differentiation and activation in response to developmental and environmental cues. Epigenetic control involves posttranslational modification of DNA or chromatin, and is also coupled to upstream signaling pathways and transcription factors. In this review, we summarize key epigenetic events and how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation, and innate immune memory. PMID:27337441

Design and Modification of an Installation Method to Stabilize Small Trapezoidal Flumes in Drainage Ditches

Treesearch

Charles A. Harrison; Susan O’Ney

2002-01-01

We developed procedures for installing prefabricated trapezoidal flumes in deep (10 to 12 feet) drainage ditches to monitor hydrologic functions and provide gauge locations for sampling discharge. Flows from the instrumented basins were generally low, but the ditches were occasionally subject to high flows caused by rain events of 2 to 3 inches or more. These high flow...

78 FR 41425 - In the Matter of Duke Energy Carolinas, LLC; (Oconee Nuclear Station, Units 1, 2, and 3...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

... SSF diesel generator during a fire for which the SSF is credited. This modification along with... SSF equipment in the event of a failure of the SSF diesel generator during a fire for which the SSF is... provide water to the steam generators of all three units sufficient to remove decay heat following...

Technical Modification Within the Healthcare Industry: Improving Both the Efficacy of the National Drug Code Carrier and the Accessibility of Electronic Health Records to Reduce Adverse Drug Events

DTIC Science & Technology

2013-06-01

with an EHR .................................................. 97 C. SWOT ANALYSIS OF USING QR CODES WITH THE NDC AND WITH EHRS...96 Figure 41. SWOT analysis ................................................................................... 99 xiii LIST OF...Coordinator for Health Information Technology OTC Over-the-Counter PHI Personal Health Information QR Quick Response SWOT Strengths, Weaknesses

Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

PubMed

Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

2015-01-01

Of critical importance to many of the events underlying transcriptional control of gene expression are modifications to core and linker histones that regulate the accessibility of trans-acting factors to the DNA substrate within the context of chromatin. Likewise, control over the initiation of DNA replication, as well as the ability of the replication machinery to proceed during elongation through the multiple levels of chromatin condensation that are likely to be encountered, is known to involve the creation of chromatin accessibility. In the latter case, chromatin access will likely need to be a transient event so as to prevent total genomic unraveling of the chromatin that would be deleterious to cells. While there are many molecular and biochemical approaches in use to study histone changes and their relationship to transcription and chromatin accessibility, few techniques exist that allow a molecular dissection of the events underlying DNA replication control as it pertains to chromatin changes and accessibility. Here, we outline a novel experimental strategy for addressing the ability of specific proteins to induce large-scale chromatin unfolding (decondensation) in vivo upon site-specific targeting to an engineered locus. Our laboratory has used this powerful system in novel ways to directly address the ability of DNA replication proteins to create chromatin accessibility, and have incorporated modifications to the basic approach that allow for a molecular genetic analysis of the mechanisms and associated factors involved in causing chromatin decondensation by a protein of interest. Alternative approaches involving co-expression of other proteins (competitors or stimulators), concurrent drug treatments, and analysis of co-localizing histone modifications are also addressed, all of which are illustrative of the utility of this experimental system for extending basic findings to physiologically relevant mechanisms. Although used by our group to analyze mechanisms underlying DNA replication associated chromatin accessibility, this unique and powerful experimental system has the propensity to be a valuable tool for understanding chromatin remodeling mechanisms orchestrated by other cellular processes such as DNA repair, recombination, mitotic chromosome condensation, or other chromosome dynamics involving chromatin alterations and accessibility.

Climate change and predicting soil loss from rainfall

NASA Astrophysics Data System (ADS)

Kinnell, Peter

2017-04-01

Conceptually, rainfall has a certain capacity to cause soil loss from an eroding area while soil surfaces have a certain resistance to being eroded by rainfall. The terms "rainfall erosivity' and "soil erodibility" are frequently used to encapsulate the concept and in the Revised Universal Soil Loss Equation (RUSLE), the most widely used soil loss prediction equation in the world, average annual values of the R "erosivity" factor and the K "erodibility" factor provide a basis for accounting for variation in rainfall erosion associated with geographic variations of climate and soils. In many applications of RUSLE, R and K are considered to be independent but in reality they are not. In RUSLE2, provision has been made to take account of the fact that K values determined using soil physical factors have to be adjusted for variations in climate because runoff is not directly included as a factor in determining R. Also, the USLE event erosivity index EI30 is better related to accounting for event sediment concentration than event soil loss. While the USLE-M, a modification of the USLE which includes runoff as a factor in determining the event erosivity index provides better estimates of event soil loss when event runoff is known, runoff prediction provides a challenge to modelling event soil loss as climate changes

The use of a medical dictionary for regulatory activities terminology (MedDRA) in prescription-event monitoring in Japan (J-PEM).

PubMed

Yokotsuka, M; Aoyama, M; Kubota, K

2000-07-01

The Medical Dictionary for Regulatory Activities Terminology (MedDRA) version 2.1 (V2.1) was released in March 1999 accompanied by the MedDRA/J V2.1J specifically for Japanese users. In prescription-event monitoring in Japan (J-PEM), we have employed the MedDRA/J for data entry, signal generation and event listing. In J-PEM, the lowest level terms (LLTs) in the MedDRA/J are used in data entry because the richness of LLTs is judged to be advantageous. A signal is generated normally at the preferred term (PT) level, but it has been found that various reporters describe the same event using descriptions that are potentially encoded by LLTs under different PTs. In addition, some PTs are considered too specific to generate the proper signal. In the system used in J-PEM, when an LLT is selected as a candidate to encode an event, another LLT under a different PT, if any, is displayed on the computer screen so that it may be coded instead of, or in addition to, the candidate LLT. The five-level structure of the MedDRA is used when listing events but some modification is required to generate a functional event list.

The role of SUMOylation in ageing and senescent decline.

PubMed

Princz, Andrea; Tavernarakis, Nektarios

2017-03-01

Posttranslational protein modifications are playing crucial roles in essential cellular mechanisms. SUMOylation is a reversible posttranslational modification of specific target proteins by the attachment of a small ubiquitin-like protein. Although the mechanism of conjugation of SUMO to proteins is analogous to ubiquitination, it requires its own, specific set of enzymes. The consequences of SUMOylation are widely variable, depending on the physiological state of the cell and the attached SUMO isoform. Accumulating recent findings have revealed a prominent role of SUMOylation in molecular pathways that govern senescence and ageing. Here, we review the link between SUMO attachment events and cellular processes that influence senescence and ageing, including promyelocytic leukaemia (PML) nuclear body and telomere function, autophagy, reactive oxygen species (ROS) homeostasis and growth factor signalling. Copyright © 2017 Elsevier B.V. All rights reserved.

Akt3 is a privileged first responder in isozyme-specific electrophile response.

PubMed

Long, Marcus J C; Parvez, Saba; Zhao, Yi; Surya, Sanjna L; Wang, Yiran; Zhang, Sheng; Aye, Yimon

2017-03-01

Isozyme-specific post-translational regulation fine tunes signaling events. However, redundancy in sequence or activity renders links between isozyme-specific modifications and downstream functions uncertain. Methods to study this phenomenon are underdeveloped. Here we use a redox-targeting screen to reveal that Akt3 is a first-responding isozyme sensing native electrophilic lipids. Electrophile modification of Akt3 modulated downstream pathway responses in cells and Danio rerio (zebrafish) and markedly differed from Akt2-specific oxidative regulation. Digest MS sequencing identified Akt3 C119 as the privileged cysteine that senses 4-hydroxynonenal. A C119S Akt3 mutant was hypomorphic for all downstream phenotypes shown by wild-type Akt3. This study documents isozyme-specific and chemical redox signal-personalized physiological responses.

Health Benefits of Fasting and Caloric Restriction.

PubMed

Golbidi, Saeid; Daiber, Andreas; Korac, Bato; Li, Huige; Essop, M Faadiel; Laher, Ismail

2017-10-23

Obesity and obesity-related diseases, largely resulting from urbanization and behavioral changes, are now of global importance. Energy restriction, though, is associated with health improvements and increased longevity. We review some important mechanisms related to calorie limitation aimed at controlling of metabolic diseases, particularly diabetes. Calorie restriction triggers a complex series of intricate events, including activation of cellular stress response elements, improved autophagy, modification of apoptosis, and alteration in hormonal balance. Intermittent fasting is not only more acceptable to patients, but it also prevents some of the adverse effects of chronic calorie restriction, especially malnutrition. There are many somatic and potentially psychologic benefits of fasting or intermittent calorie restriction. However, some behavioral modifications related to abstinence of binge eating following a fasting period are crucial in maintaining the desired favorable outcomes.

Catabolism of native and oxidized low density lipoproteins: in vivo insights from small animal positron emission tomography studies.

PubMed

Pietzsch, J; Bergmann, R; Wuest, F; Pawelke, B; Hultsch, C; van den Hoff, J

2005-12-01

The human organism is exposed to numerous processes that generate reactive oxygen species (ROS). ROS may directly or indirectly cause oxidative modification and damage of proteins. Protein oxidation is regarded as a crucial event in the pathogenesis of various diseases ranging from rheumatoid arthritis to Alzheimer's disease and atherosclerosis. As a representative example, oxidation of low density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Data concerning the role of circulating oxidized LDL (oxLDL) in the development and outcome of diseases are scarce. One reason for this is the shortage of methods for direct assessment of the metabolic fate of circulating oxLDL in vivo. We present an improved methodology based on the radiolabelling of apoB-100 of native LDL (nLDL) and oxLDL, respectively, with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). Radiolabelling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively, in vitro. The method was further evaluated with respect to the radiopharmacological properties of both [(18)F]fluorobenzoylated nLDL and oxLDL by biodistribution studies in male Wistar rats. The metabolic fate of [(18)F]fluorobenzoylated nLDL and oxLDL in rats in vivo was further delineated by dynamic positron emission tomography (PET) using a dedicated small animal tomograph (spatial resolution of 2 mm). From this study we conclude that the use of [(18)F]FB-labelled LDL particles is an attractive alternative to, e.g., LDL iodination methods, and is of value to characterize and to discriminate the kinetics and the metabolic fate of nLDL and oxLDL in small animals in vivo.

Coherent Doppler Lidar for Boundary Layer Studies and Wind Energy

NASA Astrophysics Data System (ADS)

Choukulkar, Aditya

This thesis outlines the development of a vector retrieval technique, based on data assimilation, for a coherent Doppler LIDAR (Light Detection and Ranging). A detailed analysis of the Optimal Interpolation (OI) technique for vector retrieval is presented. Through several modifications to the OI technique, it is shown that the modified technique results in significant improvement in velocity retrieval accuracy. These modifications include changes to innovation covariance portioning, covariance binning, and analysis increment calculation. It is observed that the modified technique is able to make retrievals with better accuracy, preserves local information better, and compares well with tower measurements. In order to study the error of representativeness and vector retrieval error, a lidar simulator was constructed. Using the lidar simulator a thorough sensitivity analysis of the lidar measurement process and vector retrieval is carried out. The error of representativeness as a function of scales of motion and sensitivity of vector retrieval to look angle is quantified. Using the modified OI technique, study of nocturnal flow in Owens' Valley, CA was carried out to identify and understand uncharacteristic events on the night of March 27th 2006. Observations from 1030 UTC to 1230 UTC (0230 hr local time to 0430 hr local time) on March 27 2006 are presented. Lidar observations show complex and uncharacteristic flows such as sudden bursts of westerly cross-valley wind mixing with the dominant up-valley wind. Model results from Coupled Ocean/Atmosphere Mesoscale Prediction System (COAMPS RTM) and other in-situ instrumentations are used to corroborate and complement these observations. The modified OI technique is used to identify uncharacteristic and extreme flow events at a wind development site. Estimates of turbulence and shear from this technique are compared to tower measurements. A formulation for equivalent wind speed in the presence of variations in wind speed and direction, combined with shear is developed and used to determine wind energy content in presence of turbulence.

Study adaptation, design, and methods of a web-based PTSD intervention for women Veterans.

PubMed

Lehavot, Keren; Litz, Brett; Millard, Steven P; Hamilton, Alison B; Sadler, Anne; Simpson, Tracy

2017-02-01

Women Veterans are a rapidly growing population with high risk of exposure to potentially traumatizing events and PTSD diagnoses. Despite the dissemination of evidence-based treatments for PTSD in the VA, most women Veteran VA users underutilize these treatments. Web-based PTSD treatment has the potential to reach and engage women Veterans with PTSD who do not receive treatment in VA settings. Our objective is to modify and evaluate Delivery of Self Training and Education for Stressful Situations (DESTRESSS), a web-based cognitive-behavioral intervention for PTSD, to target PTSD symptoms among women Veterans. The specific aims are to: (1) obtain feedback about DESTRESS, particularly on its relevance and sensitivity to women, using semi-structured interviews with expert clinicians and women Veterans with PTSD, and make modifications based on this feedback; (2) conduct a pilot study to finalize study procedures and make further refinements to the intervention; and (3) conduct a randomized clinical trial (RCT) evaluating a revised, telephone-assisted DESTRESS compared to telephone monitoring only. We describe the results from the first two aims, and the study design and procedures for the ongoing RCT. This line of research has the potential to result in a gender-sensitive, empirically-based, online treatment option for women Veterans with PTSD. Published by Elsevier Inc.

Facilitating Follow-up of LIGO-Virgo Events Using Rapid Sky Localization

NASA Astrophysics Data System (ADS)

Chen, Hsin-Yu; Holz, Daniel E.

2017-05-01

We discuss an algorithm for accurate and very low-latency (<1 s) localization of gravitational-wave (GW) sources using only the relative times of arrival, relative phases, and relative signal-to-noise ratios for pairs of detectors. The algorithm is independent of distances and masses to leading order, and can be generalized to all discrete (as opposed to stochastic and continuous) sources detected by ground-based detector networks. Our approach is similar to that of BAYESTAR with a few modifications, which result in increased computational efficiency. For the LIGO two-detector configuration (Hanford+Livingston) operating in O1 we find a median 50% (90%) localization of 143 deg2 (558 deg2) for binary neutron stars. We use our algorithm to explore the improvement in localization resulting from loud events, finding that the loudest out of the first 4 (or 10) events reduces the median sky-localization area by a factor of 1.9 (3.0) for the case of two GW detectors, and 2.2 (4.0) for three detectors. We also consider the case of multi-messenger joint detections in both the gravitational and the electromagnetic radiation, and show that joint localization can offer significant improvements (e.g., in the case of LIGO and Fermi/GBM joint detections). We show that a prior on the binary inclination, potentially arising from GRB observations, has a negligible effect on GW localization. Our algorithm is simple, fast, and accurate, and may be of particular utility in the development of multi-messenger astronomy.

The Impact of Bariatric Surgery on Type 2 Diabetes Mellitus and the Management of Hypoglycemic Events

PubMed Central

Kassem, Mahmoud Attia Mohamed; Durda, Michael Andrew; Stoicea, Nicoleta; Cavus, Omer; Sahin, Levent; Rogers, Barbara

2017-01-01

Recent studies discussed the benefit of bariatric surgery on obese patients diagnosed with type 2 diabetes mellitus (T2DM). Several factors play an essential role in predicting the impact of bariatric surgery on T2DM, such as ABCD score (age, BMI, C-peptide, and duration of the disease), HbA1c, and fasting blood glucose, incretins [glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (GIP)]. DiaRem score known to include factors such as age, HbA1c, medication, and insulin usage used to predict the remission of T2DM, but it has some limitations. An extensive literature search was conducted on PubMed and Google Scholar using keywords such as gastric bypass, T2DM, bariatric surgery, GLP-1, GIP, and post bariatric hypoglycemia. Restrictive-malabsorptive procedures are most effective in treating T2DM patients based on changes induced in appetite through regulation of gastrointestinal hormones, with decreased hunger and increased satiation. We provide a review of bariatric surgery influence on T2DM and management of post-intervention hypoglycemic events. Post-bariatric surgery hypoglycemia is a serious complication especially when patients develop life-threatening neuroglycopenia with loss of consciousness and seizure. The avoidance of this adverse event may be achieved by strict dietary modification including a restriction on carbohydrates as well as foods with high glycemic index. Further research will provide more information on post-bariatric surgery hyperinsulinemic hypoglycemia pathophysiology and management. PMID:28298900

Perturbed threat monitoring following a traumatic event predicts risk for post-traumatic stress disorder.

PubMed

Naim, R; Wald, I; Lior, A; Pine, D S; Fox, N A; Sheppes, G; Halpern, P; Bar-Haim, Y

2014-07-01

Post-traumatic stress disorder (PTSD) is a chronic and difficult to treat psychiatric disorder. Objective, performance-based diagnostic markers that uniquely index risk for PTSD above and beyond subjective self-report markers could inform attempts to improve prevention and early intervention. We evaluated the predictive value of threat-related attention bias measured immediately after a potentially traumatic event, as a risk marker for PTSD at a 3-month follow-up. We measured the predictive contribution of attentional threat bias above and beyond that of the more established marker of risk for PTSD, self-reported psychological dissociation. Dissociation symptoms and threat-related attention bias were measured in 577 motor vehicle accident (MVA) survivors (mean age = 35.02 years, 356 males) within 24 h of admission to an emergency department (ED) of a large urban hospital. PTSD symptoms were assessed at a 3-month follow-up using the Clinician-Administered PTSD Scale (CAPS). Self-reported dissociation symptoms significantly accounted for 16% of the variance in PTSD at follow-up, and attention bias toward threat significantly accounted for an additional 4% of the variance in PTSD. Threat-related attention bias can be reliably measured in the context of a hospital ED and significantly predicts risk for later PTSD. Possible mechanisms underlying the association between threat bias following a potentially traumatic event and risk for PTSD are discussed. The potential application of an attention bias modification treatment (ABMT) tailored to reduce risk for PTSD is suggested.

More than genes: the advanced fetal programming hypothesis.

PubMed

Hocher, Berthold

2014-10-01

Many lines of data, initial epidemiologic studies as well as subsequent extensive experimental studies, indicate that early-life events play a powerful role in influencing later suceptibility to certain chronic diseases. Such events might be over- or undernutrition, exposure to environmental toxins, but also changes in hormones, in particular stress hormones. Typically, those events are triggered by the environmental challenges of the mother. However, recent studies have shown that paternal environmental or nutritional factors affect the phenotype of the offspring as well. The maternal and paternal environmental factors act on the phenotype of the offspring via epigenetic modification of its genome. The advanced fetal programming hypothesis proposes an additional non-environmentally driven mechanism: maternal and also paternal genes may influence the maturating sperm, the oocyte, and later the embryo/fetus, leading to their epigenetic alteration. Thus, the observed phenotype of the offspring may be altered by maternal/paternal genes independent of the fetal genome. Meanwhile, several independent association studies in humans dealing with metabolic and neurological traits also suggest that maternal genes might affect the offspring phenotype independent of the transmission of that particular gene to the offspring. Considering the implications of this hypothesis, some conclusions drawn from transgenic or knockout animal models and based on the causality between a genetic alteration and a phenotype, need to be challenged. Possible implications for the development, diagnostic and therapy of human genetic diseases have to be investigated. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Support Vector Machine Model for Automatic Detection and Classification of Seismic Events

NASA Astrophysics Data System (ADS)

Barros, Vesna; Barros, Lucas

2016-04-01

The automated processing of multiple seismic signals to detect, localize and classify seismic events is a central tool in both natural hazards monitoring and nuclear treaty verification. However, false detections and missed detections caused by station noise and incorrect classification of arrivals are still an issue and the events are often unclassified or poorly classified. Thus, machine learning techniques can be used in automatic processing for classifying the huge database of seismic recordings and provide more confidence in the final output. Applied in the context of the International Monitoring System (IMS) - a global sensor network developed for the Comprehensive Nuclear-Test-Ban Treaty (CTBT) - we propose a fully automatic method for seismic event detection and classification based on a supervised pattern recognition technique called the Support Vector Machine (SVM). According to Kortström et al., 2015, the advantages of using SVM are handleability of large number of features and effectiveness in high dimensional spaces. Our objective is to detect seismic events from one IMS seismic station located in an area of high seismicity and mining activity and classify them as earthquakes or quarry blasts. It is expected to create a flexible and easily adjustable SVM method that can be applied in different regions and datasets. Taken a step further, accurate results for seismic stations could lead to a modification of the model and its parameters to make it applicable to other waveform technologies used to monitor nuclear explosions such as infrasound and hydroacoustic waveforms. As an authorized user, we have direct access to all IMS data and bulletins through a secure signatory account. A set of significant seismic waveforms containing different types of events (e.g. earthquake, quarry blasts) and noise is being analysed to train the model and learn the typical pattern of the signal from these events. Moreover, comparing the performance of the support-vector network to various classical learning algorithms used before in seismic detection and classification is an essential final step to analyze the advantages and disadvantages of the model.

Immunochemical approach to the problem of differential determination of natural forms of abscisic acid.

PubMed

Blintsov, A N; Gussakovskaya, M A

2004-10-01

An original modification of the standard ELISA procedure for differential determination of different forms of abscisic acid (ABA) is proposed. It is shown that endogenous forms of ABA may be quantitatively determined in plant tissues subjected to minimal treatment, without purification of the hormones and their chemical modification. The modification has been approved when analyzing changes in the content of different ABA forms in plant tissues differing in physiological activity. Quantitative differential determination of changes in the content of different ABA forms has been performed in ovaries of Triticum aestivum L. and Taraxacum officinale Web. in the period of activity of the ovule (from the moment of its activation to the beginning of division). It is shown that, despite the different types of reproduction in the species studied (amphimixis and apomixis), the time course of changes in the content of different forms of ABA in ovaries is similar, which is suggestive of a correlation between the activity of endogenous hormonal system and chronology of main events (e.g., the beginning of endospermogenesis) of the reproductive cycle.

The discrete Fourier transform algorithm for determining decay constants—Implementation using a field programmable gate array

NASA Astrophysics Data System (ADS)

Bostrom, G.; Atkinson, D.; Rice, A.

2015-04-01

Cavity ringdown spectroscopy (CRDS) uses the exponential decay constant of light exiting a high-finesse resonance cavity to determine analyte concentration, typically via absorption. We present a high-throughput data acquisition system that determines the decay constant in near real time using the discrete Fourier transform algorithm on a field programmable gate array (FPGA). A commercially available, high-speed, high-resolution, analog-to-digital converter evaluation board system is used as the platform for the system, after minor hardware and software modifications. The system outputs decay constants at maximum rate of 4.4 kHz using an 8192-point fast Fourier transform by processing the intensity decay signal between ringdown events. We present the details of the system, including the modifications required to adapt the evaluation board to accurately process the exponential waveform. We also demonstrate the performance of the system, both stand-alone and incorporated into our existing CRDS system. Details of FPGA, microcontroller, and circuitry modifications are provided in the Appendix and computer code is available upon request from the authors.

Modulating peroxisome proliferator–activated receptors for therapeutic benefit? Biology, clinical experience, and future prospects

PubMed Central

Rosenson, Robert S.; Wright, R. Scott; Farkouh, Michael; Plutzky, Jorge

2014-01-01

Clinical trials of cardiovascular disease (CVD) prevention in patients with type 2 diabetes mellitus primarily have been directed at the modification of a single major risk factor; however, in trials that enroll patients with and without diabetes, the absolute risk in CVD events remains higher in patients with diabetes. Efforts to reduce the macrovascular and microvascular residual risk have been directed toward a multifactorial CVD risk-factor modification; nonetheless, long-term complications remain high. Dual-peroxisome proliferator–activated receptor (PPAR) α/γ agonists may offer opportunities to lower macrovascular and microvascular complications of type 2 diabetes mellitus beyond the reductions achieved with conventional risk-factor modification. The information presented elucidates the differentiation of compound-specific vs class-effect properties of PPARs as the basis for future development of a new candidate molecule. Prior experience with thiazolidinediones, an approved class of PPARγ agonists, and glitazars, investigational class of dual-PPARα/γ agonists, also provides important lessons about the risks and benefits of targeting a nuclear receptor while revealing some of the future challenges for regulatory approval. PMID:23137497

Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus.

PubMed

Rezaei-Ghaleh, Nasrollah; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

2016-07-29

Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The small-x gluon distribution in centrality biased pA and pp collisions

NASA Astrophysics Data System (ADS)

Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

2018-06-01

The nuclear modification factor RpA (pT) provides information on the small-x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small-x gluons. We find that the biased nuclear modification factor QpA (pT) for central collisions is above RpA (pT) for minimum bias events, and that it may redevelop a "Cronin peak" even at small x. The magnitude of the peak is predicted to increase approximately like 1 /A⊥ ν, ν ∼ 0.6 ± 0.1, if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A⊥. We predict an enhanced Qpp (pT) - 1 ∼ 1 /(pT2) ν and a Cronin peak even for central pp collisions.

Dynamic ubiquitin signaling in cell cycle regulation

PubMed Central

Gilberto, Samuel

2017-01-01

The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. PMID:28684425

Dynamic ubiquitin signaling in cell cycle regulation.

PubMed

Gilberto, Samuel; Peter, Matthias

2017-08-07

The cell division cycle is driven by a collection of enzymes that coordinate DNA duplication and separation, ensuring that genomic information is faithfully and perpetually maintained. The activity of the effector proteins that perform and coordinate these biological processes oscillates by regulated expression and/or posttranslational modifications. Ubiquitylation is a cardinal cellular modification and is long known for driving cell cycle transitions. In this review, we emphasize emerging concepts of how ubiquitylation brings the necessary dynamicity and plasticity that underlie the processes of DNA replication and mitosis. New studies, often focusing on the regulation of chromosomal proteins like DNA polymerases or kinetochore kinases, are demonstrating that ubiquitylation is a versatile modification that can be used to fine-tune these cell cycle events, frequently through processes that do not involve proteasomal degradation. Understanding how the increasing variety of identified ubiquitin signals are transduced will allow us to develop a deeper mechanistic perception of how the multiple factors come together to faithfully propagate genomic information. Here, we discuss these and additional conceptual challenges that are currently under study toward understanding how ubiquitin governs cell cycle regulation. © 2017 Gilberto and Peter.

Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.

PubMed

Gomes, A S; Alves, R N; Rønnestad, I; Power, D M

2015-09-01

Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified. Copyright © 2014 Elsevier Inc. All rights reserved.

Precipitation chemistry of Lhasa and other remote towns, Tibet

NASA Astrophysics Data System (ADS)

Zhang, David D.; Peart, Mervyn; Jim, C. Y.; He, Y. Q.; Li, B. S.; Chen, J. A.

Precipitation event samples during 1987-1988 field expedition periods and 1997, 1998, 1999 and 2000 have been collected at Lhasa, Dingri, Dangxiong and Amdo, Tibet. The sampling and analysis were based on WMO recommendations for a background network with some modifications according to local conditions and environmental characteristics. The following precipitation constituents and related parameters were measured: pH, conductivity, CO 2 partial pressure, total suspended particles, and the content of K +, Na +, Ca 2+, Mg 2+, Fe, Mn, NH 4+, Cl -, NO 2-, NO 3-, SO42- Br-, HCO 3- and HPO 42-. Some atmospheric dust samples have also been collected. Over 300 precipitation events have been measured for pH and conductivity. Among these, 60 have been analysed for their chemical components. The results show that Lhasa's precipitation events were constantly alkaline with weighted averages of pH 8.36 in the 1987-1988 period, and 7.5 for 1997 to 1999. Only one event was weakly acidic during 1997-1999. Although CO 2 partial pressure, a major producer of acidity in natural water on the Plateau, falls with increasing elevation, the lowest measured CO 2 partial pressure can only raise pH value by 0.1 units in the sampling areas. Chemical analysis indicates that the major contributor to alkaline precipitation is the continental dust, which is rich in calcium. The analysis also shows that Tibet is still one of the cleanest areas in the world with little air pollution. However, the decline of pH from the 1980s to 1990s, which was reflected by an increase of NO 3- and SO 42- in precipitation, alerts us to the urgency of environmental protection in this fragile paradise.

Event-related cerebral hemodynamics reveal target-specific resource allocation for both "go" and "no-go" response-based vigilance tasks.

PubMed

Shaw, Tyler H; Funke, Matthew E; Dillard, Michael; Funke, Gregory J; Warm, Joel S; Parasuraman, Raja

2013-08-01

Transcranial Doppler sonography was used to measure cerebral blood flow velocity (CBFV) in the right and left cerebral hemispheres during the performance of a 50-min visual vigilance session. Observers monitored a simulated flight of unmanned aerial vehicles for cases in which one of the vehicles was flying in an inappropriate direction relative to its cohorts. Two types of vigilance tasks were employed: a traditional task in which observers made button press ("go") responses to critical signals, and a modification of the traditional task called the Sustained Attention to Response Task (SART) in which "go" responses acknowledged nonsignal events and response withholding ("no-go") signified signal detection. Signal detections and global CBFV scores declined over time. In addition, fine-grained event-related analyses revealed that the detection of signals was accompanied by an elevation of CBFV that was not present with missed signals. As was the case with the global scores, the magnitude of the transient CBFV increments associated with signal detection also declined over time, and these findings were independent of task type. The results support the view of CBFV as an index of the cognitive evaluation of stimulus significance, and a resource model of vigilance in which the need for continuous attention produces a depletion of information-processing assets that are not replenished as the task progresses. Further, temporal declines in the magnitude of event-related CBFV in response to critical signals only is evidence that the decrement function in vigilance is due to attentional processing and not specific task elements such as the required response format. Copyright © 2013. Published by Elsevier Inc.

Focused process improvement events: sustainability of impact on process and performance in an academic radiology department.

PubMed

Rosenkrantz, Andrew B; Lawson, Kirk; Ally, Rosina; Chen, David; Donno, Frank; Rittberg, Steven; Rodriguez, Joan; Recht, Michael P

2015-01-01

To evaluate sustainability of impact of rapid, focused process improvement (PI) events on process and performance within an academic radiology department. Our department conducted PI during 2011 and 2012 in CT, MRI, ultrasound, breast imaging, and research billing. PI entailed participation by all stakeholders, facilitation by the department chair, collection of baseline data, meetings during several weeks, definition of performance metrics, creation of an improvement plan, and prompt implementation. We explore common themes among PI events regarding initial impact and durability of changes. We also assess performance in each area pre-PI, immediately post-PI, and at the time of the current study. All PI events achieved an immediate improvement in performance metrics, often entailing both examination volumes and on-time performance. IT-based solutions, process standardization, and redefinition of staff responsibilities were often central in these changes, and participants consistently expressed improved internal leadership and problem-solving ability. Major environmental changes commonly occurred after PI, including a natural disaster with equipment loss, a change in location or services offered, and new enterprise-wide electronic medical record system incorporating new billing and radiology informatics systems, requiring flexibility in the PI implementation plan. Only one PI team conducted regular post-PI follow-up meetings. Sustained improvement was frequently, but not universally, observed: in the long-term following initial PI, measures of examination volume showed continued progressive improvements, whereas measures of operational efficiency remained stable or occasionally declined. Focused PI is generally effective in achieving performance improvement, although a changing environment influences the sustainability of impact. Thus, continued process evaluation and ongoing workflow modifications are warranted. Copyright © 2015 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Management of ceritinib therapy and adverse events in patients with ALK-rearranged non-small cell lung cancer.

PubMed

Califano, Raffaele; Greystoke, Alastair; Lal, Rohit; Thompson, Joyce; Popat, Sanjay

2017-09-01

Anaplastic lymphoma kinase rearrangement (ALK+) occurs in approximately 2-7% of patients with non-small cell lung cancer (NSCLC), contributing to a considerable number of patients with ALK+ NSCLC worldwide. Ceritinib is a next generation ALK inhibitor (ALKi), approved by the European Medicines Agency in 2015. In the first-in-human, phase I study, ceritinib demonstrated rapid and durable responses in ALK patients previously treated with a different ALKi and in those who were ALKi-naive. As ceritinib is starting to be used routinely for the treatment of patients with ALK+ NSCLC, experience is growing with regard to ideal therapy management. In this review we provide a brief background to the development of ceritinib. The optimal treatment management and adverse events associated with ceritinib in clinical trials and in clinical practice are then discussed in detail, and where applicable, an expert consensus on specific recommendations are made. In clinical trials, the most common adverse events related to ceritinib are nausea, vomiting, and diarrhea. However, the majority of these are mild and, in the opinion of the authors, can be effectively managed with dose modifications. Based on clinical data, ceritinib has demonstrated efficacy as a first-line therapy and in patients who have relapsed on crizotinib, including those with brain metastases at baseline. Unfortunately, at some point, all patients experience progressive disease, with the central nervous system being a common site of metastases. Recommendations are made for continuing treatment beyond disease progression as long as a clinical benefit to patients is observed. Here, we review management of ceritinib treatment and adverse events and make recommendations on optimal management of patients. Copyright © 2017. Published by Elsevier B.V.

Game-Based Approaches, Pedagogical Principles and Tactical Constraints: Examining Games Modification

ERIC Educational Resources Information Center

Serra-Olivares, Jaime; García-López, Luis M.; Calderón, Antonio

2016-01-01

The purpose of this study was to analyze the effect of modification strategies based on the pedagogical principles of the Teaching Games for Understanding approach on tactical constraints of four 3v3 soccer small-sided games. The Game performance of 21 U-10 players was analyzed in a game similar to the adult game; one based on keeping-the-ball;…

Study on the Modifications Required to Re-Engine the Lockheed D-21 Drone

NASA Technical Reports Server (NTRS)

1999-01-01

This report was prepared by Lockheed Martin (LM). The purpose of this 45 day study contract was to investigate the feasibility of using the D-21 as a Rocket Based Combined Cycle engine test-bed. The new NASA engine is entitled "Demonstration of Rocket Combined Cycle Operations (DRACO)". Four objectives were defined and modification study provide an estimation of the: (1) mudified vehicle performance; (2) required engine performance; (3) required vehicle modification; and (4) modification cost and schedule.

Forging Ahead through Darkness: PCNA, Still the Principal Conductor at the Replication Fork.

PubMed

Choe, Katherine N; Moldovan, George-Lucian

2017-02-02

Proliferating cell nuclear antigen (PCNA) lies at the center of the faithful duplication of eukaryotic genomes. With its distinctive doughnut-shaped molecular structure, PCNA was originally studied for its role in stimulating DNA polymerases. However, we now know that PCNA does much more than promote processive DNA synthesis. Because of the complexity of the events involved, cellular DNA replication poses major threats to genomic integrity. Whatever predicament lies ahead for the replication fork, PCNA is there to orchestrate the events necessary to handle it. Through its many protein interactions and various post-translational modifications, PCNA has far-reaching impacts on a myriad of cellular functions. Copyright © 2017 Elsevier Inc. All rights reserved.

Current practices in the management of adverse events associated with targeted therapies for advanced renal cell carcinoma: a national survey of oncologists.

PubMed

Ruiz, Janelle Nicole; Belum, Viswanath Reddy; Creel, Patricia; Cohn, Allen; Ewer, Michael; Lacouture, Mario E

2014-10-01

Oncologists treating patients with targeted therapies encounter adverse events (AEs) that pose management challenges, lead to dosing inconsistencies, and impact patient quality of life. Oncologists' practices and attitudes in the management of targeted therapy-related AEs in patients with renal cell carcinoma (RCC) are poorly understood. We sought to identify unmet needs associated with AE management and understand oncologists' treatment optimization strategies. A 24-item online survey was administered in August 2012 to 119 US oncologists treating patients with advanced RCC. The survey solicited responses regarding demographics, practice settings, AE management practice patterns and beliefs, treatment barriers, and patient education. Respondents indicated that between 25% and 50% of patients require dose modification/discontinuation because of AEs. The greatest barrier to optimizing treatment for RCC is the unpredictability of patient responses to treatment (43%). Most respondents (78%) discuss AE management with patients, but only a minority of them proactively reach out to patients (46%). Most practitioners (70%) refer patients to nononcology specialists when faced with unfamiliar AEs, although finding interested physicians (43%) and time constraints (40%) were the most commonly cited barriers to consulting with other specialties. Results suggest that many patients require dose modification/discontinuation because of AEs and that nononcologists are a frequently utilized resource to manage these events. There is a need for predictive drug toxicity markers to establish counseling and prevention, along with opportunities for increased education on supportive care techniques to maintain health-related quality of life and consistent dosing. Copyright © 2014 Elsevier Inc. All rights reserved.

Laser-Based Surface Modification of Microstructure for Carbon Fiber-Reinforced Plastics

NASA Astrophysics Data System (ADS)

Yang, Wenfeng; Sun, Ting; Cao, Yu; Li, Shaolong; Liu, Chang; Tang, Qingru

2018-05-01

Bonding repair is a powerful feature of carbon fiber-reinforced plastics (CFRP). Based on the theory of interface bonding, the interface adhesion strength and reliability of the CFRP structure will be directly affected by the microscopic features of the CFRP surface, including the microstructure, physical, and chemical characteristics. In this paper, laser-based surface modification was compared to Peel-ply, grinding, and polishing to comparatively evaluate the surface microstructure of CFRP. The surface microstructure, morphology, fiber damage, height and space parameters were investigated by scanning electron microscopy (SEM) and laser confocal microscopy (LCM). Relative to the conventional grinding process, laser modification of the CFRP surface can result in more uniform resin removal and better processing control and repeatability. This decreases the adverse impact of surface fiber fractures and secondary damage. The surface properties were significantly optimized, which has been reflected such things as the obvious improvement of surface roughness, microstructure uniformity, and actual area. The improved surface microstructure based on laser modification is more conducive to interface bonding of CFRP structure repair. This can enhance the interfacial adhesion strength and reliability of repair.

Liganded and unliganded activation of estrogen receptor and hormone replacement therapies

PubMed Central

Maggi, Adriana

2011-01-01

Over the past two decades, our understanding of estrogen receptor physiology in mammals widened considerably as we acquired a deeper appreciation of the roles of estrogen receptor alpha and beta (ERα and ERβ) in reproduction as well as in bone and metabolic homeostasis, depression, vascular disorders, neurodegenerative diseases and cancer. In addition, our insights on ER transcriptional functions in cells increased considerably with the demonstration that ER activity is not strictly dependent on ligand availability. Indeed, unliganded ERs may be transcriptionally active and post-translational modifications play a major role in this context. The finding that several intracellular transduction molecules may regulate ER transcriptional programs indicates that ERs may act as a hub where several molecular pathways converge: this allows to maintain ER transcriptional activity in tune with all cell functions. Likely, the biological relevant role of ER was favored by evolution as a mean of integration between reproductive and metabolic functions. We here review the post-translational modifications modulating ER transcriptional activity in the presence or in the absence of estrogens and underline their potential role for ER tissue-specific activities. In our opinion, a better comprehension of the variety of molecular events that control ER activity in reproductive and non-reproductive organs is the foundation for the design of safer and more efficacious hormone-based therapies, particularly for menopause. PMID:21605666

Effects of Ionizing Radiation on Biological Molecules—Mechanisms of Damage and Emerging Methods of Detection

PubMed Central

Reisz, Julie A.; Bansal, Nidhi; Qian, Jiang; Zhao, Weiling

2014-01-01

Abstract Significance: The detrimental effects of ionizing radiation (IR) involve a highly orchestrated series of events that are amplified by endogenous signaling and culminating in oxidative damage to DNA, lipids, proteins, and many metabolites. Despite the global impact of IR, the molecular mechanisms underlying tissue damage reveal that many biomolecules are chemoselectively modified by IR. Recent Advances: The development of high-throughput “omics” technologies for mapping DNA and protein modifications have revolutionized the study of IR effects on biological systems. Studies in cells, tissues, and biological fluids are used to identify molecular features or biomarkers of IR exposure and response and the molecular mechanisms that regulate their expression or synthesis. Critical Issues: In this review, chemical mechanisms are described for IR-induced modifications of biomolecules along with methods for their detection. Included with the detection methods are crucial experimental considerations and caveats for their use. Additional factors critical to the cellular response to radiation, including alterations in protein expression, metabolomics, and epigenetic factors, are also discussed. Future Directions: Throughout the review, the synergy of combined “omics” technologies such as genomics and epigenomics, proteomics, and metabolomics is highlighted. These are anticipated to lead to new hypotheses to understand IR effects on biological systems and improve IR-based therapies. Antioxid. Redox Signal. 21: 260–292. PMID:24382094

Potential sensitivity of warm season precipitation to urbanization extents: Modeling study in Beijing-Tianjin-Hebei urban agglomeration in China

NASA Astrophysics Data System (ADS)

Wang, Jun; Feng, Jinming; Yan, Zhongwei

2015-09-01

In this study, we investigated how different degrees of urbanization affect local and regional rainfall using high-resolution simulations based on the Weather Research and Forecasting Model. The extreme rainfall event of 21 July 2012 in Beijing was simulated for three representative urban land use distributions (no urbanization, early urbanization level of 1980, and recent urbanization level of 2009). Results suggest that urban modification of rainfall is potentially sensitive to urban land use condition. Rainfall was increased significantly over the downwind Beijing metropolis because of the effects of early urbanization; however, recent conditions of high urban development caused no significant increase. Further comparative analysis revealed that positive urban thermodynamical effects (i.e., urban warming, increased sensible heat transportation, and enhanced convergence and vertical motions) play major roles in urban modification of rainfall during the early urbanization stage. However, after cities expand to a certain extent (i.e., urban agglomeration), the regional moisture depression induced by the prevalence of impervious urban land has an effect on atmospheric instability energy, which might negate the city's positive impact on regional rainfall. Additional results from regional climate simulations for 10 Julys confirm this supposition. Given the explosive urban population growth and increasing demand for freshwater in cities, the potential negative effects of the urban environment on precipitation are worth investigation, particularly in rapidly developing countries and regions.

Recent developments of post-modification of biochar for electrochemical energy storage.

PubMed

Cheng, Bin-Hai; Zeng, Raymond J; Jiang, Hong

2017-12-01

Biochar is a common byproduct from thermochemical conversion of biomass to produce bioenergy. However, the biochar features, such as morphology, porosity and surface chemistry, cannot be well controlled in conventional conversion approaches, limiting the wide application of raw biochar. Aiming to meet the specific requirements, post-modification of raw biochar was frequently conducted to improve the quality. In this review, recent developments regarding post-modification methods of biochar are presented and discussed. Progresses on the applications of post modified biochar as electrode materials for supercapacitors are intensively summarized. This review aims to reveal the key factors that affecting the performance of biochar-based supercapacitors, and provide guidance for rationalizing the modification methods to expand the applications of biochar-based functional materials in supercapacitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Utilization Patterns of Lipid-lowering Therapies in Patients With Atherosclerotic Cardiovascular Disease or Diabetes: A Population-based Study in South Korea.

PubMed

Kim, Siin; Kim, Hyungtae; Kim, Eunju; Han, Sola; Rane, Pratik P; Fox, Kathleen M; Zhao, Zhongyun; Qian, Yi; Suh, Hae Sun

2018-06-01

We aimed to study the utilization patterns of lipid-lowering treatment (LLT), including treatment modification, adherence, and possible statin intolerance, in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes using national claims data in South Korea. A retrospective cohort study was conducted using data from the Korean Health Insurance Review & Assessment Service claims database. Patients aged ≥18 years with >1 outpatient pharmacy claim for a statin and/or ezetimibe dated January 1, 2012, to December 31, 2014, were identified and categorized into the following cohorts: patients with ASCVD, and patients with diabetes mellitus without ASCVD. LLT modification, adherence to index LLT, and possible statin intolerance were explored during the 12 months after the date of first prescription for a statin and/or ezetimibe. Among 1,399,872 patients who met the eligibility criteria, 807,547 (57.7%) were patients with ASCVD and 592,325 (42.3%) were patients with diabetes without ASCVD. About half of the patients had no modification in their index treatment (46.2% in the ASCVD cohort and 48.9% in the diabetes cohort), and the most common modification was permanent discontinuation (19.6% in the ASCVD cohort and 21.4% in the diabetes cohort). The mean medication possession ratios were 0.77 in the ASCVD cohort and 0.73 in the diabetes cohort and showed a decreasing trend during the 12-month follow-up period. Among patients who initiated a statin and/or ezetimibe, possible statin intolerance was observed in 53,921 patients (6.7%) in the ASCVD cohort and 42,172 patients (7.1%) in the diabetes cohort. In South Korea, a high rate of permanent discontinuation of statin therapy in patients with ASCVD or diabetes places these patients at high risk for cardiovascular events in the future. A decreasing trend of adherence to LLT implies that more intensive education and management are required to improve therapeutic effect and reduce the risk for ASCVD. The high rate of possible statin intolerance highlights an unmet need in the prevention and management of ASCVD in South Korea. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

A study of parton fragmentation in hadronic Z 0 decays using Λ Λ correlations

NASA Astrophysics Data System (ADS)

OPAL Collaboration; Abbiendi, G.; et al.

2000-03-01

The correlated production of Λ and Λ baryons has been studied using 4.3 million multihadronic Z0 decays recorded with the Opal detector at Lep. Lambda pairs were investigated in the full data sample and for the first time also in 2-jet and 3-jet events selected with the k⊥ algorithm. The distributions of rapidity differences from correlated Λ Λ pairs exhibit short-range, local correlations and prove to be a sensitive tool to test models, particularly for 2-jet events. The Jetset model describes the data best but some extra parameter tuning is needed to improve agreement with the experimental results in the rates and the rapidity spectra simultaneously. The recently developed modification of Jetset, the MOdified Popcorn Scenarium (Mops), and also Herwig do not give satisfactory results. This study of di-lambda production in 2- and 3-jet events supports the short-range compensation of quantum numbers.

Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

DOE PAGES

Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

2018-02-02

The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

L-Area STS MTR/NRU/NRX Grapple Assembly Closure Mechanics Review

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

Huizenga, D. J.

2016-06-08

A review of the closure mechanics associated with the Shielded Transfer System (STS) MTR/NRU/NRX grapple assembly utilized at the Savannah River Site (SRS) was performed. This review was prompted by an operational event which occurred at the Canadian Nuclear Laboratories (CNL) utilizing a DTS-XL grapple assembly which is essentially identical to the STS MTR/NRU/NRX grapple assembly used at the SRS. The CNL operational event occurred when a NRU/NRX fuel basket containing spent nuclear fuel assemblies was inadvertently released by the DTS-XL grapple assembly during a transfer. The SM review of the STS MTR/NRU/NRX grapple assembly will examine the operational aspectsmore » of the STS and the engineered features of the STS which prevent such an event at the SRS. The design requirements for the STS NRU/NRX modifications and the overall layout of the STS are provided in other documents.« less

Dynamic event tree analysis with the SAS4A/SASSYS-1 safety analysis code

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

Jankovsky, Zachary K.; Denman, Matthew R.; Aldemir, Tunc

The consequences of a transient in an advanced sodium-cooled fast reactor are difficult to capture with the traditional approach to probabilistic risk assessment (PRA). Numerous safety-relevant systems are passive and may have operational states that cannot be represented by binary success or failure. In addition, the specific order and timing of events may be crucial which necessitates the use of dynamic PRA tools such as ADAPT. The modifications to the SAS4A/SASSYS-1 sodium-cooled fast reactor safety analysis code for linking it to ADAPT to perform a dynamic PRA are described. A test case is used to demonstrate the linking process andmore » to illustrate the type of insights that may be gained with this process. Finally, newly-developed dynamic importance measures are used to assess the significance of reactor parameters/constituents on calculated consequences of initiating events.« less

Physics, chemistry and pulmonary sequelae of thermodegradation events in long-mission space flight

NASA Technical Reports Server (NTRS)

Todd, Paul; Sklar, Michael; Ramirez, W. Fred; Smith, Gerald J.; Morgenthaler, George W.; Oberdoerster, Guenter

1993-01-01

An event in which electronic insulation consisting of polytetrafluoroethylene undergoes thermodegradation on the Space Station Freedom is considered experimentally and theoretically from the initial chemistry and convective transport through pulmonary deposition in humans. The low-gravity enviroment impacts various stages of event simulation. Vapor-phase and particulate thermodegradation products were considered as potential spacecraft contaminants. A potential pathway for the production of ultrafine particles was identified. Different approaches to the simulation and prediction of contaminant transport were studied and used to predict the distribution of generic vapor-phase products in a Space Station model. A lung transport model was used to assess the pulmonary distribution of inhaled particles, and, finally, the impact of adaptation to low gravity on the human response to this inhalation risk was explored on the basis of known physiological modifications of the immune, endocrine, musculoskeletal and pulmonary systems that accompany space flight.

Measurement of z boson transverse momentum in proton - anti-proton collisions at √s = 1.96 TeV

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

Wang, Lei

This dissertation describes a measurement of the shape of the boson transverse momentum distribution in pmore » $$\\bar{p}$$ → Z/γ* → e +e - + X events at a center-of-mass energy of 1.96 TeV. The measurement is made for events with electron-positron mass between 70 < M ee < 110 GeV/c 2 and uses 976 pb -1 of data collected at the Fermilab Tevatron collider with the D0 detector. The shape is measured both for the inclusive sample and for the subset of events containing a boson with large rapidity. The large-rapidity distribution shows better agreement with theory when the calculation is done using traditional Collins-Soper-Sterman resummation than when using a recent resummed form factor with modifications in the small-x region.« less

Creatinine-Based and Cystatin C-Based GFR Estimating Equations and Their Non-GFR Determinants in Kidney Transplant Recipients.

PubMed

Keddis, Mira T; Amer, Hatem; Voskoboev, Nikolay; Kremers, Walter K; Rule, Andrew D; Lieske, John C

2016-09-07

eGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors. A cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined. Median measured GFR was 55.0 ml/min per 1.73 m(2). eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by -13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by -8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C. Thus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR. Copyright © 2016 by the American Society of Nephrology.

Prediction of novel families of enzymes involved in oxidative and other complex modifications of bases in nucleic acids.

PubMed

Iyer, Lakshminarayan M; Tahiliani, Mamta; Rao, Anjana; Aravind, L

2009-06-01

Modified bases in nucleic acids present a layer of information that directs biological function over and beyond the coding capacity of the conventional bases. While a large number of modified bases have been identified, many of the enzymes generating them still remain to be discovered. Recently, members of the 2-oxoglutarate- and iron(II)-dependent dioxygenase super-family, which modify diverse substrates from small molecules to biopolymers, were predicted and subsequently confirmed to catalyze oxidative modification of bases in nucleic acids. Of these, two distinct families, namely the AlkB and the kinetoplastid base J binding proteins (JBP) catalyze in situ hydroxylation of bases in nucleic acids. Using sensitive computational analysis of sequences, structures and contextual information from genomic structure and protein domain architectures, we report five distinct families of 2-oxoglutarate- and iron(II)-dependent dioxygenase that we predict to be involved in nucleic acid modifications. Among the DNA-modifying families, we show that the dioxygenase domains of the kinetoplastid base J-binding proteins belong to a larger family that includes the Tet proteins, prototyped by the human oncogene Tet1, and proteins from basidiomycete fungi, chlorophyte algae, heterolobosean amoeboflagellates and bacteriophages. We present evidence that some of these proteins are likely to be involved in oxidative modification of the 5-methyl group of cytosine leading to the formation of 5-hydroxymethylcytosine. The Tet/JBP homologs from basidiomycete fungi such as Laccaria and Coprinopsis show large lineage-specific expansions and a tight linkage with genes encoding a novel and distinct family of predicted transposases, and a member of the Maelstrom-like HMG family. We propose that these fungal members are part of a mobile transposon. To the best of our knowledge, this is the first report of a eukaryotic transposable element that encodes its own DNA-modification enzyme with a potential regulatory role. Through a wider analysis of other poorly characterized DNA-modifying enzymes we also show that the phage Mu Mom-like proteins, which catalyze the N6-carbamoylmethylation of adenines, are also linked to diverse families of bacterial transposases, suggesting that DNA modification by transposable elements might have a more general presence than previously appreciated. Among the other families of 2-oxoglutarate- and iron(II)-dependent dioxygenases identified in this study, one which is found in algae, is predicted to mainly comprise of RNA-modifying enzymes and shows a striking diversity in protein domain architectures suggesting the presence of RNA modifications with possibly unique adaptive roles. The results presented here are likely to provide the means for future investigation of unexpected epigenetic modifications, such as hydroxymethyl cytosine, that could profoundly impact our understanding of gene regulation and processes such as DNA demethylation.

Biochar modification to enhance sorption of inorganics from water.

PubMed

Sizmur, Tom; Fresno, Teresa; Akgül, Gökçen; Frost, Harrison; Moreno-Jiménez, Eduardo

2017-12-01

Biochar can be used as a sorbent to remove inorganic pollutants from water but the efficiency of sorption can be improved by activation or modification. This review evaluates various methods to increase the sorption efficiency of biochar including activation with steam, acids and bases and the production of biochar-based composites with metal oxides, carbonaceous materials, clays, organic compounds, and biofilms. We describe the approaches, and explain how each modification alters the sorption capacity. Physical and chemical activation enhances the surface area or functionality of biochar, whereas modification to produce biochar-based composites uses the biochar as a scaffold to embed new materials to create surfaces with novel surface properties upon which inorganic pollutants can sorb. Many of these approaches enhance the retention of a wide range of inorganic pollutants in waters, but here we provide a comparative assessment for Cd 2+ , Cu 2+ , Hg 2+ , Pb 2+ , Zn 2+ , NH 4 + , NO 3 - , PO 4 3- , CrO 4 2- and AsO 4 3- . Copyright © 2017 Elsevier Ltd. All rights reserved.

Overcoming environmental deterioration through defensive expenditures: field evidence from Bahía del Tóbari (Sonora, México) and implications for coastal impact assessment.

PubMed

Escofet, A; Bravo-Peña, L C

2007-08-01

The costs of the maneuvers that fishermen and shrimp farmers have to undertake in a coastal scenario where both the access to navigable waters and water quality have decreased were interpreted as defensive expenditures. Maneuvers were prompted by profound changes in water circulation and siltation mode imposed by major shifts in regional and local land-use patterns. In coastal scenarios under heavy land-based discharges and local geomorphic modifications, local users with little chance to move away may modify their routines in order to maintain existing levels of utility. The concept of defensive expenditures could be used to assess social responses to adverse changes in environmental and resource conditions, as a means to distinguish stages in which local sectors respond individually from qualitatively different stages in which intersectoral events are more conspicuous.

Identification of novel direct protein-protein interactions by irradiating living cells with femtosecond UV laser pulses.

PubMed

Itri, Francesco; Monti, Daria Maria; Chino, Marco; Vinciguerra, Roberto; Altucci, Carlo; Lombardi, Angela; Piccoli, Renata; Birolo, Leila; Arciello, Angela

2017-10-07

The identification of protein-protein interaction networks in living cells is becoming increasingly fundamental to elucidate main biological processes and to understand disease molecular bases on a system-wide level. We recently described a method (LUCK, Laser UV Cross-linKing) to cross-link interacting protein surfaces in living cells by UV laser irradiation. By using this innovative methodology, that does not require any protein modification or cell engineering, here we demonstrate that, upon UV laser irradiation of HeLa cells, a direct interaction between GAPDH and alpha-enolase was "frozen" by a cross-linking event. We validated the occurrence of this direct interaction by co-immunoprecipitation and Immuno-FRET analyses. This represents a proof of principle of the LUCK capability to reveal direct protein interactions in their physiological environment. Copyright © 2017 Elsevier Inc. All rights reserved.

Managing hypertension in type 2 diabetes mellitus.

PubMed

Horr, Samuel; Nissen, Steven

2016-06-01

Hypertension is a common problem in the diabetic population with estimates suggesting a prevalence exceeding 60%. Comorbid hypertension and diabetes mellitus are associated with high rates of macrovascular and microvascular complications. These two pathologies share overlapping risk factors, importantly central obesity. Treatment of hypertension is unequivocally beneficial and improves all-cause mortality, cardiovascular mortality, major cardiovascular events, and microvascular outcomes including nephropathy and retinopathy. Although controversial, current guidelines recommend a target blood pressure in the diabetic population of <140/90 mmHg, which is a similar target to that proposed for individuals without diabetes. Management of blood pressure in patients with diabetes includes both lifestyle modifications and pharmacological therapies. This article reviews the evidence for management of hypertension in patients with type 2 diabetes mellitus, and provides a recommended treatment strategy based on the available data. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

PubMed

Sánchez, Miguel A; Parrott, Wayne A

2017-10-01

GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Individualisation of Lean Concept in Companies Dealing with Mass Production

NASA Astrophysics Data System (ADS)

Bednár, Roman

2012-12-01

The methods of lean manufacturing primarily designed for businesses dealing with serial production, are also used in other types of production. However the concept of lean production was not designed for these types of businesses, they are utilized only partially. Paper focuses on applying methods of lean concept in companies which are dealing with mass production and their options of exchange for other methods in the event of disagreement. Basis of the article is a list of lean methods with its description and its utilization in practice. The questionnaire was utilized to identify information from the practice. Based on this survey were identified the critical methods that are no longer appropriate for companies dealing with mass production. However, there are alternative methods of describing the problem. It is possible to say that companies are trying to get closer to their goal by modification of the basic concepts. And the concept of Lean Enterprise serves as a standard.

Cardiovascular Disease and Primary Ovarian Insufficiency

PubMed Central

Wellons, Melissa

2012-01-01

Cardiovascular disease (CVD) is the number-one killer of women. Women with primary ovarian insufficiency (POI) may be more burdened by cardiovascular disease, such as myocardial infarction and stroke, as compared with women with normal menopause. The increased burden may be mediated by a worsening of cardiovascular risk factors, such as lipids, corresponding with the loss of ovarian function. In contrast, the increased burden may be caused by factors that precede and potentially contribute to both CVD events and ovarian decline, such as X-chromosome abnormalities and smoking. Regardless of the cause, women with POI may serve as an important population to target for CVD screening and prevention strategies. These strategies should include the use of CVD risk stratification tools to identify women that may benefit from lifestyle modification and pharmacological therapy to prevent CVD. Sex steroid therapy for the sole purpose of CVD prevention in women with POI cannot be recommended, based on a lack of evidence. PMID:21969267

Whole genome DNA methylation: beyond genes silencing.

PubMed

Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

2017-01-17

The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the major biological consequences of DNA methylation recently discovered. We also discuss the necessity of tuning DNA methylation resolution into an adequate scale to ease the integration of the methylome information with other chromatin features and transcription events such as gene expression, nucleosome positioning, transcription factors binding dynamic, gene splicing and genomic imprinting. Finally, our review sheds light on DNA methylation heterogeneity in cell population and the different approaches used for its assessment, including the contribution of single cell DNA analysis technology.

Whole genome DNA methylation: beyond genes silencing

PubMed Central

Tirado-Magallanes, Roberto; Rebbani, Khadija; Lim, Ricky; Pradhan, Sriharsa; Benoukraf, Touati

2017-01-01

The combination of DNA bisulfite treatment with high-throughput sequencing technologies has enabled investigation of genome-wide DNA methylation at near base pair level resolution, far beyond that of the kilobase-long canonical CpG islands that initially revealed the biological relevance of this covalent DNA modification. The latest high-resolution studies have revealed a role for very punctual DNA methylation in chromatin plasticity, gene regulation and splicing. Here, we aim to outline the major biological consequences of DNA methylation recently discovered. We also discuss the necessity of tuning DNA methylation resolution into an adequate scale to ease the integration of the methylome information with other chromatin features and transcription events such as gene expression, nucleosome positioning, transcription factors binding dynamic, gene splicing and genomic imprinting. Finally, our review sheds light on DNA methylation heterogeneity in cell population and the different approaches used for its assessment, including the contribution of single cell DNA analysis technology. PMID:27895318

Ball with hair: modular functionalization of highly stable G-quadruplex DNA nano-scaffolds through N2-guanine modification

PubMed Central

Lech, Christopher Jacques

2017-01-01

Abstract Functionalized nanoparticles have seen valuable applications, particularly in the delivery of therapeutic and diagnostic agents in biological systems. However, the manufacturing of such nano-scale systems with the consistency required for biological application can be challenging, as variation in size and shape have large influences in nanoparticle behavior in vivo. We report on the development of a versatile nano-scaffold based on the modular functionalization of a DNA G-quadruplex. DNA sequences are functionalized in a modular fashion using well-established phosphoramidite chemical synthesis with nucleotides containing modification of the amino (N2) position of the guanine base. In physiological conditions, these sequences fold into well-defined G-quadruplex structures. The resulting DNA nano-scaffolds are thermally stable, consistent in size, and functionalized in a manner that allows for control over the density and relative orientation of functional chemistries on the nano-scaffold surface. Various chemistries including small modifications (N2-methyl-guanine), bulky aromatic modifications (N2-benzyl-guanine), and long chain-like modifications (N2-6-amino-hexyl-guanine) are tested and are found to be generally compatible with G-quadruplex formation. Furthermore, these modifications stabilize the G-quadruplex scaffold by 2.0–13.3 °C per modification in the melting temperature, with concurrent modifications producing extremely stable nano-scaffolds. We demonstrate the potential of this approach by functionalizing nano-scaffolds for use within the biotin–avidin conjugation approach. PMID:28499037

Modifications of ORNL's computer programs MSF-21 and VTE-21 for the evaluation and rapid optimization of multistage flash and vertical tube evaporators

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

Glueckstern, P.; Wilson, J.V.; Reed, S.A.

1976-06-01

Design and cost modifications were made to ORNL's Computer Programs MSF-21 and VTE-21 originally developed for the rapid calculation and design optimization of multistage flash (MSF) and multieffect vertical tube evaporator (VTE) desalination plants. The modifications include additional design options to make possible the evaluation of desalting plants based on current technology (the original programs were based on conceptual designs applying advanced and not yet proven technological developments and design features) and new materials and equipment costs updated to mid-1975.

Purity and Cleanness of Aeorgel as a Cosmic Dust Capture Medium

NASA Technical Reports Server (NTRS)

Tsou, P.; Fleming, R.; Lindley, P.; Craig, A.; Blake, D.

1994-01-01

The capability for capturing micrometeoroids intact through laboratory simulations [Tsou 1988] and in space [Tsou 1993] in passive underdense silica aerogel offers a valuable tool for cosmic dust research. The integrity of the sample handling medium can substantially modify the integrity of the sample. Intact capture is a violent hypervelocity event: the integrity of the capturing medium can cause even greater modification of the sample.

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas

PubMed Central

Armero, Victoria E. S.; Tremblay, Marie-Pier; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Duval, Cyntia; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S.

2017-01-01

Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein–Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS. PMID:28493890

Transcriptome-wide analysis of alternative RNA splicing events in Epstein-Barr virus-associated gastric carcinomas.

PubMed

Armero, Victoria E S; Tremblay, Marie-Pier; Allaire, Andréa; Boudreault, Simon; Martenon-Brodeur, Camille; Duval, Cyntia; Durand, Mathieu; Lapointe, Elvy; Thibault, Philippe; Tremblay-Létourneau, Maude; Perreault, Jean-Pierre; Scott, Michelle S; Bisaillon, Martin

2017-01-01

Multiple human diseases including cancer have been associated with a dysregulation in RNA splicing patterns. In the current study, modifications to the global RNA splicing landscape of cellular genes were investigated in the context of Epstein-Barr virus-associated gastric cancer. Global alterations to the RNA splicing landscape of cellular genes was examined in a large-scale screen from 295 primary gastric adenocarcinomas using high-throughput RNA sequencing data. RT-PCR analysis, mass spectrometry, and co-immunoprecipitation studies were also used to experimentally validate and investigate the differential alternative splicing (AS) events that were observed through RNA-seq studies. Our study identifies alterations in the AS patterns of approximately 900 genes such as tumor suppressor genes, transcription factors, splicing factors, and kinases. These findings allowed the identification of unique gene signatures for which AS is misregulated in both Epstein-Barr virus-associated gastric cancer and EBV-negative gastric cancer. Moreover, we show that the expression of Epstein-Barr nuclear antigen 1 (EBNA1) leads to modifications in the AS profile of cellular genes and that the EBNA1 protein interacts with cellular splicing factors. These findings provide insights into the molecular differences between various types of gastric cancer and suggest a role for the EBNA1 protein in the dysregulation of cellular AS.

Multistage Monte Carlo simulation of jet modification in a static medium

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

Cao, S.; Park, C.; Barbieri, R. A.

In this work, the modification of hard jets in an extended static medium held at a fixed temperature is studied using three different Monte Carlo event generators: linear Boltzmann transport (LBT), modular all twist transverse-scattering elastic-drag and radiation (MATTER), and modular algorithm for relativistic treatment of heavy-ion interactions (MARTINI). Each event generator contains a different set of assumptions regarding the energy and virtuality of the partons within a jet versus the energy scale of the medium and, hence, applies to a different epoch in the space-time history of the jet evolution. Here modeling is developed where a jet may sequentiallymore » transition from one generator to the next, on a parton-by-parton level, providing a detailed simulation of the space-time evolution of medium modified jets over a much broader dynamic range than has been attempted previously in a single calculation. Comparisons are carried out for different observables sensitive to jet quenching, including the parton fragmentation function and the azimuthal distribution of jet energy around the jet axis. The effect of varying the boundary between different generators is studied and a theoretically motivated criterion for the location of this boundary is proposed. Lastly, the importance of such an approach with coupled generators to the modeling of jet quenching is discussed.« less

Multistage Monte Carlo simulation of jet modification in a static medium

DOE PAGES

Cao, S.; Park, C.; Barbieri, R. A.; ...

2017-08-22

In this work, the modification of hard jets in an extended static medium held at a fixed temperature is studied using three different Monte Carlo event generators: linear Boltzmann transport (LBT), modular all twist transverse-scattering elastic-drag and radiation (MATTER), and modular algorithm for relativistic treatment of heavy-ion interactions (MARTINI). Each event generator contains a different set of assumptions regarding the energy and virtuality of the partons within a jet versus the energy scale of the medium and, hence, applies to a different epoch in the space-time history of the jet evolution. Here modeling is developed where a jet may sequentiallymore » transition from one generator to the next, on a parton-by-parton level, providing a detailed simulation of the space-time evolution of medium modified jets over a much broader dynamic range than has been attempted previously in a single calculation. Comparisons are carried out for different observables sensitive to jet quenching, including the parton fragmentation function and the azimuthal distribution of jet energy around the jet axis. The effect of varying the boundary between different generators is studied and a theoretically motivated criterion for the location of this boundary is proposed. Lastly, the importance of such an approach with coupled generators to the modeling of jet quenching is discussed.« less

Attributional styles in boys with severe behaviour problems: a possible reason for lack of progress on a positive behaviour programme.

PubMed

Eslea, M

1999-03-01

The number of exclusions from British schools has been increasing in recent years: the vast majority are because of disruptive behaviour. Increasing the effectiveness of behaviour control is therefore a priority for educators. This study tests the hypothesis that children who do not respond well to a behaviour modification regime exhibit a depressed attributional style. The sample comprised 26 boys aged 7-11 in a special day school for children with behaviour problems. Participants were interviewed about positive and negative aspects of school life: responses were coded using the Leeds Attributional Coding System (Stratton et al., 1988). School records were then used to identify children making good progress through the Positive Behaviour Programme (N = 13) and those making little or no progress (N = 8). Mean proportions of stable, global, internal, personal and controllable attributions were compared by progress group (high/low) and outcome (positive/negative) using mixed-design ANOVA. High progress children made significantly more global and internal attributions for positive than for negative events, while low progress children made more personal attributions for negative than for positive events. A depressed attributional style may act as a barrier which hinders the generalisation and internalisation of traditional behaviour modification methods. Increased teacher-awareness of attribution could increase the effectiveness of remedial programmes.

Using a modified time-reverse imaging technique to locate low-frequency earthquakes on the San Andreas Fault near Cholame, California

USGS Publications Warehouse

Horstmann, Tobias; Harrington, Rebecca M.; Cochran, Elizabeth S.

2015-01-01

We present a new method to locate low-frequency earthquakes (LFEs) within tectonic tremor episodes based on time-reverse imaging techniques. The modified time-reverse imaging technique presented here is the first method that locates individual LFEs within tremor episodes within 5 km uncertainty without relying on high-amplitude P-wave arrivals and that produces similar hypocentral locations to methods that locate events by stacking hundreds of LFEs without having to assume event co-location. In contrast to classic time-reverse imaging algorithms, we implement a modification to the method that searches for phase coherence over a short time period rather than identifying the maximum amplitude of a superpositioned wavefield. The method is independent of amplitude and can help constrain event origin time. The method uses individual LFE origin times, but does not rely on a priori information on LFE templates and families.We apply the method to locate 34 individual LFEs within tremor episodes that occur between 2010 and 2011 on the San Andreas Fault, near Cholame, California. Individual LFE location accuracies range from 2.6 to 5 km horizontally and 4.8 km vertically. Other methods that have been able to locate individual LFEs with accuracy of less than 5 km have mainly used large-amplitude events where a P-phase arrival can be identified. The method described here has the potential to locate a larger number of individual low-amplitude events with only the S-phase arrival. Location accuracy is controlled by the velocity model resolution and the wavelength of the dominant energy of the signal. Location results are also dependent on the number of stations used and are negligibly correlated with other factors such as the maximum gap in azimuthal coverage, source–station distance and signal-to-noise ratio.

Direct Detection and Sequencing of Damaged DNA Bases

PubMed Central

2011-01-01

Products of various forms of DNA damage have been implicated in a variety of important biological processes, such as aging, neurodegenerative diseases, and cancer. Therefore, there exists great interest to develop methods for interrogating damaged DNA in the context of sequencing. Here, we demonstrate that single-molecule, real-time (SMRT®) DNA sequencing can directly detect damaged DNA bases in the DNA template - as a by-product of the sequencing method - through an analysis of the DNA polymerase kinetics that are altered by the presence of a modified base. We demonstrate the sequencing of several DNA templates containing products of DNA damage, including 8-oxoguanine, 8-oxoadenine, O6-methylguanine, 1-methyladenine, O4-methylthymine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, or thymine dimers, and show that these base modifications can be readily detected with single-modification resolution and DNA strand specificity. We characterize the distinct kinetic signatures generated by these DNA base modifications. PMID:22185597

Direct detection and sequencing of damaged DNA bases.

PubMed

Clark, Tyson A; Spittle, Kristi E; Turner, Stephen W; Korlach, Jonas

2011-12-20

Products of various forms of DNA damage have been implicated in a variety of important biological processes, such as aging, neurodegenerative diseases, and cancer. Therefore, there exists great interest to develop methods for interrogating damaged DNA in the context of sequencing. Here, we demonstrate that single-molecule, real-time (SMRT®) DNA sequencing can directly detect damaged DNA bases in the DNA template - as a by-product of the sequencing method - through an analysis of the DNA polymerase kinetics that are altered by the presence of a modified base. We demonstrate the sequencing of several DNA templates containing products of DNA damage, including 8-oxoguanine, 8-oxoadenine, O6-methylguanine, 1-methyladenine, O4-methylthymine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, or thymine dimers, and show that these base modifications can be readily detected with single-modification resolution and DNA strand specificity. We characterize the distinct kinetic signatures generated by these DNA base modifications.

Physical, Chemical and Biochemical Modifications of Protein-Based Films and Coatings: An Extensive Review

PubMed Central

Zink, Joël; Wyrobnik, Tom; Prinz, Tobias; Schmid, Markus

2016-01-01

Protein-based films and coatings are an interesting alternative to traditional petroleum-based materials. However, their mechanical and barrier properties need to be enhanced in order to match those of the latter. Physical, chemical, and biochemical methods can be used for this purpose. The aim of this article is to provide an overview of the effects of various treatments on whey, soy, and wheat gluten protein-based films and coatings. These three protein sources have been chosen since they are among the most abundantly used and are well described in the literature. Similar behavior might be expected for other protein sources. Most of the modifications are still not fully understood at a fundamental level, but all the methods discussed change the properties of the proteins and resulting products. Mastering these modifications is an important step towards the industrial implementation of protein-based films. PMID:27563881

Addendum to the Closure Report for Corrective Action Unit 335: Area 6 Injection Well and Drain Pit Nevada Test Site, Nevada, Revison 0

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

Lynn Kidman

This document constitutes an addendum to the June 2003, Closure Report for Corrective Action Unit 335: Area 6 Injection Well and Drain Pit as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consistsmore » of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 06-20-02, 20-inch Cased Hole • CAS 06-23-03, Drain Pit These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the November 2002, Closure Report for Corrective Action Unit 356: Mud Pits and Disposal Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: •more » This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 03-04-01, Area 3 Change House Septic System • CAS 03-09-04, Mud Pit These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 398: Area 25 Spill Sites, Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 2003, Closure Report for Corrective Action Unit 398: Area 25 Spill Sites as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 25-25-17, Subsurface Hydraulic Oil Spill. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 214: Bunkers and Storage Areas Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the September 2006, Closure Report for Corrective Action Unit 214: Bunkers and Storage Areas as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of: • Thismore » cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 25-23-01, Contaminated Materials • CAS 25-23-19, Radioactive Material Storage These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Addendum to the Closure Report for Corrective Action Unit 342: Area 23 Mercury Fire Training Pit Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the April 2000, Closure Report for Corrective Action Unit 342: Area 23 Mercury Fire Training Pit as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, this addendum consists of:more » • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the UR for CAS 23-56-01, Former Mercury Fire Training Pit. This UR was established as part of a Federal Facility Agreement and Consent Order (FFACO) corrective action and is based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since this UR was established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, this UR was re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the UR) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove the UR because contamination is not present at the site above the risk-based FALs. Requirements for inspecting and maintaining this UR will be canceled, and the postings and signage at this site will be removed. Fencing and posting may be present at this site that are unrelated to the FFACO UR such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at this site.« less

Addendum to the Closure Report for Corrective Action Unit 322: Areas 1 & 3 Release Sites and Injection Wells Nevada Test Site, Nevada, Revision 0

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

Lynn Kidman

This document constitutes an addendum to the June 2006, Closure Report for Corrective Action Unit 322: Areas 1 & 3 Release Sites and Injection Wells as described in the document Recommendations and Justifications for Modifications for Use Restrictions Established under the U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office Federal Facility Agreement and Consent Order (UR Modification document) dated February 2008. The UR Modification document was approved by NDEP on February 26, 2008. The approval of the UR Modification document constituted approval of each of the recommended UR modifications. In conformance with the UR Modification document, thismore » addendum consists of: • This cover page that refers the reader to the UR Modification document for additional information • The cover and signature pages of the UR Modification document • The NDEP approval letter • The corresponding section of the UR Modification document This addendum provides the documentation justifying the cancellation of the URs for: • CAS 01-25-01, AST Release • CAS 03-25-03, Mud Plant AST Diesel Release These URs were established as part of Federal Facility Agreement and Consent Order (FFACO) corrective actions and were based on the presence of contaminants at concentrations greater than the action levels established at the time of the initial investigation (FFACO, 1996; as amended August 2006). Since these URs were established, practices and procedures relating to the implementation of risk-based corrective actions (RBCA) have changed. Therefore, these URs were re-evaluated against the current RBCA criteria as defined in the Industrial Sites Project Establishment of Final Action Levels (NNSA/NSO, 2006c). This re-evaluation consisted of comparing the original data (used to define the need for the URs) to risk-based final action levels (FALs) developed using the current Industrial Sites RBCA process. The re-evaluation resulted in a recommendation to remove these URs because contamination is not present at these sites above the risk-based FALs. Requirements for inspecting and maintaining these URs will be canceled, and the postings and signage at each site will be removed. Fencing and posting may be present at these sites that are unrelated to the FFACO URs such as for radiological control purposes as required by the NV/YMP Radiological Control Manual (NNSA/NSO, 2004f). This modification will not affect or modify any non-FFACO requirements for fencing, posting, or monitoring at these sites.« less

Optimal Control Modification for Robust Adaptation of Singularly Perturbed Systems with Slow Actuators

NASA Technical Reports Server (NTRS)

Nguyen, Nhan T.; Ishihara, Abraham; Stepanyan, Vahram; Boskovic, Jovan

2009-01-01

Recently a new optimal control modification has been introduced that can achieve robust adaptation with a large adaptive gain without incurring high-frequency oscillations as with the standard model-reference adaptive control. This modification is based on an optimal control formulation to minimize the L2 norm of the tracking error. The optimal control modification adaptive law results in a stable adaptation in the presence of a large adaptive gain. This study examines the optimal control modification adaptive law in the context of a system with a time scale separation resulting from a fast plant with a slow actuator. A singular perturbation analysis is performed to derive a modification to the adaptive law by transforming the original system into a reduced-order system in slow time. The model matching conditions in the transformed time coordinate results in increase in the feedback gain and modification of the adaptive law.

Impact of acid and oxidative modifications, single or dual, of sorghum starch on biodegradable films.

PubMed

Biduski, Bárbara; Silva, Francine Tavares da; Silva, Wyller Max da; Halal, Shanise Lisie de Mello El; Pinto, Vania Zanella; Dias, Alvaro Renato Guerra; Zavareze, Elessandra da Rosa

2017-01-01

The objective of this study was to evaluate the effects of acid and oxidation modifications on sorghum starch, as well as the effect of dual modification of starch on the physical, morphological, mechanical, and barrier properties of biodegradable films. The acid modification was performed with 3% lactic acid and the oxidation was performed with 1.5% active chlorine. For dual modification, the acid modification was performed first, followed by oxidation under the same conditions as above. Both films of the oxidized starches, single and dual, had increased stiffness, providing a higher tensile strength and lower elongation when compared to films based on native and single acid modified starches. However, the dual modification increased the water vapor permeability of the films without changing their solubility. The increase in sorghum starch concentration in the filmogenic solution increased the thickness, water vapor permeability, and elongation of the films. Copyright © 2016. Published by Elsevier Ltd.

Modification of Sr on 4004 Aluminum Alloy

NASA Astrophysics Data System (ADS)

Guo, Erjun; Cao, Guojian; Feng, Yicheng; Wang, Liping; Wang, Guojun; Lv, Xinyu

2013-05-01

As a brazing foil, 4004 Al alloy has good welding performance. However, the high Si content decreases the plasticity of the alloy. To improve the plasticity of 4004 Al alloy and subsequently improve the productivity of 4004 Al foil or 434 composite foil, 4004 Al alloy was modified by Al-10%Sr master alloy. Modification effects of an additional amount of Sr, modification temperature, and holding time on 4004 aluminum alloy were studied by orthogonal design. The results showed that the greatest impact parameter of 4004 aluminum alloy modification was the additional amount of Sr, followed by holding time and modification temperature. The optimum modification parameters obtained by orthogonal design were as follows: Sr addition of 0.04%, holding time of 60 min, and modification temperature of 760°C. The effect of Sr addition on modification was analyzed in detail based on orthogonal results. With increasing of Sr addition, elongation of 4004 alloy increased at first, and decreased after reaching the maximum value.

Chemical methods for encoding and decoding of posttranslational modifications

PubMed Central

Chuh, Kelly N.; Batt, Anna R.; Pratt, Matthew R.

2016-01-01

A large array of posttranslational modifications can dramatically change the properties of proteins and influence different aspects of their biological function such as enzymatic activity, binding interactions, and proteostasis. Despite the significant knowledge that has been gained about the function of posttranslational modifications using traditional biological techniques, the analysis of the site-specific effects of a particular modification, the identification of the full compliment of modified proteins in the proteome, and the detection of new types of modifications remains challenging. Over the years, chemical methods have contributed significantly in both of these areas of research. This review highlights several posttranslational modifications where chemistry-based approaches have made significant contributions to our ability to both prepare homogeneously modified proteins and identify and characterize particular modifications in complex biological settings. As the number and chemical diversity of documented posttranslational modifications continues to rise, we believe that chemical strategies will be essential to advance the field in years to come. PMID:26933738

Impact of Sofosbuvir-Based Regimens for the Treatment of Hepatitis C After Liver Transplant on Renal Function: Results of a Canadian National Retrospective Study.

PubMed

Faisal, Nabiha; Bilodeau, Marc; Aljudaibi, Bandar; Hirch, Geri; Yoshida, Eric M; Hussaini, Trana; Ghali, Maged P; Congly, Stephen E; Ma, Mang M; Lilly, Leslie B

2018-04-04

We assessed the impact of sofosbuvir-based regimens on renal function in liver transplant recipients with recurrent hepatitis C virus and the role of renal function on the efficacy and safety of these regimens. In an expanded pan-Canadian cohort, 180 liver transplant recipients were treated with sofosbuvir-based regimens for hepatitis C virus recurrence from January 2014 to May 2015. Mean age was 58 ± 6.85 years, and 50% had F3/4 fibrosis. Patients were stratified into 4 groups based on baseline estimated glomerular filtration rate (calculated by the Modification of Diet in Renal Disease formula): < 30, 30 to 45, 46 to 60, and > 60 mL/min/173 m2. The primary outcome was posttreatment changes in renal function from baseline. Secondary outcomes included sustained virologic response at 12 weeks posttreatment and anemia-related and serious adverse events. Posttreatment renal function was improved in most patients (58%). Renal function declined in 22% of patients, which was more marked in those with estimated glomerular filtration rate < 30 mL/min/173 m2, advanced cirrhosis (P = .05), and aggressive hepatitis C virus/fibrosing cholestatic hepatitis (P < .05). High rates (80%-88%) of sustained virologic response at 12 weeks posttreatment were seen across all renal function strata. Cirrhotic patients with glomerular filtration rates < 30 mL/min/173 m2 had sustained virologic response rates at 12 weeks posttreatment comparable to the overall patient group. Rates of anemia-related adverse events and transfusion requirements increased across decreasing estimated glomerular filtration rate groups, with notably more occurrences with ribavirin-based regimens. Sofosbuvir-based regimens improved overall renal function in liver transplant recipients, with sustained virologic response, suggesting an association of subclinical hepatitis C virus-related renal disease. Sustained virologic response rates at 12 weeks posttreatment (80%-88%) were comparable regardless of baseline renal function but lower in cirrhosis.

Polysomnographic Findings in a Cohort of Chronic Insomnia Patients with Benzodiazepine Abuse

PubMed Central

Mazza, Marianna; Losurdo, Anna; Testani, Elisa; Marano, Giuseppe; Di Nicola, Marco; Dittoni, Serena; Gnoni, Valentina; Di Blasi, Chiara; Giannantoni, Nadia Mariagrazia; Lapenta, Leonardo; Brunetti, Valerio; Bria, Pietro; Janiri, Luigi; Mazza, Salvatore; Della Marca, Giacomo

2014-01-01

Study Objectives: To evaluate sleep modifications induced by chronic benzodiazepine (BDZ) abuse. Methods: Cohort study, comparison of sleep measures between BDZs abusers and controls. Drug Addiction Unit (Institute of Psychiatry) and Unit of Sleep Disorders (Institute of Neurology) of the Catholic University in Rome. Six outpatients affected by chronic BDZ abuse were enrolled, (4 men, 2 women, mean age 53.3 ± 14.8, range: 34-70 years); 55 healthy controls were also enrolled (23 men, 32 women, mean age 54.2 ± 13.0, range: 27-76 years). All patients underwent clinical evaluation, psychometric measures, ambulatory polysomnography, scoring of sleep macrostructure and microstructure (power spectral fast-frequency EEG arousal, cyclic alternating pattern [CAP]), and heart rate variability. Results: BDZ abusers had relevant modification of sleep macrostructure and a marked reduction of fast-frequency EEG arousal in NREM (patients: 6.6 ± 3.7 events/h, controls 13.7 ± 4.9 events/h, U-test: 294, p = 0.002) and REM (patients: 8.4 ± 2.4 events/h, controls 13.3 ± 5.1 events/h, U-test: 264, p = 0.016), and of CAP rate (patients: 15.0 ± 8.6%, controls: 51.2% ± 12.1%, U-test: 325, p < 0.001). Discussion: BDZ abusers have reduction of arousals associated with increased number of nocturnal awakenings and severe impairment of sleep architecture. The effect of chronic BDZ abuse on sleep may be described as a severe impairment of arousal dynamics; the result is the inability to modulate levels of vigilance. Citation: Mazza M; Losurdo A; Testani E; Marano G; Di Nicola M; Dittoni S; Gnoni V; Di Blasi C; Giannantoni NM; Lapenta L; Brunetti V; Bria P; Janiri L; Mazza S; Della Marca G. Polysomnographic findings in a cohort of chronic insomnia patients with benzodiazepine abuse. J Clin Sleep Med 2014;10(1):35-42. PMID:24426818

Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes.

PubMed

Chow, Clara K; Jolly, Sanjit; Rao-Melacini, Purnima; Fox, Keith A A; Anand, Sonia S; Yusuf, Salim

2010-02-16

Although preventive drug therapy is a priority after acute coronary syndrome, less is known about adherence to behavioral recommendations. The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events. The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS) 5 randomized clinical trial. At the 30-day follow-up, patients reported adherence to diet, physical activity, and smoking cessation. Cardiovascular events (myocardial infarction, stroke, cardiovascular death) and all-cause mortality were documented to 6 months. About one third of smokers persisted in smoking. Adherence to neither diet nor exercise recommendations was reported by 28.5%, adherence to either diet or exercise by 41.6%, and adherence to both by 29.9%. In contrast, 96.1% of subjects reported antiplatelet use, 78.9% reported statin use, and 72.4% reported angiotensin-converting enzyme/angiotensin receptor blocker use. Quitting smoking was associated with a decreased risk of myocardial infarction compared with persistent smoking (odds ratio, 0.57; 95% confidence interval, 0.36 to 0.89). Diet and exercise adherence was associated with a decreased risk of myocardial infarction compared with nonadherence (odds ratio, 0.52; 95% confidence interval, 0.4 to 0.69). Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold (95% confidence interval, 2.5 to 5.9) increased risk of myocardial infarction/stroke/death compared with never smokers who modified diet and exercise. Adherence to behavioral advice (diet, exercise, and smoking cessation) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events. These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome. Clinical Trial Registration Information- URL: http://clinicaltrials.gov/ct2/show/NCT00139815. Unique identifier: NCT00139815.

Impact of climate change on runoff pollution in urban environments

NASA Astrophysics Data System (ADS)

Coutu, S.; Kramer, S.; Barry, D. A.; Roudier, P.

2012-12-01

Runoff from urban environments is generally contaminated. These contaminants mostly originate from road traffic and building envelopes. Facade envelopes generate lead, zinc and even biocides, which are used for facade protection. Road traffic produces particles from tires and brakes. The transport of these pollutants to the environment is controlled by rainfall. The interval, duration and intensity of rainfall events are important as the dynamics of the pollutants are often modeled with non-linear buildup/washoff functions. Buildup occurs during dry weather when pollution accumulates, and is subsequently washed-off at the time of the following rainfall, contaminating surface runoff. Climate predictions include modified rainfall distributions, with changes in both number and intensity of events, even if the expected annual rainfall varies little. Consequently, pollutant concentrations in urban runoff driven by buildup/washoff processes will be affected by these changes in rainfall distributions. We investigated to what extent modifications in future rainfall distributions will impact the concentrations of pollutants present in urban surface runoff. The study used the example of Lausanne, Switzerland (temperate climate zone). Three emission scenarios (time horizon 2090), multiple combinations of RCM/GCM and modifications in rain event frequency were used to simulate future rainfall distributions with various characteristics. Simulated rainfall events were used as inputs for four pairs of buildup/washoff models, in order to compare future pollution concentrations in surface runoff. In this way, uncertainty in model structure was also investigated. Future concentrations were estimated to be between ±40% of today's concentrations depending on the season and, importantly, on the choice of the RCM/GCM model. Overall, however, the dominant factor was the uncertainty inherent in buildup/washoff models, which dominated over the uncertainty in future rainfall distributions. Consequently, the choice of a proper buildup/washoff model, with calibrated site-specific coefficients, is a major factor in modeling future runoff concentrations from contaminated urban surfaces.

Histones and their modifications in ovarian cancer - drivers of disease and therapeutic targets.

PubMed

Marsh, Deborah J; Shah, Jaynish S; Cole, Alexander J

2014-01-01

Epithelial ovarian cancer has the highest mortality of the gynecological malignancies. High grade serous epithelial ovarian cancer (SEOC) is the most common subtype, with the majority of women presenting with advanced disease where 5-year survival is around 25%. Platinum-based chemotherapy in combination with paclitaxel remains the most effective treatment despite platinum therapies being introduced almost 40 years ago. Advances in molecular medicine are underpinning new strategies for the treatment of cancer. Major advances have been made by international initiatives to sequence cancer genomes. For SEOC, with the exception of TP53 that is mutated in virtually 100% of these tumors, there is no other gene mutated at high frequency. There is extensive copy number variation, as well as changes in methylation patterns that will influence gene expression. To date, the role of histones and their post-translational modifications in ovarian cancer is a relatively understudied field. Post-translational histone modifications play major roles in gene expression as they direct the configuration of chromatin and so access by transcription factors. Histone modifications include methylation, acetylation, and monoubiquitination, with involvement of enzymes including histone methyltransferases, histone acetyltransferases/deacetylases, and ubiquitin ligases/deubiquitinases, respectively. Complexes such as the Polycomb repressive complex also play roles in the control of histone modifications and more recently roles for long non-coding RNA and microRNAs are emerging. Epigenomic-based therapies targeting histone modifications are being developed and offer new approaches for the treatment of ovarian cancer. Here, we discuss histone modifications and their aberrant regulation in malignancy and specifically in ovarian cancer. We review current and upcoming histone-based therapies that have the potential to inform and improve treatment strategies for women with ovarian cancer.

The clinical database and implementation of treatment guidelines by the Danish Breast Cancer Cooperative Group in 2007-2016.

PubMed

Jensen, Maj-Britt; Laenkholm, Anne-Vibeke; Offersen, Birgitte V; Christiansen, Peer; Kroman, Niels; Mouridsen, Henning T; Ejlertsen, Bent

2018-01-01

Since 40 years, Danish Breast Cancer Cooperative Group (DBCG) has provided comprehensive guidelines for diagnosis and treatment of breast cancer. This population-based analysis aimed to describe the plurality of modifications introduced over the past 10 years in the national Danish guidelines for the management of early breast cancer. By use of the clinical DBCG database we analyze the effectiveness of the implementation of guideline revisions in Denmark. From the DBCG guidelines we extracted modifications introduced in 2007-2016 and selected examples regarding surgery, radiotherapy (RT) and systemic treatment. We assessed introduction of modifications from release on the DBCG webpage to change in clinical practice using the DBCG clinical database. Over a 10-year period data from 48,772 patients newly diagnosed with malignant breast tumors were entered into DBCG's clinical database and 42,197 of these patients were diagnosed with an invasive carcinoma following breast conserving surgery (BCS) or mastectomy. More than twenty modifications were introduced in the guidelines. Implementations, based on prospectively collected data, varied widely; exemplified with around one quarter of the patients not treated according to a specific guideline within one year from the introduction, to an almost immediate full implantation. Modifications of the DBCG guidelines were generally well implemented, but the time to full implementation varied from less than one year up to around five years. Our data is registry based and does not allow a closer analysis of the causes for delay in implementation of guideline modifications.

What’s bad in cancer is good in the embryo: Importance of EMT in neural crest development

PubMed Central

Kerosuo, Laura; Bronner-Fraser, Marianne

2012-01-01

Although the epithelial to mesenchymal transition (EMT) is famous for its role in cancer metastasis, it also is a normal developmental event in which epithelial cells are converted into migratory mesenchymal cells. A prime example of EMT during development occurs when neural crest (NC) cells emigrate from the neural tube thus providing an excellent model to study the principles of EMT in a nonmalignant environment. NC cells start life as neuroepithelial cells intermixed with precursors of the central nervous system. After EMT, they delaminate and begin migrating, often to distant sites in the embryo. While proliferating and maintaining multipotency and cell survival the transitioning neural crest cells lose apicobasal polarity and the basement membrane is broken down. This review discusses how these events are coordinated and regulated, by series of events involving signaling factors, gene regulatory interactions, as well as epigenetic and post-transcriptional modifications. Even though the series of events involved in NC EMT are well known, the sequence in which these steps take place remains a subject of debate, raising the intriguing possibility that, rather than being a single event, neural crest EMT may involve multiple parallel mechanisms. PMID:22430756

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

Baumgardt, D.R.; Carter, S.; Maxson, M.

The objective of this project is to design and develop an Intelligent Event Identification System, or ISEIS, which will be a prototype for routine event identification of small explosions and earthquakes and to serve as a tool for discrimination research. The first part of this study gives an overview of the system design and the results of a preliminary evaluation of the system on events in Scandinavia and the Soviet Union. The system was designed to be highly modular to allow the easy incorporation of new discriminants and/or discrimination processes. Because the main objective of the system is the identificationmore » of small events, most of the initial ISEIS prototype discriminants utilize regional seismic data recorded by the regional arrays, NORESS and ARCESS. However, ISEIS can easily process other regional array data (e.g., from GERESS and FINESA), as well as data from three-component single stations, as more of this data becomes available. The second part of this study is entitled Intelligent Event Identification System: User's Manual, and gives a detailed description of all the processing interfaces of ISEIS. The third part of this study is entitled Intelligent Event Identification System: Software Maintenance Manual, which describes the ISEIS software from the programmer's perspective and provides information for maintenance and modification of the software modules in the system.« less

Germination and Outgrowth of Single Spores of Saccharomyces cerevisiae Viewed by Scanning Electron and Phase-Contrast Microscopy

PubMed Central

Rousseau, Paul; Halvorson, Harlyn O.; Bulla, Lee A.; Julian, Grant St.

1972-01-01

Single spores of Saccharomyces cerevisiae were examined during germination and outgrowth by scanning electron and phase-contrast microscopy. Also determined were changes in cell weight and light absorbance, trehalose utilization, and synthesis of protein and KOH-soluble carbohydrates. These studies reveal that development of the vegetative cell from a spore follows a definite sequence of events involving dramatic physical and chemical modifications. These changes are: initial rapid loss in cellular absorbance followed later by an abrupt gain in absorbance; reduction in cell weight and a subsequent progressive increase; modification of the spore surface with concomitant diminution in refractility; elongation of the cell and augmentation of surface irregularities; rapid decline in trehalose content of the cell accompanied by extensive formation of KOH-soluble carbohydrates; and bud formation. Images PMID:4551750

Nanoscale surface modifications of medically relevant metals: state-of-the art and perspectives.

PubMed

Variola, Fabio; Brunski, John B; Orsini, Giovanna; Tambasco de Oliveira, Paulo; Wazen, Rima; Nanci, Antonio

2011-02-01

Evidence that nanoscale surface properties stimulate and guide various molecular and biological processes at the implant/tissue interface is fostering a new trend in designing implantable metals. Cutting-edge expertise and techniques drawn from widely separated fields, such as nanotechnology, materials engineering and biology, have been advantageously exploited to nanoengineer surfaces in ways that control and direct these processes in predictable manners. In this review, we present and discuss the state-of-the-art of nanotechnology-based approaches currently adopted to modify the surface of metals used for orthopedic and dental applications, and also briefly consider their use in the cardiovascular field. The effects of nanoengineered surfaces on various in vitro molecular and cellular events are firstly discussed. This review also provides an overview of in vivo and clinical studies with nanostructured metallic implants, and addresses the potential influence of nanotopography on biomechanical events at interfaces. Ultimately, the objective of this work is to give the readership a comprehensive picture of the current advances, future developments and challenges in the application of the infinitesimally small to biomedical surface science. We believe that an integrated understanding of the in vitro and particularly of the in vivo behavior is mandatory for the proper exploitation of nanostructured implantable metals and, indeed, of all biomaterials.

Surfacers change their dive tactics depending on the aim of the dive: evidence from simultaneous measurements of breaths and energy expenditure.

PubMed

Okuyama, Junichi; Tabata, Runa; Nakajima, Kana; Arai, Nobuaki; Kobayashi, Masato; Kagawa, Shiro

2014-11-22

Air-breathing divers are assumed to have evolved to apportion their time between surface and underwater periods to maximize the benefit gained from diving activities. However, whether they change their time allocation depending on the aim of the dive is still unknown. This may be particularly crucial for 'surfacers' because they dive for various purposes in addition to foraging. In this study, we counted breath events at the surface and estimated oxygen consumption during resting, foraging and other dives in 11 green turtles (Chelonia mydas) in the wild. Breath events were counted by a head-mounted acceleration logger or direct observation based on an animal-borne video logger, and oxygen consumption was estimated by measuring overall dynamic body acceleration. Our results indicate that green turtles maximized their submerged time, following this with five to seven breaths to replenish oxygen for resting dives. However, they changed their dive tactic during foraging and other dives; they surfaced without depleting their estimated stores of oxygen, followed by only a few breaths for effective foraging and locomotion. These dichotomous surfacing tactics would be the result of behavioural modifications by turtles depending on the aim of each dive. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Mindfulness training for adolescents: A neurodevelopmental perspective on investigating modifications in attention and emotion regulation using event-related brain potentials.

PubMed

Sanger, Kevanne Louise; Dorjee, Dusana

2015-09-01

Mindfulness training is increasingly being introduced in schools, yet studies examining its impact on the developing brain have been scarce. A neurodevelopmental perspective on mindfulness has been advocated as a powerful tool to enhance our understanding of underlying neurocognitive changes that have implications for developmental well-being research and the implementation of mindfulness in education. To stimulate more research in the developmental cognitive neuroscience of mindfulness, this article outlines possible indexes of mindfulness-based change in adolescence, with a focus on event-related brain potential (ERP) markers. We provide methodological recommendations for future studies and offer examples of research paradigms. We also discuss how mindfulness practice could impact on the development of prefrontal brain structures and enhance attention control and emotion regulation skills in adolescents, impacting in turn on their self-regulation and coping skills. We highlight advantages of the ERP methodology in neurodevelopmental research of mindfulness. It is proposed that research using established experimental tasks targeting ERP components such as the contingent negative variability, N200, error-related negativity and error positivity, P300, and late positive potential could elucidate developmentally salient shifts in the neural plasticity of the adolescent brain induced by mindfulness practice.

Investigating the correlation of the U.S. Air Force Physical Fitness Test to combat-based fitness: a women-only study.

PubMed

Mitchell, Tarah; White, Edward D; Ritschel, Daniel

2014-06-01

The primary objective in this research involves determining the Air Force Physical Fitness Test's (AFPFT) predictability of combat fitness and whether measures within the AFPFT require modification to increase this predictability further. We recruited 60 female volunteers and compared their performance on the AFPFT to the Marine Combat Fitness Test, the proxy for combat fitness. We discovered little association between the two (R(2) of 0.35), however, this association significantly increased (adjusted R(2) of 0.56) when utilizing the raw scores of the AFPFT instead of using the gender/age scoring tables. Improving on these associations, we develop and propose a simple ordinary least squares regression model that minimally impacts the AFPFT testing routine. This two-event model for predicting combat fitness incorporates the 1.5-mile run along with the number of repetitions of a 30-lb dumbbell from chest height to overhead with arms extended during a 2-minute time span. These two events predicted combat fitness as assessed by the Marine Combat Fitness Test with an adjusted R(2) of 0.82. By adopting this model, we greatly improve the Air Force's ability to assess combat fitness for women. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Surfacers change their dive tactics depending on the aim of the dive: evidence from simultaneous measurements of breaths and energy expenditure

PubMed Central

Okuyama, Junichi; Tabata, Runa; Nakajima, Kana; Arai, Nobuaki; Kobayashi, Masato; Kagawa, Shiro

2014-01-01

Air-breathing divers are assumed to have evolved to apportion their time between surface and underwater periods to maximize the benefit gained from diving activities. However, whether they change their time allocation depending on the aim of the dive is still unknown. This may be particularly crucial for ‘surfacers’ because they dive for various purposes in addition to foraging. In this study, we counted breath events at the surface and estimated oxygen consumption during resting, foraging and other dives in 11 green turtles (Chelonia mydas) in the wild. Breath events were counted by a head-mounted acceleration logger or direct observation based on an animal-borne video logger, and oxygen consumption was estimated by measuring overall dynamic body acceleration. Our results indicate that green turtles maximized their submerged time, following this with five to seven breaths to replenish oxygen for resting dives. However, they changed their dive tactic during foraging and other dives; they surfaced without depleting their estimated stores of oxygen, followed by only a few breaths for effective foraging and locomotion. These dichotomous surfacing tactics would be the result of behavioural modifications by turtles depending on the aim of each dive. PMID:25297856

Infrasound pulses from lightning and electrostatic field changes: Observation and discussion

NASA Astrophysics Data System (ADS)

Chum, J.; Diendorfer, G.; Å indelářová, T.; Baše, J.; Hruška, F.

2013-10-01

Narrow (~1-2 s) infrasound pulses that followed, with ~11 to ~50 s delays, rapid changes of electrostatic field were observed by a microbarometer array in the Czech Republic during thunderstorm activity. A positive pressure fluctuation (compression phase) always preceded decompression; the compression was usually higher than the decompression. The angles of arrival (azimuth and elevation) were analyzed for selected distinct events. Comparisons of distances and azimuths of infrasound sources from the center of microbarometer array with lightning locations determined by the European Cooperation for Lighting Detection lightning detection network show that most of the selected events can be very likely associated with intracloud (IC) discharges. The preceding rapid changes of electrostatic field, their potential association with IC discharges, and high-elevation angles of arrival for near infrasound sources indicate that an electrostatic mechanism is probably responsible for their generation. It is discussed that distinguishing the relative role of thermal and electrostatic mechanism is difficult and that none of the published models of electrostatic production of infrasound thunder can explain the presented observations precisely. A modification of the current models, based on consideration of at least two charged layers, is suggested. Further theoretical and experimental investigations are however needed to get a better description of the generation mechanism.

[Variations in the epidemiolgy of adverse events: methodology of the Harvard Medical Practice Design].

PubMed

Lessing, C; Schmitz, A; Schrappe, M

2012-02-01

The Harvard Medical Practice (HMP) Design is based on a multi-staged retrospective review of inpatient records and is used to assess the frequency of (preventable) adverse events ([P]AE) in large study populations. Up to now HMP studies have been conducted in 9 countries. Results differ largely from 2.9% to 3.7% of patients with AE in the USA up to 16.6% in Australia. In our analysis we systematically compare the methodology of 9 HMP studies published in the English language and discuss possible impacts on reported frequencies. Modifications in HMP studies can be individualised from each stage of planning, conducting, and reporting results. In doing so 2 studies from the USA with lowest rates of AE can be characterised by their context of liability and the absence of screening for nosocomial infections. Studies with a high proportion of AE are marked by an intense training of reviewers. Further conclusions are hindered by divergences in defining periods of observation, by presenting frequencies as cumulative prevalences, and differences in the reporting of study results. As a consequence future HMP studies should go for complete, consistent and transparent coverage. Further research should concentrate on advancing methods for collecting data on (P)AE. © Georg Thieme Verlag KG Stuttgart · New York.

Nanoscale surface modifications of medically-relevant metals: state-of-the art and perspectives

PubMed Central

Variola, Fabio; Brunski, John; Orsini, Giovanna; de Oliveira, Paulo Tambasco; Wazen, Rima; Nanci, Antonio

2011-01-01

Evidence that nanoscale surface properties stimulate and guide various molecular and biological processes at the implant/tissue interface is fostering a new trend in designing implantable metals. Cutting-edge expertise and techniques drawn from widely separated fields, such as nanotechnology, materials engineering and biology, have been advantageously exploited to nanoengineer surfaces in ways that control and direct these processes in predictable manners. In this review, we present and discuss the state-of-the-art of nanotechnology-based approaches currently used to modify the surface of metals used for orthopedic and dental applications, and also briefly consider their use in the cardiovascular field. The effects of nanoengineered surfaces on various in vitro molecular and cellular events are firstly discussed. Importantly, this review also provides an overview of in vivo and clinical studies with nanostructured metallic implants, and addresses the potential influence of nanotopography on biomechanical events at interfaces. Ultimately the objective of this work is to give the readership a comprehensive picture of the current advances, future developments and challenges in the application of the infinitesimally small to biomedical surface science. We believe that an integrated understanding of the in vitro and particularly of the in vivo behavior is mandatory for the proper exploitation of nanostructured implantable metals and, as a matter of fact, all biomaterials. PMID:20976359

Attractor Structures of Signaling Networks: Consequences of Different Conformational Barcode Dynamics and Their Relations to Network-Based Drug Design.

PubMed

Szalay, Kristóf Z; Nussinov, Ruth; Csermely, Peter

2014-06-01

Conformational barcodes tag functional sites of proteins and are decoded by interacting molecules transmitting the incoming signal. Conformational barcodes are modified by all co-occurring allosteric events induced by post-translational modifications, pathogen, drug binding, etc. We argue that fuzziness (plasticity) of conformational barcodes may be increased by disordered protein structures, by integrative plasticity of multi-phosphorylation events, by increased intracellular water content (decreased molecular crowding) and by increased action of molecular chaperones. This leads to increased plasticity of signaling and cellular networks. Increased plasticity is both substantiated by and inducing an increased noise level. Using the versatile network dynamics tool, Turbine (www.turbine.linkgroup.hu), here we show that the 10 % noise level expected in cellular systems shifts a cancer-related signaling network of human cells from its proliferative attractors to its largest, apoptotic attractor representing their health-preserving response in the carcinogen containing and tumor suppressor deficient environment modeled in our study. Thus, fuzzy conformational barcodes may not only make the cellular system more plastic, and therefore more adaptable, but may also stabilize the complex system allowing better access to its largest attractor. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Full-Wave Radio Characterization of Ionospheric Modification at HAARP

DTIC Science & Technology

2015-07-26

Full-Wave Radio Characterization of Ionospheric Modification at HAARP We have studied electrostatic and electromagnetic turbulence stimulated by...radio receivers at HAARP in Alaska, and ground-based radio receivers, incoherent scatter radars, and in-situ measurements from Canadian, ESA, and Polish...363255 San Juan, PR 00936 -3255 31-May-2015 ABSTRACT Final Report: Full-Wave Radio Characterization of Ionospheric Modification at HAARP Report Title We

Effect of Pre-Ozonation and UF Membrane Modification with CNT on Fouling Control

NASA Astrophysics Data System (ADS)

Wang, Kailun; Guan, Yuqi; Zhu, Xuedong; Dong, Dan; Guo, Jin

2018-01-01

The effect of carbon nanotubes (CNT) modification on ultrafiltration membrane fouling control was explored. Three kinds of base membrane were chosen in the study: 20 kDa polysulfone (PS) membrane, 20 kDa and 100 kDa polyethersulfone (PES) membrane. Besides, the effect of pre-ozonation on the three CNT modified membranes for fouling alleviation was further studied. CNT modification presented antifouling properties at the beginning of filtration, while the recoverability of the CNT modified membranes are relatively lower as for the blocking of CNT layer by foulants. Pre-ozonation with a lower ozone concentration (0.25 mgO3/mgDOC) did not efficiently alleviate the fouling of CNT modified membranes. With the ozone concentration increased to 0.81 mgO3/mgDOC, the CNT modified membranes exhibited their higher antifouling properties. Water quality analysis results showed that CNT modification presented a higher capture ability for the humic-like and protein-like substances. After pre-ozonation, more organic materials could be retained in the interior of CNT layer, which decreased the fouling of base membranes and increased the permeate quality as well. Base membrane with large molecular size cut-off is more helpful for the synergistic effect of pre-ozonation and CNT modification.

Stressful life events and depressive problems in early adolescent boys and girls: the influence of parental depression, temperament and family environment.

PubMed

Bouma, Esther M C; Ormel, Johan; Verhulst, Frank C; Oldehinkel, Albertine J

2008-01-01

Stressful life events increase the probability of depressive problems in early adolescence. Several genetic and environmental risk factors may change individual sensitivity to the depressogenic effect of these events. We examined modification by parental depression and gender, and mediation of the former by temperament and family environment. Data were collected as part of a longitudinal cohort study of (pre)adolescents (n = 2127). During the first assessment wave at approximately age 11, we assessed parental depression, family functioning, perceived parenting behaviours, and temperamental frustration and fearfulness. At the second wave, about two and a half years later, stressful life events between the first and second assessment were assessed. Depressive problems were measured at both waves. Adolescents with parents who had a (lifetime) depressive episode were more sensitive to the depressogenic effect of stressful events than adolescents without depressed parents. Furthermore, girls are more sensitive to these effects than boys. The modifying effect of parental depression was not mediated by temperament, family functioning and perceived parenting. Life events were assessed without consideration of contextual information. Depressive problems were measured by questionnaires that did not directly represent DSM-IV criteria. The measure of parental depression was unspecific regarding severity and timing of depressive episodes. The results suggest that gender and parental depression are associated with increased sensitivity to depression after experiencing stressful life events during adolescence.

Mutagenic Spectra Arising from Replication Bypass of the 2,6-diamino-4-hydroxy-N5-methyl Formamidopyrimidine Adduct in Primate Cells

PubMed Central

Earley, Lauriel F.; Minko, Irina G.; Christov, Plamen P.; Rizzo, Carmelo J.; Lloyd, R. Stephen

2013-01-01

DNA exposures to electrophilic methylating agents that are commonly used during chemotherapeutic treatments cause diverse chemical modifications of nucleobases, with reaction at N7-dG being the most abundant. Although this base modification frequently results in destabilization of the glycosyl bond and spontaneous depurination, the adduct can react with hydroxide ion to yield a stable, ring-opened MeFapy-dG and this lesion has been reported to persist in animal tissues. Results from prior in vitro replication bypass investigations of the MeFapy-dG adduct had revealed complex spectra of replication errors that differed depending on the identity of DNA polymerase and the local sequence context. In this study, a series of nine site-specifically modified MeFapy-dG-containing oligodeoxynucleotides were engineered into a shuttle vector and subjected to replication in primate cells. In all nine sequence contexts examined, MeFapy-dG was shown to be associated with a strong mutator phenotype, predominantly causing base substitutions, with G to T transversions being most common. Single and dinucleotide deletions were also found in a subset of the sequence contexts. Interestingly, single-nucleotide deletions occurred not only at the adducted site, but also one nucleotide downstream of the adduct. Standard models for primer-template misalignment could account for some, but not all mutations observed. These data demonstrate that in addition to mutagenesis predicted from replication of DNAs containing O6-Me-dG and O4-Me-dT, the MeFapy-dG adduct likely contributes to mutagenic events following chemotherapeutic treatments. PMID:23763662

The electronics system for the LBNL positron emission mammography (PEM) camera

NASA Astrophysics Data System (ADS)

Moses, W. W.; Young, J. W.; Baker, K.; Jones, W.; Lenox, M.; Ho, M. H.; Weng, M.

2001-06-01

Describes the electronics for a high-performance positron emission mammography (PEM) camera. It is based on the electronics for a human brain positron emission tomography (PET) camera (the Siemens/CTI HRRT), modified to use a detector module that incorporates a photodiode (PD) array. An application-specified integrated circuit (ASIC) services the photodetector (PD) array, amplifying its signal and identifying the crystal of interaction. Another ASIC services the photomultiplier tube (PMT), measuring its output and providing a timing signal. Field-programmable gate arrays (FPGAs) and lookup RAMs are used to apply crystal-by-crystal correction factors and measure the energy deposit and the interaction depth (based on the PD/PMT ratio). Additional FPGAs provide event multiplexing, derandomization, coincidence detection, and real-time rebinning. Embedded PC/104 microprocessors provide communication, real-time control, and configure the system. Extensive use of FPGAs make the overall design extremely flexible, allowing many different functions (or design modifications) to be realized without hardware changes. Incorporation of extensive onboard diagnostics, implemented in the FPGAs, is required by the very high level of integration and density achieved by this system.