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Unique Thermal Stability of Unnatural Hydrophobic Ds Bases in Double-Stranded DNAs.

PubMed

Kimoto, Michiko; Hirao, Ichiro

2017-10-20

Genetic alphabet expansion technology, the introduction of unnatural bases or base pairs into replicable DNA, has rapidly advanced as a new synthetic biology area. A hydrophobic unnatural base pair between 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and 2-nitro-4-propynylpyrrole (Px) exhibited high fidelity as a third base pair in PCR. SELEX methods using the Ds-Px pair enabled high-affinity DNA aptamer generation, and introducing a few Ds bases into DNA aptamers extremely augmented their affinities and selectivities to target proteins. Here, to further scrutinize the functions of this highly hydrophobic Ds base, the thermal stabilities of double-stranded DNAs (dsDNA) containing a noncognate Ds-Ds or G-Ds pair were examined. The thermal stability of the Ds-Ds self-pair was as high as that of the natural G-C pair, and apart from the generally higher stability of the G-C pair than that of the A-T pair, most of the 5'-pyrimidine-Ds-purine-3' sequences, such as CDsA and TDsA, exhibited higher stability than the 5'-purine-Ds-pyrimidine-3' sequences, such as GDsC and ADsC, in dsDNAs. This trait enabled the GC-content-independent control of the thermal stability of the designed dsDNA fragments. The melting temperatures of dsDNA fragments containing the Ds-Ds pair can be predicted from the nearest-neighbor parameters including the Ds base. In addition, the noncognate G-Ds pair can efficiently distinguish its neighboring cognate natural base pairs from noncognate pairs. We demonstrated that real-time PCR using primers containing Ds accurately detected a single-nucleotide mismatch in target DNAs. These unique properties of the Ds base that affect the stabilities of the neighboring base pairs could impart new functions to DNA molecules and technologies.

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Study of the Decay Bs0→Ds(*)Ds(*)

NASA Astrophysics Data System (ADS)

Abazov, V. M.; Abbott, B.; Abolins, M.; Acharya, B. S.; Adams, M.; Adams, T.; Aguilo, E.; Ahn, S. H.; Ahsan, M.; Alexeev, G. D.; Alkhazov, G.; Alton, A.; Alverson, G.; Alves, G. A.; Anastasoaie, M.; Ancu, L. S.; Andeen, T.; Anderson, S.; Andrieu, B.; Anzelc, M. S.; Arnoud, Y.; Arov, M.; Askew, A.; Åsman, B.; Assis Jesus, A. C. S.; Atramentov, O.; Autermann, C.; Avila, C.; Ay, C.; Badaud, F.; Baden, A.; Bagby, L.; Baldin, B.; Bandurin, D. V.; Banerjee, P.; Banerjee, S.; Barberis, E.; Barfuss, A.-F.; Bargassa, P.; Baringer, P.; Barreto, J.; Bartlett, J. F.; Bassler, U.; Bauer, D.; Beale, S.; Bean, A.; Begalli, M.; Begel, M.; Belanger-Champagne, C.; Bellantoni, L.; Bellavance, A.; Benitez, J. A.; Beri, S. B.; Bernardi, G.; Bernhard, R.; Berntzon, L.; Bertram, I.; Besançon, M.; Beuselinck, R.; Bezzubov, V. A.; Bhat, P. C.; Bhatnagar, V.; Binder, M.; Biscarat, C.; Blazey, G.; Blekman, F.; Blessing, S.; Bloch, D.; Bloom, K.; Boehnlein, A.; Boline, D.; Bolton, T. A.; Borissov, G.; Bos, K.; Bose, T.; Brandt, A.; Brock, R.; Brooijmans, G.; Bross, A.; Brown, D.; Buchanan, N. J.; Buchholz, D.; Buehler, M.; Buescher, V.; Burdin, S.; Burke, S.; Burnett, T. H.; Busato, E.; Buszello, C. P.; Butler, J. M.; Calfayan, P.; Calvet, S.; Cammin, J.; Caron, S.; Carvalho, W.; Casey, B. C. K.; Cason, N. M.; Castilla-Valdez, H.; Chakrabarti, S.; Chakraborty, D.; Chan, K.; Chan, K. M.; Chandra, A.; Charles, F.; Cheu, E.; Chevallier, F.; Cho, D. K.; Choi, S.; Choudhary, B.; Christofek, L.; Christoudias, T.; Cihangir, S.; Claes, D.; Clément, B.; Clément, C.; Coadou, Y.; Cooke, M.; Cooper, W. E.; Corcoran, M.; Couderc, F.; Cousinou, M.-C.; Crépé-Renaudin, S.; Cutts, D.; Ćwiok, M.; da Motta, H.; Das, A.; Davies, G.; de, K.; de Jong, P.; de Jong, S. J.; de La Cruz-Burelo, E.; de Oliveira Martins, C.; Degenhardt, J. D.; Déliot, F.; Demarteau, M.; Demina, R.; Denisov, D.; Denisov, S. P.; Desai, S.; Diehl, H. T.; Diesburg, M.; Dominguez, A.; Dong, H.; Dudko, L. V.; Duflot, L.; Dugad, S. R.; Duggan, D.; Duperrin, A.; Dyer, J.; Dyshkant, A.; Eads, M.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Enari, Y.; Eno, S.; Ermolov, P.; Evans, H.; Evdokimov, A.; Evdokimov, V. N.; Ferapontov, A. V.; Ferbel, T.; Fiedler, F.; Filthaut, F.; Fisher, W.; Fisk, H. E.; Ford, M.; Fortner, M.; Fox, H.; Fu, S.; Fuess, S.; Gadfort, T.; Galea, C. F.; Gallas, E.; Galyaev, E.; Garcia, C.; Garcia-Bellido, A.; Gavrilov, V.; Gay, P.; Geist, W.; Gelé, D.; Gerber, C. E.; Gershtein, Y.; Gillberg, D.; Ginther, G.; Gollub, N.; Gómez, B.; Goussiou, A.; Grannis, P. D.; Greenlee, H.; Greenwood, Z. D.; Gregores, E. M.; Grenier, G.; Gris, Ph.; Grivaz, J.-F.; Grohsjean, A.; Grünendahl, S.; Grünewald, M. W.; Guo, F.; Guo, J.; Gutierrez, G.; Gutierrez, P.; Haas, A.; Hadley, N. J.; Haefner, P.; Hagopian, S.; Haley, J.; Hall, I.; Hall, R. E.; Han, L.; Hanagaki, K.; Hansson, P.; Harder, K.; Harel, A.; Harrington, R.; Hauptman, J. M.; Hauser, R.; Hays, J.; Hebbeker, T.; Hedin, D.; Hegeman, J. G.; Heinmiller, J. M.; Heinson, A. P.; Heintz, U.; Hensel, C.; Herner, K.; Hesketh, G.; Hildreth, M. D.; Hirosky, R.; Hobbs, J. D.; Hoeneisen, B.; Hoeth, H.; Hohlfeld, M.; Hong, S. J.; Hooper, R.; Houben, P.; Hu, Y.; Hubacek, Z.; Hynek, V.; Iashvili, I.; Illingworth, R.; Ito, A. S.; Jabeen, S.; Jaffré, M.; Jain, S.; Jakobs, K.; Jarvis, C.; Jesik, R.; Johns, K.; Johnson, C.; Johnson, M.; Jonckheere, A.; Jonsson, P.; Juste, A.; Käfer, D.; Kahn, S.; Kajfasz, E.; Kalinin, A. M.; Kalk, J. M.; Kalk, J. R.; Kappler, S.; Karmanov, D.; Kasper, J.; Kasper, P.; Katsanos, I.; Kau, D.; Kaur, R.; Kaushik, V.; Kehoe, R.; Kermiche, S.; Khalatyan, N.; Khanov, A.; Kharchilava, A.; Kharzheev, Y. M.; Khatidze, D.; Kim, H.; Kim, T. J.; Kirby, M. H.; Klima, B.; Kohli, J. M.; Konrath, J.-P.; Kopal, M.; Korablev, V. M.; Kotcher, J.; Kothari, B.; Koubarovsky, A.; Kozelov, A. V.; Krop, D.; Kryemadhi, A.; Kuhl, T.; Kumar, A.; Kunori, S.; Kupco, A.; Kurča, T.; Kvita, J.; Lam, D.; Lammers, S.; Landsberg, G.; Lazoflores, J.; Lebrun, P.; Lee, W. M.; Leflat, A.; Lehner, F.; Lesne, V.; Leveque, J.; Lewis, P.; Li, J.; Li, L.; Li, Q. Z.; Lietti, S. M.; Lima, J. G. R.; Lincoln, D.; Linnemann, J.; Lipaev, V. V.; Lipton, R.; Liu, Z.; Lobo, L.; Lobodenko, A.; Lokajicek, M.; Lounis, A.; Love, P.; Lubatti, H. J.; Lynker, M.; Lyon, A. L.; Maciel, A. K. A.; Madaras, R. J.; Mättig, P.; Magass, C.; Magerkurth, A.; Makovec, N.; Mal, P. K.; Malbouisson, H. B.; Malik, S.; Malyshev, V. L.; Mao, H. S.; Maravin, Y.; Martin, B.; McCarthy, R.; Melnitchouk, A.; Mendes, A.; Mendoza, L.; Mercadante, P. G.; Merkin, M.; Merritt, K. W.; Meyer, A.; Meyer, J.; Michaut, M.; Miettinen, H.; Millet, T.; Mitrevski, J.; Molina, J.; Mommsen, R. K.; Mondal, N. K.; Monk, J.; Moore, R. W.; Moulik, T.; Muanza, G. S.; Mulders, M.; Mulhearn, M.; Mundal, O.; Mundim, L.; Nagy, E.; Naimuddin, M.; Narain, M.; Naumann, N. A.; Neal, H. A.; Negret, J. P.; Neustroev, P.; Nilsen, H.; Noeding, C.; Nomerotski, A.; Novaes, S. F.; Nunnemann, T.; O'Dell, V.; O'Neil, D. C.; Obrant, G.; Ochando, C.; Oguri, V.; Oliveira, N.; Onoprienko, D.; Oshima, N.; Osta, J.; Otec, R.; Otero Y Garzón, G. J.; Owen, M.; Padley, P.; Pangilinan, M.; Parashar, N.; Park, S.-J.; Park, S. K.; Parsons, J.; Partridge, R.; Parua, N.; Patwa, A.; Pawloski, G.; Perea, P. M.; Peters, K.; Peters, Y.; Pétroff, P.; Petteni, M.; Piegaia, R.; Piper, J.; Pleier, M.-A.; Podesta-Lerma, P. L. M.; Podstavkov, V. M.; Pogorelov, Y.; Pol, M.-E.; Pompoš, A.; Pope, B. G.; Popov, A. V.; Potter, C.; Prado da Silva, W. L.; Prosper, H. B.; Protopopescu, S.; Qian, J.; Quadt, A.; Quinn, B.; Rangel, M. S.; Rani, K. J.; Ranjan, K.; Ratoff, P. N.; Renkel, P.; Reucroft, S.; Rijssenbeek, M.; Ripp-Baudot, I.; Rizatdinova, F.; Robinson, S.; Rodrigues, R. F.; Royon, C.; Rubinov, P.; Ruchti, R.; Sajot, G.; Sánchez-Hernández, A.; Sanders, M. P.; Santoro, A.; Savage, G.; Sawyer, L.; Scanlon, T.; Schaile, D.; Schamberger, R. D.; Scheglov, Y.; Schellman, H.; Schieferdecker, P.; Schmitt, C.; Schwanenberger, C.; Schwartzman, A.; Schwienhorst, R.; Sekaric, J.; Sengupta, S.; Severini, H.; Shabalina, E.; Shamim, M.; Shary, V.; Shchukin, A. A.; Shivpuri, R. K.; Shpakov, D.; Siccardi, V.; Sidwell, R. A.; Simak, V.; Sirotenko, V.; Skubic, P.; Slattery, P.; Smirnov, D.; Smith, R. P.; Snow, G. R.; Snow, J.; Snyder, S.; Söldner-Rembold, S.; Sonnenschein, L.; Sopczak, A.; Sosebee, M.; Soustruznik, K.; Souza, M.; Spurlock, B.; Stark, J.; Steele, J.; Stolin, V.; Stoyanova, D. A.; Strandberg, J.; Strandberg, S.; Strang, M. A.; Strauss, M.; Ströhmer, R.; Strom, D.; Strovink, M.; Stutte, L.; Sumowidagdo, S.; Svoisky, P.; Sznajder, A.; Talby, M.; Tamburello, P.; Tanasijczuk, A.; Taylor, W.; Telford, P.; Temple, J.; Tiller, B.; Tissandier, F.; Titov, M.; Tokmenin, V. V.; Tomoto, M.; Toole, T.; Torchiani, I.; Trefzger, T.; Trincaz-Duvoid, S.; Tsybychev, D.; Tuchming, B.; Tully, C.; Tuts, P. M.; Unalan, R.; Uvarov, L.; Uvarov, S.; Uzunyan, S.; Vachon, B.; van den Berg, P. J.; van Eijk, B.; van Kooten, R.; van Leeuwen, W. M.; Varelas, N.; Varnes, E. W.; Vartapetian, A.; Vasilyev, I. A.; Vaupel, M.; Verdier, P.; Vertogradov, L. S.; Verzocchi, M.; Villeneuve-Seguier, F.; Vint, P.; Vlimant, J.-R.; von Toerne, E.; Voutilainen, M.; Vreeswijk, M.; Wahl, H. D.; Walder, J.; Wang, L.; Wang, M. H. L. S.; Warchol, J.; Watts, G.; Wayne, M.; Weber, G.; Weber, M.; Weerts, H.; Wenger, A.; Wermes, N.; Wetstein, M.; White, A.; Wicke, D.; Wilson, G. W.; Wimpenny, S. J.; Wobisch, M.; Wood, D. R.; Wyatt, T. R.; Xie, Y.; Yacoob, S.; Yamada, R.; Yan, M.; Yasuda, T.; Yatsunenko, Y. A.; Yip, K.; Yoo, H. D.; Youn, S. W.; Yu, C.; Yu, J.; Yurkewicz, A.; Zatserklyaniy, A.; Zeitnitz, C.; Zhang, D.; Zhao, T.; Zhou, B.; Zhu, J.; Zielinski, M.; Zieminska, D.; Zieminski, A.; Zutshi, V.; Zverev, E. G.

2007-12-01

We report a study of the decay Bs0→Ds(*)Ds(*) using a data sample corresponding to 1.3fb-1 of integrated luminosity collected by the D0 experiment in 2002 2006 during run II of the Fermilab Tevatron collider. One Ds(*) meson was partially reconstructed in the decay Ds→ϕμν, and the other Ds(*) meson was identified using the decay Ds→ϕπ where no attempt was made to distinguish Ds and Ds* states. For the branching fraction Br(Bs0→Ds(*)Ds(*)) we obtain a 90% C.L. range [0.002,0.080] and central value 0.039-0.017+0.019(stat)-0.015+0.016(syst). This was subsequently used to make the most precise estimate of the width difference ΔΓsCP in the Bs0-B¯s0 system: ΔΓsCP/Γs=0.079-0.035+0.038(stat)-0.030+0.031(syst).

Real-Time Multi-Target Localization from Unmanned Aerial Vehicles

PubMed Central

Wang, Xuan; Liu, Jinghong; Zhou, Qianfei

2016-01-01

In order to improve the reconnaissance efficiency of unmanned aerial vehicle (UAV) electro-optical stabilized imaging systems, a real-time multi-target localization scheme based on an UAV electro-optical stabilized imaging system is proposed. First, a target location model is studied. Then, the geodetic coordinates of multi-targets are calculated using the homogeneous coordinate transformation. On the basis of this, two methods which can improve the accuracy of the multi-target localization are proposed: (1) the real-time zoom lens distortion correction method; (2) a recursive least squares (RLS) filtering method based on UAV dead reckoning. The multi-target localization error model is established using Monte Carlo theory. In an actual flight, the UAV flight altitude is 1140 m. The multi-target localization results are within the range of allowable error. After we use a lens distortion correction method in a single image, the circular error probability (CEP) of the multi-target localization is reduced by 7%, and 50 targets can be located at the same time. The RLS algorithm can adaptively estimate the location data based on multiple images. Compared with multi-target localization based on a single image, CEP of the multi-target localization using RLS is reduced by 25%. The proposed method can be implemented on a small circuit board to operate in real time. This research is expected to significantly benefit small UAVs which need multi-target geo-location functions. PMID:28029145

Real-Time Multi-Target Localization from Unmanned Aerial Vehicles.

PubMed

Wang, Xuan; Liu, Jinghong; Zhou, Qianfei

2016-12-25

In order to improve the reconnaissance efficiency of unmanned aerial vehicle (UAV) electro-optical stabilized imaging systems, a real-time multi-target localization scheme based on an UAV electro-optical stabilized imaging system is proposed. First, a target location model is studied. Then, the geodetic coordinates of multi-targets are calculated using the homogeneous coordinate transformation. On the basis of this, two methods which can improve the accuracy of the multi-target localization are proposed: (1) the real-time zoom lens distortion correction method; (2) a recursive least squares (RLS) filtering method based on UAV dead reckoning. The multi-target localization error model is established using Monte Carlo theory. In an actual flight, the UAV flight altitude is 1140 m. The multi-target localization results are within the range of allowable error. After we use a lens distortion correction method in a single image, the circular error probability (CEP) of the multi-target localization is reduced by 7%, and 50 targets can be located at the same time. The RLS algorithm can adaptively estimate the location data based on multiple images. Compared with multi-target localization based on a single image, CEP of the multi-target localization using RLS is reduced by 25%. The proposed method can be implemented on a small circuit board to operate in real time. This research is expected to significantly benefit small UAVs which need multi-target geo-location functions.

Non-target Effects of Green Fluorescent Protein (GFP)-derived Double-Stranded RNA (dsRNA-GFP) Used in Honey Bee RNA Interference (RNAi) Assays

PubMed Central

Nunes, Francis M. F.; Aleixo, Aline C.; Barchuk, Angel R.; Bomtorin, Ana D.; Grozinger, Christina M.; Simões, Zilá L. P.

2013-01-01

RNA interference has been frequently applied to modulate gene function in organisms where the production and maintenance of mutants is challenging, as in our model of study, the honey bee, Apis mellifera. A green fluorescent protein (GFP)-derived double-stranded RNA (dsRNA-GFP) is currently commonly used as control in honey bee RNAi experiments, since its gene does not exist in the A. mellifera genome. Although dsRNA-GFP is not expected to trigger RNAi responses in treated bees, undesirable effects on gene expression, pigmentation or developmental timing are often observed. Here, we performed three independent experiments using microarrays to examine the effect of dsRNA-GFP treatment (introduced by feeding) on global gene expression patterns in developing worker bees. Our data revealed that the expression of nearly 1,400 genes was altered in response to dsRNA-GFP, representing around 10% of known honey bee genes. Expression changes appear to be the result of both direct off-target effects and indirect downstream secondary effects; indeed, there were several instances of sequence similarity between putative siRNAs generated from the dsRNA-GFP construct and genes whose expression levels were altered. In general, the affected genes are involved in important developmental and metabolic processes associated with RNA processing and transport, hormone metabolism, immunity, response to external stimulus and to stress. These results suggest that multiple dsRNA controls should be employed in RNAi studies in honey bees. Furthermore, any RNAi studies involving these genes affected by dsRNA-GFP in our studies should use a different dsRNA control. PMID:26466797

Non-Target Effects of Green Fluorescent Protein (GFP)-Derived Double-Stranded RNA (dsRNA-GFP) Used in Honey Bee RNA Interference (RNAi) Assays.

PubMed

Nunes, Francis M F; Aleixo, Aline C; Barchuk, Angel R; Bomtorin, Ana D; Grozinger, Christina M; Simões, Zilá L P

2013-01-04

RNA interference has been frequently applied to modulate gene function in organisms where the production and maintenance of mutants is challenging, as in our model of study, the honey bee, Apis mellifera. A green fluorescent protein (GFP)-derived double-stranded RNA (dsRNA-GFP) is currently commonly used as control in honey bee RNAi experiments, since its gene does not exist in the A. mellifera genome. Although dsRNA-GFP is not expected to trigger RNAi responses in treated bees, undesirable effects on gene expression, pigmentation or developmental timing are often observed. Here, we performed three independent experiments using microarrays to examine the effect of dsRNA-GFP treatment (introduced by feeding) on global gene expression patterns in developing worker bees. Our data revealed that the expression of nearly 1,400 genes was altered in response to dsRNA-GFP, representing around 10% of known honey bee genes. Expression changes appear to be the result of both direct off-target effects and indirect downstream secondary effects; indeed, there were several instances of sequence similarity between putative siRNAs generated from the dsRNA-GFP construct and genes whose expression levels were altered. In general, the affected genes are involved in important developmental and metabolic processes associated with RNA processing and transport, hormone metabolism, immunity, response to external stimulus and to stress. These results suggest that multiple dsRNA controls should be employed in RNAi studies in honey bees. Furthermore, any RNAi studies involving these genes affected by dsRNA-GFP in our studies should use a different dsRNA control.

Smart filters: from VIS/NIR to MW/LWIR protection

NASA Astrophysics Data System (ADS)

Donval, Ariela; Fisher, Tali; Lipman, Ofir; Oron, Moshe

2014-06-01

New development of imaging systems implies the use of multi band wavelength, VIS and IR, for imaging enhancement and more data presenting. Some of those systems, such as target identification and tracking can unintentionally result in a laser beam reflected back into the sensor, leading to transient dazzling or permanent damage of the sensor. We propose a novel passive Wideband Protection Filter (WPF) that blocks the transmission only if the power exceeds a certain threshold. We present a special design of WPF suitable for dual- and multi- band wavelength range, including transmission and functionality performances. We demonstrate a new design transferring our WPF filter from VIS/NIR into the MW/LWIR.

Multi-Target Regression via Robust Low-Rank Learning.

PubMed

Zhen, Xiantong; Yu, Mengyang; He, Xiaofei; Li, Shuo

2018-02-01

Multi-target regression has recently regained great popularity due to its capability of simultaneously learning multiple relevant regression tasks and its wide applications in data mining, computer vision and medical image analysis, while great challenges arise from jointly handling inter-target correlations and input-output relationships. In this paper, we propose Multi-layer Multi-target Regression (MMR) which enables simultaneously modeling intrinsic inter-target correlations and nonlinear input-output relationships in a general framework via robust low-rank learning. Specifically, the MMR can explicitly encode inter-target correlations in a structure matrix by matrix elastic nets (MEN); the MMR can work in conjunction with the kernel trick to effectively disentangle highly complex nonlinear input-output relationships; the MMR can be efficiently solved by a new alternating optimization algorithm with guaranteed convergence. The MMR leverages the strength of kernel methods for nonlinear feature learning and the structural advantage of multi-layer learning architectures for inter-target correlation modeling. More importantly, it offers a new multi-layer learning paradigm for multi-target regression which is endowed with high generality, flexibility and expressive ability. Extensive experimental evaluation on 18 diverse real-world datasets demonstrates that our MMR can achieve consistently high performance and outperforms representative state-of-the-art algorithms, which shows its great effectiveness and generality for multivariate prediction.

Down syndrome and leukemia: insights into leukemogenesis and translational targets

PubMed Central

Barbaric, Draga; Byatt, Sally-Anne; Sutton, Rosemary; Marshall, Glenn M.

2015-01-01

Children with Down syndrome (DS) have a significantly increased risk of childhood leukemia, in particular acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (DS-ALL). A pre-leukemia, called transient myeloproliferative disorder (TMD), characterised by a GATA binding protein 1 (GATA1) mutation, affects up to 30% of newborns with DS. In most cases, the pre-leukemia regresses spontaneously, however one-quarter of these children will go on to develop AMKL or myelodysplastic syndrome (MDS) . AMKL and MDS occurring in young children with DS and a GATA1 somatic mutation are collectively termed myeloid leukemia of Down syndrome (ML-DS). This model represents an important multi-step process of leukemogenesis, and further study is required to identify therapeutic targets to potentially prevent development of leukemia. DS-ALL is a high-risk leukemia and mutations in the JAK-STAT pathway are frequently observed. JAK inhibitors may improve outcome for this type of leukemia. Genetic and epigenetic studies have revealed likely candidate drivers involved in development of ML-DS and DS-ALL. Overall this review aims to identify potential impacts of new research on how we manage children with DS, pre-leukemia and leukemia. PMID:26835364

Study of radially excited Ds(21 S 0) and Ds(3P)

NASA Astrophysics Data System (ADS)

Tian, Yu; Zhao, Ze; Zhang, Ai-Lin

2017-08-01

The unobserved JP = 0- radial excitation Ds(21 S 0) is anticipated to have mass 2650 MeV (denoted as Ds(2650)). Study of hadronic production is an important way to identify highly excited states. We study hadronic production of Ds(2650) from higher excited resonances in a 3 P 0 model. Relevant hadronic partial decay widths are found to be very small, which implies it is difficult to observe Ds(2650) in hadronic decays of higher excited resonances. Hadronic decay widths of radially excited Ds(3P) have also been estimated. The total decay widths of four Ds(3P) are large, but the branching ratios in the Ds(2650)η channel are very small, which implies that it seems impossible to observe Ds(2650) in hadronic decays of Ds(3P). The dominant decay channels of the four Ds(3P) have been pointed out, and D1(2420), D1(2430), , D(2550), D(2600), (11D2)D(2750) and are possible to observe in hadronic production from Ds(3P). Supported by National Natural Science Foundation of China (11475111)

Measurement of B(Ds+→l+ν) and the decay constant fDS+

NASA Astrophysics Data System (ADS)

Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Aquines, O.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Butt, J.; Khalil, S.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.

2007-10-01

We examine e+e-→Ds-Ds*+ and Ds*-Ds+ interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fDs+. We use the Ds+→ℓ+ν channel, where the ℓ+ designates either a μ+ or a τ+, when the τ+→π+ν¯. Analyzing both modes independently, we determine B(Ds+→μ+ν)=(0.594±0.066±0.031)%, and B(Ds+→τ+ν)=(8.0±1.3±0.4)%. We also analyze them simultaneously to find an effective value of Beff(Ds+→μ+ν)=(0.638±0.059±0.033)% and extract fDs+=274±13±7MeV. Combining with our previous determination of B(D+→μ+ν), we also find the ratio fDs+/fD+=1.23±0.11±0.04. We compare to current theoretical estimates. Finally, we find B(Ds+→e+ν)<1.3×10-4 at 90% confidence level.

Screening the ToxCast Phase II library for acute neurotoxicity using cortical neurons grown on multi-well microelectrode array (mwMEA) plates

EPA Science Inventory

We have used primary cortical neurons grown in multi-well microelectrode array (mwMEA) plates to screen the ToxCast Phase II library of 1055 unique compounds for the ability to cause acute neurotoxicity. Each compound was screened at a single high concentration of 40 µM...

The Human Kinome Targeted by FDA Approved Multi-Target Drugs and Combination Products: A Comparative Study from the Drug-Target Interaction Network Perspective.

PubMed

Li, Ying Hong; Wang, Pan Pan; Li, Xiao Xu; Yu, Chun Yan; Yang, Hong; Zhou, Jin; Xue, Wei Wei; Tan, Jun; Zhu, Feng

2016-01-01

The human kinome is one of the most productive classes of drug target, and there is emerging necessity for treating complex diseases by means of polypharmacology (multi-target drugs and combination products). However, the advantages of the multi-target drugs and the combination products are still under debate. A comparative analysis between FDA approved multi-target drugs and combination products, targeting the human kinome, was conducted by mapping targets onto the phylogenetic tree of the human kinome. The approach of network medicine illustrating the drug-target interactions was applied to identify popular targets of multi-target drugs and combination products. As identified, the multi-target drugs tended to inhibit target pairs in the human kinome, especially the receptor tyrosine kinase family, while the combination products were able to against targets of distant homology relationship. This finding asked for choosing the combination products as a better solution for designing drugs aiming at targets of distant homology relationship. Moreover, sub-networks of drug-target interactions in specific disease were generated, and mechanisms shared by multi-target drugs and combination products were identified. In conclusion, this study performed an analysis between approved multi-target drugs and combination products against the human kinome, which could assist the discovery of next generation polypharmacology.

Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods.

PubMed

Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J

2017-03-03

We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods

PubMed Central

Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J.

2017-01-01

We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter. PMID:28273796

Multi-Hop Link Capacity of Multi-Route Multi-Hop MRC Diversity for a Virtual Cellular Network

NASA Astrophysics Data System (ADS)

Daou, Imane; Kudoh, Eisuke; Adachi, Fumiyuki

In virtual cellular network (VCN), proposed for high-speed mobile communications, the signal transmitted from a mobile terminal is received by some wireless ports distributed in each virtual cell and relayed to the central port that acts as a gateway to the core network. In this paper, we apply the multi-route MHMRC diversity in order to decrease the transmit power and increase the multi-hop link capacity. The transmit power, the interference power and the link capacity are evaluated for DS-CDMA multi-hop VCN by computer simulation. The multi-route MHMRC diversity can be applied to not only DS-CDMA but also other access schemes (i. e. MC-CDMA, OFDM, etc.).

Characterization of ToxCast Phase II compounds disruption of spontaneous network activity in cortical networks grown on multi-well microelectrode array (mwMEA) plates.

EPA Science Inventory

The development of multi-well microelectrode array (mwMEA) systems has increased in vitro screening throughput making them an effective method to screen and prioritize large sets of compounds for potential neurotoxicity. In the present experiments, a multiplexed approach was used...

Multi-Wavelength Q-Switched Ytterbium-Doped Fiber Laser with Multi-Walled Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Al-Masoodi, A. H. H.; Ahmed, M. H. M.; Arof, H.; Harun, S. W.

2018-03-01

We demonstrate a passively multi-wavelength Q-switched Ytterbium-doped fiber laser (YDFL) based on a multi-wall carbon nanotubes embedded in polyethylene oxide film as saturable absorber. The YDFL generates a stable multi-wavelength with spacing of 1.9 nm as the 980 nm pump power is fixed within 62. 4 mW and 78.0 mW. The repetition rate of the laser is tunable from 10.41 to 29.04 kHz by increasing the pump power from the threshold power of 62.4 mW to 78 mW. At 78 mW pump power, the maximum pulse energy of 38 nJ and the shortest pulse width of 8.87 µs are obtained.

Multi-Robot, Multi-Target Particle Swarm Optimization Search in Noisy Wireless Environments

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

Kurt Derr; Milos Manic

Multiple small robots (swarms) can work together using Particle Swarm Optimization (PSO) to perform tasks that are difficult or impossible for a single robot to accomplish. The problem considered in this paper is exploration of an unknown environment with the goal of finding a target(s) at an unknown location(s) using multiple small mobile robots. This work demonstrates the use of a distributed PSO algorithm with a novel adaptive RSS weighting factor to guide robots for locating target(s) in high risk environments. The approach was developed and analyzed on multiple robot single and multiple target search. The approach was further enhancedmore » by the multi-robot-multi-target search in noisy environments. The experimental results demonstrated how the availability of radio frequency signal can significantly affect robot search time to reach a target.« less

First observation of the decay Bs0-->Ds-Ds+ and measurement of its branching ratio.

PubMed

Aaltonen, T; Adelman, J; Akimoto, T; Albrow, M G; Alvarez González, B; Amerio, S; Amidei, D; Anastassov, A; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Apresyan, A; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Bednar, P; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Bridgeman, A; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carlsmith, D; Carosi, R; Carrillo, S; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; Dagenhart, D; Datta, M; Davies, T; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Ferrazza, C; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garberson, F; Garcia, J E; Garfinkel, A F; Gerberich, H; Gerdes, D; Giagu, S; Giakoumopolou, V; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C M; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hewamanage, S; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Kar, D; Karchin, P E; Kato, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Koay, S A; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; Lecompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Linacre, J; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lovas, L; Lu, R-S; Lucchesi, D; Lueck, J; Luci, C; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; Macqueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Mattson, M E; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyake, H; Moed, S; Moggi, N; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagai, Y; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norman, M; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagan Griso, S; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyria, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Thom, J; Thompson, A S; Thompson, G A; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vázquez, F; Velev, G; Vellidis, C; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner-Kuhr, J; Wagner, W; Wakisaka, T; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zheng, Y; Zucchelli, S

2008-01-18

We report the observation of the exclusive decay Bs0-->Ds-Ds+ at the 7.5 standard deviation level using 355 pb(-1) of data collected by the CDF II detector in pp collisions at sqrt[s]=1.96 TeV at the Fermilab Tevatron. We measure the relative branching ratio B(Bs0-->Ds-Ds+)/B(B0-->D-Ds+)=1.44(-0.44)(+0.48). Using the world average value for B(B0-->D-Ds+), we find B(Bs0-->Ds-Ds+)=(9.4(-4.2)(+4.4))x10(-3). This provides a lower bound DeltaGammasCP/Gammas>or=2B(Bs0-->Ds-Ds+)>1.2x10(-2) at 95% C.L.

The Effects of Spatial Diversity and Imperfect Channel Estimation on Wideband MC-DS-CDMA and MC-CDMA

DTIC Science & Technology

2009-10-01

In our previous work, we compared the theoretical bit error rates of multi-carrier direct sequence code division multiple access (MC- DS - CDMA ) and...consider only those cases where MC- CDMA has higher frequency diversity than MC- DS - CDMA . Since increases in diversity yield diminishing gains, we conclude

Dietary Risk Assessment of v-ATPase A dsRNAs on Monarch Butterfly Larvae.

PubMed

Pan, Huipeng; Yang, Xiaowei; Bidne, Keith; Hellmich, Richard L; Siegfried, Blair D; Zhou, Xuguo

2017-01-01

By suppressing the expression of genes with essential biological functions, in planta RNAi can negatively affect the development and survival of target pests. As a part of a concerted effort to assess the risks of RNAi transgenic crops on non-target organisms, we developed an in vivo toxicity assay to examine the impacts of ingested dsRNAs incurred to the monarch butterfly, Danaus plexippus (L.), an iconic eco-indicator in North America. To create the worst case scenario, the full-length v-ATPase A cDNAs from the target pest, western corn rootworm, Diabrotica virgifera virgifera , and the non-target D. plexippus were respectively cloned. A 400 bp fragment with the highest sequence similarity between the two species was used as the template to synthesize dsRNAs for the subsequent dietary RNAi toxicity assay. Specifically, newly hatched neonates were provisioned with leaf disks surface-coated with v-ATPase A dsRNAs synthesized from D. v. virgifera and D. plexippus , respectively, a control dsRNA, β -glucoruronidase , from plants, and H 2 O. The endpoint measurements included gene expressions and life history traits. The 2283 bp D. plexippus v-ATPase A cDNA contains a 99 bp 5'-untranslated region, a 330 bp 3'-untranslated region, and an 1851 bp ORF encoding 617 amino acids. The temporal RNAi study did not detect any impact to D. plexippus v-ATPase A expression by the assay days and treatments. This was reflected in the phenotypic impacts of dietary RNAi, in which both survival rate and development time were not affected by the uptake of ingested dsRNAs. These combined results suggest that D. plexippus larvae are not susceptible to dietary RNAi, therefore, the impact of transgenic RNAi plants on this non-target organism is, likely, negligible.

Measurement of the Decay Constant fDs+ Using Ds+→l+ν

NASA Astrophysics Data System (ADS)

Artuso, M.; Blusk, S.; Butt, J.; Khalil, S.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Pivarski, J.; Riley, D.; Ryd, A.; Sadoff, A. J.; Schwarthoff, H.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Cawlfield, C.; Eisenstein, B. I.; Karliner, I.; Kim, D.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Smith, A.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Aquines, O.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Huang, G. S.; Miller, D. H.; Pavlunin, V.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.

2007-08-01

We measure the decay constant fDs+ using the Ds+→ℓ+ν channel, where the ℓ+ designates either a μ+ or a τ+, when the τ+→π+ν¯. Using both measurements we find fDs+=274±13±7MeV. Combining with our previous determination of fD+, we compute the ratio fDs+/fD+=1.23±0.11±0.04. We compare with theoretical estimates.

The Activating Human NK Cell Receptor KIR2DS2 Recognizes a β2-Microglobulin-Independent Ligand on Cancer Cells.

PubMed

Thiruchelvam-Kyle, Lavanya; Hoelsbrekken, Sigurd E; Saether, Per C; Bjørnsen, Elisabeth Gyllensten; Pende, Daniela; Fossum, Sigbjørn; Daws, Michael R; Dissen, Erik

2017-04-01

The functions of activating members of the killer cell Ig-like receptor (KIR) family are not fully understood, as the ligands for these receptors are largely unidentified. In this study, we report that KIR2DS2 reporter cells recognize a ligand expressed by cancer cell lines. All cancer targets recognized by KIR2DS2 were also recognized by KIR2DL2 and KIR2DL3 reporters. Trogocytosis of membrane proteins from the cancer targets was observed with responding reporter cells, indicating the formation of KIR2DS2 ligand-specific immunological synapses. HLA-C typing of target cells showed that KIR2DS2 recognition was independent of the HLA C1 or C2 group, whereas targets cells that were only recognized by KIR2DL3 expressed C1 group alleles. Anti-HLA class I Abs blocked KIR2DL3 responses toward C1-expressing targets, but they did not block KIR2DS2 recognition of cancer cells. Small interfering RNA knockdown of β 2 -microglobulin reduced the expression of class I H chain on the cancer targets by >97%, but it did not reduce the KIR2DS2 reporter responses, indicating a β 2 -microglobulin-independent ligand for KIR2DS2. Importantly, KIR2DL3 responses toward some KIR2DS2 ligand-expressing cells were also undiminished after β 2 -microglobulin knockdown, and they were not blocked by anti-HLA class I Abs, suggesting that KIR2DL3, in addition to the traditional HLA-C ligands, can bind to the same β 2 -microglobulin-independent ligand as KIR2DS2. These observations indicate the existence of a novel, presently uncharacterized ligand for the activating NK cell receptor KIR2DS2. Molecular identification of this ligand may lead to improved KIR-HLA mismatching in hematopoietic stem cell transplantation therapy for leukemia and new, more specific NK cell-based cancer therapies. Copyright © 2017 by The American Association of Immunologists, Inc.

Multi-Source Multi-Target Dictionary Learning for Prediction of Cognitive Decline

PubMed Central

Zhang, Jie; Li, Qingyang; Caselli, Richard J.; Thompson, Paul M.; Ye, Jieping; Wang, Yalin

2017-01-01

Alzheimer’s Disease (AD) is the most common type of dementia. Identifying correct biomarkers may determine pre-symptomatic AD subjects and enable early intervention. Recently, Multi-task sparse feature learning has been successfully applied to many computer vision and biomedical informatics researches. It aims to improve the generalization performance by exploiting the shared features among different tasks. However, most of the existing algorithms are formulated as a supervised learning scheme. Its drawback is with either insufficient feature numbers or missing label information. To address these challenges, we formulate an unsupervised framework for multi-task sparse feature learning based on a novel dictionary learning algorithm. To solve the unsupervised learning problem, we propose a two-stage Multi-Source Multi-Target Dictionary Learning (MMDL) algorithm. In stage 1, we propose a multi-source dictionary learning method to utilize the common and individual sparse features in different time slots. In stage 2, supported by a rigorous theoretical analysis, we develop a multi-task learning method to solve the missing label problem. Empirical studies on an N = 3970 longitudinal brain image data set, which involves 2 sources and 5 targets, demonstrate the improved prediction accuracy and speed efficiency of MMDL in comparison with other state-of-the-art algorithms. PMID:28943731

Multi-Source Multi-Target Dictionary Learning for Prediction of Cognitive Decline.

PubMed

Zhang, Jie; Li, Qingyang; Caselli, Richard J; Thompson, Paul M; Ye, Jieping; Wang, Yalin

2017-06-01

Alzheimer's Disease (AD) is the most common type of dementia. Identifying correct biomarkers may determine pre-symptomatic AD subjects and enable early intervention. Recently, Multi-task sparse feature learning has been successfully applied to many computer vision and biomedical informatics researches. It aims to improve the generalization performance by exploiting the shared features among different tasks. However, most of the existing algorithms are formulated as a supervised learning scheme. Its drawback is with either insufficient feature numbers or missing label information. To address these challenges, we formulate an unsupervised framework for multi-task sparse feature learning based on a novel dictionary learning algorithm. To solve the unsupervised learning problem, we propose a two-stage Multi-Source Multi-Target Dictionary Learning (MMDL) algorithm. In stage 1, we propose a multi-source dictionary learning method to utilize the common and individual sparse features in different time slots. In stage 2, supported by a rigorous theoretical analysis, we develop a multi-task learning method to solve the missing label problem. Empirical studies on an N = 3970 longitudinal brain image data set, which involves 2 sources and 5 targets, demonstrate the improved prediction accuracy and speed efficiency of MMDL in comparison with other state-of-the-art algorithms.

The role of multi-target policy instruments in agri-environmental policy mixes.

PubMed

Schader, Christian; Lampkin, Nicholas; Muller, Adrian; Stolze, Matthias

2014-12-01

The Tinbergen Rule has been used to criticise multi-target policy instruments for being inefficient. The aim of this paper is to clarify the role of multi-target policy instruments using the case of agri-environmental policy. Employing an analytical linear optimisation model, this paper demonstrates that there is no general contradiction between multi-target policy instruments and the Tinbergen Rule, if multi-target policy instruments are embedded in a policy-mix with a sufficient number of targeted instruments. We show that the relation between cost-effectiveness of the instruments, related to all policy targets, is the key determinant for an economically sound choice of policy instruments. If economies of scope with respect to achieving policy targets are realised, a higher cost-effectiveness of multi-target policy instruments can be achieved. Using the example of organic farming support policy, we discuss several reasons why economies of scope could be realised by multi-target agri-environmental policy instruments. Copyright © 2014 Elsevier Ltd. All rights reserved.

Designing multi-targeted agents: An emerging anticancer drug discovery paradigm.

PubMed

Fu, Rong-Geng; Sun, Yuan; Sheng, Wen-Bing; Liao, Duan-Fang

2017-08-18

The dominant paradigm in drug discovery is to design ligands with maximum selectivity to act on individual drug targets. With the target-based approach, many new chemical entities have been discovered, developed, and further approved as drugs. However, there are a large number of complex diseases such as cancer that cannot be effectively treated or cured only with one medicine to modulate the biological function of a single target. As simultaneous intervention of two (or multiple) cancer progression relevant targets has shown improved therapeutic efficacy, the innovation of multi-targeted drugs has become a promising and prevailing research topic and numerous multi-targeted anticancer agents are currently at various developmental stages. However, most multi-pharmacophore scaffolds are usually discovered by serendipity or screening, while rational design by combining existing pharmacophore scaffolds remains an enormous challenge. In this review, four types of multi-pharmacophore modes are discussed, and the examples from literature will be used to introduce attractive lead compounds with the capability of simultaneously interfering with different enzyme or signaling pathway of cancer progression, which will reveal the trends and insights to help the design of the next generation multi-targeted anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Delivery of lethal dsRNAs in insect diets by branched amphiphilic peptide capsules.

PubMed

Avila, L A; Chandrasekar, R; Wilkinson, K E; Balthazor, J; Heerman, M; Bechard, J; Brown, S; Park, Y; Dhar, S; Reeck, G R; Tomich, J M

2018-03-10

Development of new and specific insect pest management methods is critical for overcoming pesticide resistance and collateral off-target killings. Gene silencing by feeding dsRNA to insects shows promise in this area. Here we described the use of a peptide nano-material, branched amphiphilic peptide capsules (BAPCs), that facilitates cellular uptake of dsRNA by insects through feeding. The insect diets included dsRNA with and without complexation with BAPCs. The selected insect species come from two different orders with different feeding mechanisms: Tribolium castaneum and Acyrthosiphon pisum. The gene transcripts tested (BiP and Armet) are part of the unfolded protein response (UPR) and suppressing their translation resulted in lethality. For Acyrthosiphon pisum, ingestion of BiP-dsRNA associated with BAPCs led to the premature death of the aphids (t 1/2 =4-5days) compared to ingestion of the same amounts of free BiP-dsRNA (t 1/2 =11-12days). Tribolium castaneum was effectively killed using a combination of BiP-dsRNA and Armet-dsRNA complexed with BAPCs; most dying as larvae or during eclosion (~75%). Feeding dsRNA alone resulted in fewer deaths (~30%). The results show that complexation of dsRNA with BAPCs enhanced the oral delivery of dsRNA over dsRNA alone. Copyright © 2018 Elsevier B.V. All rights reserved.

R&D of A MW-class solid-target for a spallation neutron source

NASA Astrophysics Data System (ADS)

Kawai, Masayoshi; Furusaka, Michihiro; Kikuchi, Kenji; Kurishita, Hiroaki; Watanabe, Ryuzo; Li, Jing-Feng; Sugimoto, Katsuhisa; Yamamura, Tsutomu; Hiraoka, Yutaka; Abe, Katsunori; Hasegawa, Akira; Yoshiie, Masatoshi; Takenaka, Hiroyuki; Mishima, Katsuichiro; Kiyanagi, Yoshiaki; Tanabe, Tetsuo; Yoshida, Naoaki; Igarashi, Tadashi

2003-05-01

R&D for a MW-class solid target composed of tungsten was undertaken to produce a pulsed intense neutron source for a future neutron scattering-facility. In order to solve the corrosion of tungsten, tungsten target blocks were clad with tantalum by means of HIP'ing, brazing and electrolytic coating in a molten salt bath. The applicability of the HIP'ing method was tested through fabricating target blocks for KENS (spallation neutron source at KEK). A further investigation to certify the optimum HIP conditions was made with the small punch test method. The results showed that the optimum temperature was 1500 °C at which the W/Ta interface gave the strongest fracture strength. In the case of the block with a hole for thermocouple, it was found that the fabrication preciseness of a straight hole and a tantalum sheath influenced the results. The development of a tungsten stainless-steel alloy was tried to produce a bare tungsten target, using techniques in powder metallurgy. Corrosion tests for various tungsten alloys were made while varying the water temperature and velocity. The mass loss of tungsten in very slow water at 180 °C was as low as 0.022 mg/y, but increased remarkably with water velocity. Simulation experiments for radiation damage to supplement the STIP-III experiments were made to investigate material hardening by hydrogen and helium, and microstructures irradiated by electrons. Both experiments showed consistent results on the order of the dislocation numbers and irradiation hardness among the different tungsten materials. Thermal-hydraulic designs were made for two types of solid target system of tungsten: slab and rod geometry as a function of the proton beam power. The neutronic performance of a solid target system was compared with that of mercury target based on Monte Carlo calculations by using the MCNP code.

A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System.

PubMed

Pompey, Justine M; Foda, Bardees; Singh, Upinder

2015-01-01

Dicer enzymes process double-stranded RNA (dsRNA) into small RNAs that target gene silencing through the RNA interference (RNAi) pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway.

A Single RNaseIII Domain Protein from Entamoeba histolytica Has dsRNA Cleavage Activity and Can Help Mediate RNAi Gene Silencing in a Heterologous System

PubMed Central

Singh, Upinder

2015-01-01

Dicer enzymes process double-stranded RNA (dsRNA) into small RNAs that target gene silencing through the RNA interference (RNAi) pathway. Dicer enzymes are complex, multi-domain RNaseIII proteins, however structural minimalism of this protein has recently emerged in parasitic and fungal systems. The most minimal Dicer, Saccharomyces castellii Dicer1, has a single RNaseIII domain and two double stranded RNA binding domains. In the protozoan parasite Entamoeba histolytica 27nt small RNAs are abundant and mediate silencing, yet no canonical Dicer enzyme has been identified. Although EhRNaseIII does not exhibit robust dsRNA cleavage in vitro, it can process dsRNA in the RNAi-negative background of Saccharomyces cerevisiae, and in conjunction with S. castellii Argonaute1 can partially reconstitute the RNAi pathway. Thus, although EhRNaseIII lacks the domain architecture of canonical or minimal Dicer enzymes, it has dsRNA processing activity that contributes to gene silencing via RNAi. Our data advance the understanding of small RNA biogenesis in Entamoeba as well as broaden the spectrum of non-canonical Dicer enzymes that contribute to the RNAi pathway. PMID:26230096

Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

PubMed

Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

2018-03-15

Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

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2010-12-14

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MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes Multi

Anti-dsDNA Antibodies Bind to Mesangial Annexin II in Lupus Nephritis

PubMed Central

Yung, Susan; Cheung, Kwok Fan; Zhang, Qing

2010-01-01

Production of anti-dsDNA antibodies is a hallmark of lupus nephritis, but how these antibodies deposit in organs and elicit inflammatory damage remains unknown. In this study, we sought to identify antigens on the surface of human mesangial cells (HMC) that mediate the binding of human anti-dsDNA antibodies and the subsequent pathogenic processes. We isolated anti-dsDNA antibodies from patients with lupus nephritis by affinity chromatography. We used multiple methods to identify and characterize antigens from the plasma membrane fraction of mesangial cells that crossreacted with the anti-dsDNA antibodies. We found that annexin II mediated the binding of anti-dsDNA antibodies to HMC. After binding to the mesangial cell surface, anti-dsDNA antibodies were internalized into the cytoplasm and nucleus. This also led to induction of IL-6 secretion and annexin II synthesis, mediated through activation of p38 MAPK, JNK, and AKT. Binding of anti-dsDNA antibodies to annexin II correlated with disease activity in human lupus nephritis. Glomerular expression of annexin II correlated with the severity of nephritis, and annexin II colocalized with IgG and C3 deposits in both human and murine lupus nephritis. Gene silencing of annexin II in HMC reduced binding of anti-dsDNA antibody and partially decreased IL-6 secretion. In summary, our data demonstrate that annexin II mediates the binding of anti-dsDNA antibodies to mesangial cells, contributing to the pathogenesis of lupus nephritis. This interaction provides a potential target for therapeutic intervention. PMID:20847146

Clustered Multi-Task Learning for Automatic Radar Target Recognition

PubMed Central

Li, Cong; Bao, Weimin; Xu, Luping; Zhang, Hua

2017-01-01

Model training is a key technique for radar target recognition. Traditional model training algorithms in the framework of single task leaning ignore the relationships among multiple tasks, which degrades the recognition performance. In this paper, we propose a clustered multi-task learning, which can reveal and share the multi-task relationships for radar target recognition. To further make full use of these relationships, the latent multi-task relationships in the projection space are taken into consideration. Specifically, a constraint term in the projection space is proposed, the main idea of which is that multiple tasks within a close cluster should be close to each other in the projection space. In the proposed method, the cluster structures and multi-task relationships can be autonomously learned and utilized in both of the original and projected space. In view of the nonlinear characteristics of radar targets, the proposed method is extended to a non-linear kernel version and the corresponding non-linear multi-task solving method is proposed. Comprehensive experimental studies on simulated high-resolution range profile dataset and MSTAR SAR public database verify the superiority of the proposed method to some related algorithms. PMID:28953267

Multi-target-qubit unconventional geometric phase gate in a multi-cavity system

NASA Astrophysics Data System (ADS)

Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

2016-02-01

Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

Multi-target-qubit unconventional geometric phase gate in a multi-cavity system.

PubMed

Liu, Tong; Cao, Xiao-Zhi; Su, Qi-Ping; Xiong, Shao-Jie; Yang, Chui-Ping

2016-02-22

Cavity-based large scale quantum information processing (QIP) may involve multiple cavities and require performing various quantum logic operations on qubits distributed in different cavities. Geometric-phase-based quantum computing has drawn much attention recently, which offers advantages against inaccuracies and local fluctuations. In addition, multiqubit gates are particularly appealing and play important roles in QIP. We here present a simple and efficient scheme for realizing a multi-target-qubit unconventional geometric phase gate in a multi-cavity system. This multiqubit phase gate has a common control qubit but different target qubits distributed in different cavities, which can be achieved using a single-step operation. The gate operation time is independent of the number of qubits and only two levels for each qubit are needed. This multiqubit gate is generic, e.g., by performing single-qubit operations, it can be converted into two types of significant multi-target-qubit phase gates useful in QIP. The proposal is quite general, which can be used to accomplish the same task for a general type of qubits such as atoms, NV centers, quantum dots, and superconducting qubits.

Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications.

PubMed

Chadha, Navriti; Silakari, Om

2017-09-01

Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc. The hit molecules were duly synthesized and biochemical estimation of these molecules against aldose reductase (ALR2), protein kinase Cβ (PKCβ) and poly (ADP-ribose) polymerase 1 (PARP-1) led to identification of compound 2 that showed good potency against PARP-1 and ALR2 enzymes. These positive results support the progress of a low cost multi-targeted agent with putative roles in diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

Multi-targeted priming for genome-wide gene expression assays.

PubMed

Adomas, Aleksandra B; Lopez-Giraldez, Francesc; Clark, Travis A; Wang, Zheng; Townsend, Jeffrey P

2010-08-17

Complementary approaches to assaying global gene expression are needed to assess gene expression in regions that are poorly assayed by current methodologies. A key component of nearly all gene expression assays is the reverse transcription of transcribed sequences that has traditionally been performed by priming the poly-A tails on many of the transcribed genes in eukaryotes with oligo-dT, or by priming RNA indiscriminately with random hexamers. We designed an algorithm to find common sequence motifs that were present within most protein-coding genes of Saccharomyces cerevisiae and of Neurospora crassa, but that were not present within their ribosomal RNA or transfer RNA genes. We then experimentally tested whether degenerately priming these motifs with multi-targeted primers improved the accuracy and completeness of transcriptomic assays. We discovered two multi-targeted primers that would prime a preponderance of genes in the genomes of Saccharomyces cerevisiae and Neurospora crassa while avoiding priming ribosomal RNA or transfer RNA. Examining the response of Saccharomyces cerevisiae to nitrogen deficiency and profiling Neurospora crassa early sexual development, we demonstrated that using multi-targeted primers in reverse transcription led to superior performance of microarray profiling and next-generation RNA tag sequencing. Priming with multi-targeted primers in addition to oligo-dT resulted in higher sensitivity, a larger number of well-measured genes and greater power to detect differences in gene expression. Our results provide the most complete and detailed expression profiles of the yeast nitrogen starvation response and N. crassa early sexual development to date. Furthermore, our multi-targeting priming methodology for genome-wide gene expression assays provides selective targeting of multiple sequences and counter-selection against undesirable sequences, facilitating a more complete and precise assay of the transcribed sequences within the genome.

dsRNA-protein interactions studied by molecular dynamics techniques. Unravelling dsRNA recognition by DCL1.

PubMed

Drusin, Salvador I; Suarez, Irina P; Gauto, Diego F; Rasia, Rodolfo M; Moreno, Diego M

2016-04-15

Double stranded RNA (dsRNA) participates in several biological processes, where RNA molecules acquire secondary structure inside the cell through base complementarity. The double stranded RNA binding domain (dsRBD) is one of the main protein folds that is able to recognize and bind to dsRNA regions. The N-terminal dsRBD of DCL1 in Arabidopsis thaliana (DCL1-1), in contrast to other studied dsRBDs, lacks a stable structure, behaving as an intrinsically disordered protein. DCL1-1 does however recognize dsRNA by acquiring a canonical fold in the presence of its substrate. Here we present a detailed modeling and molecular dynamics study of dsRNA recognition by DCL1-1. We found that DCL1-1 forms stable complexes with different RNAs and we characterized the residues involved in binding. Although the domain shows a binding loop substantially shorter than other homologs, it can still interact with the dsRNA and results in bending of the dsRNA A-type helix. Furthermore, we found that R8, a non-conserved residue located in the first dsRNA binding region, recognizes preferentially mismatched base pairs. We discuss our findings in the context of the function of DCL1-1 within the microRNA processing complex. Copyright © 2016 Elsevier Inc. All rights reserved.

Fusion-based multi-target tracking and localization for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2008-04-01

In this paper, we have presented two approaches addressing visual target tracking and localization in complex urban environment. The two techniques presented in this paper are: fusion-based multi-target visual tracking, and multi-target localization via camera calibration. For multi-target tracking, the data fusion concepts of hypothesis generation/evaluation/selection, target-to-target registration, and association are employed. An association matrix is implemented using RGB histograms for associated tracking of multi-targets of interests. Motion segmentation of targets of interest (TOI) from the background was achieved by a Gaussian Mixture Model. Foreground segmentation, on other hand, was achieved by the Connected Components Analysis (CCA) technique. The tracking of individual targets was estimated by fusing two sources of information, the centroid with the spatial gating, and the RGB histogram association matrix. The localization problem is addressed through an effective camera calibration technique using edge modeling for grid mapping (EMGM). A two-stage image pixel to world coordinates mapping technique is introduced that performs coarse and fine location estimation of moving TOIs. In coarse estimation, an approximate neighborhood of the target position is estimated based on nearest 4-neighbor method, and in fine estimation, we use Euclidean interpolation to localize the position within the estimated four neighbors. Both techniques were tested and shown reliable results for tracking and localization of Targets of interests in complex urban environment.

DsJ(2860) as the First Radial Excitation of Ds0*(2317)

NASA Astrophysics Data System (ADS)

van Beveren, Eef; Rupp, George

2006-11-01

A coupled-channel model previously employed to describe the narrow Ds0*(2317) and broad D0*(2400) charmed scalar mesons is generalized so as to include all ground-state pseudoscalar-pseudoscalar and vector-vector two-meson channels. All parameters are chosen fixed at published values, except for the overall coupling constant, which is fine-tuned to reproduce the Ds0*(2317) mass. Thus, the radial excitations Ds0*(2850) and D0*(2740) are predicted, both with a width of about 50 MeV. The former state appears to correspond to the new DsJ(2860) resonance decaying to DK announced by BABAR in the course of this work. Also, the D0*(2400) resonance is roughly reproduced, though perhaps with a somewhat too low central resonance peak.

Knockdown of Midgut Genes by dsRNA-Transgenic Plant-Mediated RNA Interference in the Hemipteran Insect Nilaparvata lugens

PubMed Central

Zha, Wenjun; Peng, Xinxin; Chen, Rongzhi; Du, Bo; Zhu, Lili; He, Guangcun

2011-01-01

Background RNA interference (RNAi) is a powerful technique for functional genomics research in insects. Transgenic plants producing double-stranded RNA (dsRNA) directed against insect genes have been reported for lepidopteran and coleopteran insects, showing potential for field-level control of insect pests, but this has not been reported for other insect orders. Methodology/Principal Findings The Hemipteran insect brown planthopper (Nilaparvata lugens Stål) is a typical phloem sap feeder specific to rice (Oryza sativa L.). To analyze the potential of exploiting RNAi-mediated effects in this insect, we identified genes (Nlsid-1 and Nlaub) encoding proteins that might be involved in the RNAi pathway in N. lugens. Both genes are expressed ubiquitously in nymphs and adult insects. Three genes (the hexose transporter gene NlHT1, the carboxypeptidase gene Nlcar and the trypsin-like serine protease gene Nltry) that are highly expressed in the N. lugens midgut were isolated and used to develop dsRNA constructs for transforming rice. RNA blot analysis showed that the dsRNAs were transcribed and some of them were processed to siRNAs in the transgenic lines. When nymphs were fed on rice plants expressing dsRNA, levels of transcripts of the targeted genes in the midgut were reduced; however, lethal phenotypic effects after dsRNA feeding were not observed. Conclusions Our study shows that genes for the RNAi pathway (Nlsid-1 and Nlaub) are present in N. lugens. When insects were fed on rice plant materials expressing dsRNAs, RNA interference was triggered and the target genes transcript levels were suppressed. The gene knockdown technique described here may prove to be a valuable tool for further investigations in N. lugens. The results demonstrate the potential of dsRNA-mediated RNAi for field-level control of planthoppers, but appropriate target genes must be selected when designing the dsRNA-transgenic plants. PMID:21655219

Collaborative identification method for sea battlefield target based on deep convolutional neural networks

NASA Astrophysics Data System (ADS)

Zheng, Guangdi; Pan, Mingbo; Liu, Wei; Wu, Xuetong

2018-03-01

The target identification of the sea battlefield is the prerequisite for the judgment of the enemy in the modern naval battle. In this paper, a collaborative identification method based on convolution neural network is proposed to identify the typical targets of sea battlefields. Different from the traditional single-input/single-output identification method, the proposed method constructs a multi-input/single-output co-identification architecture based on optimized convolution neural network and weighted D-S evidence theory. The simulation results show that

DS-8201a, a new HER2-targeting antibody-drug conjugate incorporating a novel DNA topoisomerase I inhibitor, overcomes HER2-positive gastric cancer T-DM1 resistance.

PubMed

Takegawa, Naoki; Nonagase, Yoshikane; Yonesaka, Kimio; Sakai, Kazuko; Maenishi, Osamu; Ogitani, Yusuke; Tamura, Takao; Nishio, Kazuto; Nakagawa, Kazuhiko; Tsurutani, Junji

2017-10-15

Anti-HER2 therapies are beneficial for patients with HER2-positive breast or gastric cancer. T-DM1 is a HER2-targeting antibody-drug conjugate (ADC) comprising the antibody trastuzumab, a linker, and the tubulin inhibitor DM1. Although effective in treating advanced breast cancer, all patients eventually develop T-DM1 resistance. DS-8201a is a new ADC incorporating an anti-HER2 antibody, a newly developed, enzymatically cleavable peptide linker, and a novel, potent, exatecan-derivative topoisomerase I inhibitor (DXd). DS-8201a has a drug-to-antibody-ratio (DAR) of 8, which is higher than that of T-DM1 (3.5). Owing to these unique characteristics and unlike T-DM1, DS-8201a is effective against cancers with low-HER2 expression. In the present work, T-DM1-resistant cells (N87-TDMR), established using the HER2-positive gastric cancer line NCI-N87 and continuous T-DM1 exposure, were shown to be susceptible to DS-8201a. The ATP-binding cassette (ABC) transporters ABCC2 and ABCG2 were upregulated in N87-TDMR cells, but HER2 overexpression was retained. Furthermore, inhibition of ABCC2 and ABCG2 by MK571 restored T-DM1 sensitivity. Therefore, resistance to T-DM1 is caused by efflux of its payload DM1, due to aberrant expression of ABC transporters. In contrast to DM1, DXd payload of DS-8201a inhibited the growth of N87-TDMR cells in vitro. This suggests that either DXd may be a poor substrate of ABCC2 and ABCG2 in comparison to DM1, or the high DAR of DS-8201a relative to T-DM1 compensates for increased efflux. Notably, N87-TDMR xenograft tumor growth was prevented by DS-8201a. In conclusion, the efficacy of DS-8201a as a treatment for patients with T-DM1-resistant breast or gastric cancer merits investigation. © 2017 UICC.

Method of quantitating dsDNA

DOEpatents

Stark, Peter C.; Kuske, Cheryl R.; Mullen, Kenneth I.

2002-01-01

A method for quantitating dsDNA in an aqueous sample solution containing an unknown amount of dsDNA. A first aqueous test solution containing a known amount of a fluorescent dye-dsDNA complex and at least one fluorescence-attenutating contaminant is prepared. The fluorescence intensity of the test solution is measured. The first test solution is diluted by a known amount to provide a second test solution having a known concentration of dsDNA. The fluorescence intensity of the second test solution is measured. Additional diluted test solutions are similarly prepared until a sufficiently dilute test solution having a known amount of dsDNA is prepared that has a fluorescence intensity that is not attenuated upon further dilution. The value of the maximum absorbance of this solution between 200-900 nanometers (nm), referred to herein as the threshold absorbance, is measured. A sample solution having an unknown amount of dsDNA and an absorbance identical to that of the sufficiently dilute test solution at the same chosen wavelength is prepared. Dye is then added to the sample solution to form the fluorescent dye-dsDNA-complex, after which the fluorescence intensity of the sample solution is measured and the quantity of dsDNA in the sample solution is determined. Once the threshold absorbance of a sample solution obtained from a particular environment has been determined, any similarly prepared sample solution taken from a similar environment and having the same value for the threshold absorbance can be quantified for dsDNA by adding a large excess of dye to the sample solution and measuring its fluorescence intensity.

Multi-Agent Cooperative Target Search

PubMed Central

Hu, Jinwen; Xie, Lihua; Xu, Jun; Xu, Zhao

2014-01-01

This paper addresses a vision-based cooperative search for multiple mobile ground targets by a group of unmanned aerial vehicles (UAVs) with limited sensing and communication capabilities. The airborne camera on each UAV has a limited field of view and its target discriminability varies as a function of altitude. First, by dividing the whole surveillance region into cells, a probability map can be formed for each UAV indicating the probability of target existence within each cell. Then, we propose a distributed probability map updating model which includes the fusion of measurement information, information sharing among neighboring agents, information decay and transmission due to environmental changes such as the target movement. Furthermore, we formulate the target search problem as a multi-agent cooperative coverage control problem by optimizing the collective coverage area and the detection performance. The proposed map updating model and the cooperative control scheme are distributed, i.e., assuming that each agent only communicates with its neighbors within its communication range. Finally, the effectiveness of the proposed algorithms is illustrated by simulation. PMID:24865884

Dietary risk assessment of v-ATPase A dsRNAs on monarch butterfly larvae

USDA-ARS?s Scientific Manuscript database

The goal of this study is to assess the risks of RNA interference (RNAi)-based genetically engineered crops on a non-target arthropod, monarch butterfly, Danaus plexippus. We hypothesize that an insecticidal double-stranded (ds) RNA targeting western corn rootworm, Diabrotica virgifera virgifera, ha...

Extending multi-tenant architectures: a database model for a multi-target support in SaaS applications

NASA Astrophysics Data System (ADS)

Rico, Antonio; Noguera, Manuel; Garrido, José Luis; Benghazi, Kawtar; Barjis, Joseph

2016-05-01

Multi-tenant architectures (MTAs) are considered a cornerstone in the success of Software as a Service as a new application distribution formula. Multi-tenancy allows multiple customers (i.e. tenants) to be consolidated into the same operational system. This way, tenants run and share the same application instance as well as costs, which are significantly reduced. Functional needs vary from one tenant to another; either companies from different sectors run different types of applications or, although deploying the same functionality, they do differ in the extent of their complexity. In any case, MTA leaves one major concern regarding the companies' data, their privacy and security, which requires special attention to the data layer. In this article, we propose an extended data model that enhances traditional MTAs in respect of this concern. This extension - called multi-target - allows MT applications to host, manage and serve multiple functionalities within the same multi-tenant (MT) environment. The practical deployment of this approach will allow SaaS vendors to target multiple markets or address different levels of functional complexity and yet commercialise just one single MT application. The applicability of the approach is demonstrated via a case study of a real multi-tenancy multi-target (MT2) implementation, called Globalgest.

Structure of RDE-4 dsRBDs and mutational studies provide insights into dsRNA recognition in the Caenorhabditis elegans RNAi pathway.

PubMed

Chiliveri, Sai Chaitanya; Deshmukh, Mandar V

2014-02-15

The association of RDE-4 (RNAi defective 4), a protein containing two dsRBDs (dsRNA-binding domains), with long dsRNA and Dcr-1 (Dicer1 homologue) initiates the siRNA pathway in Caenorhabditis elegans. Unlike its homologues in higher eukaryotes, RDE-4 dsRBDs possess weak (micromolar) affinity for short dsRNA. With increasing length of dsRNA, RDE-4 exhibits enhanced affinity due to co-operativity. The linker and dsRBD2 are indispensable for RDE-4's simultaneous interaction with dsRNA and Dcr-1. In the present study, we have determined the solution structures of RDE-4 constructs that contain both dsRBDs and the linker region. In addition to the canonical dsRBD fold, both dsRBDs of RDE-4 show modified structural features such as truncation in the β1-β2 loop that rationalize RDE-4's relatively weak dsRNA affinity. Structure and binding studies demonstrate that dsRBD2 plays a decisive role in the RDE-4-dsRNA interaction; however, in contrast with previous findings, we found ephemeral interaction of RDE-4 dsRBD1 with dsRNA. More importantly, mutations in two tandem lysine residues (Lys217 and Lys218) in dsRBD2 impair RDE-4's dsRNA-binding ability and could obliterate RNAi initiation in C. elegans. Additionally, we postulate a structural basis for the minimal requirement of linker and dsRBD2 for RDE-4's association with dsRNA and Dcr-1.

Discriminating styles (DS) and pollen-mediated pseudo-self-compatibility (PMPSC) in Nemesia strumosa Benth. : Part 1: Characteristics and inheritance of DS.

PubMed

Robacker, C D; Ascher, P D

1981-09-01

Nemesia strumosa plants were discovered which had styles capable of discriminating among incompatible pollen tubes from different pollinators, allowing growth of some but not others. All but 3 of 26 families tested had at least some members with discriminating styles (DS). Presence and level of DS was independent of S genotype. Plants with pseudo-self-compatiblity (PSC) levels greater than 10% had the trait, though many plants with strong DS had PSC levels less than 10%. Self pollination of highly DS plants produced mostly DS offspring, but of differing sensitivities. Some progenies from crosses between a family of highly DS plants and unrelated, probably low DS plants segregated half DS and half non-DS, while others consisted of mostly DS or mostly non-DS. The DS phenomenon is probably caused by PSC genes.

Composite Structural Analysis of Flat-Back Shaped Blade for Multi-MW Class Wind Turbine

NASA Astrophysics Data System (ADS)

Kim, Soo-Hyun; Bang, Hyung-Joon; Shin, Hyung-Ki; Jang, Moon-Seok

2014-06-01

This paper provides an overview of failure mode estimation based on 3D structural finite element (FE) analysis of the flat-back shaped wind turbine blade. Buckling stability, fiber failure (FF), and inter-fiber failure (IFF) analyses were performed to account for delamination or matrix failure of composite materials and to predict the realistic behavior of the entire blade region. Puck's fracture criteria were used for IFF evaluation. Blade design loads applicable to multi-megawatt (MW) wind turbine systems were calculated according to the Germanischer Lloyd (GL) guideline and the International Electrotechnical Commission (IEC) 61400-1 standard, under Class IIA wind conditions. After the post-processing of final load results, a number of principal load cases were selected and converted into applied forces at the each section along the blade's radius of the FE model. Nonlinear static analyses were performed for laminate failure, FF, and IFF check. For buckling stability, linear eigenvalue analysis was performed. As a result, we were able to estimate the failure mode and locate the major weak point.

Oral delivery of dsRNA by microbes: Beyond pest control.

PubMed

Abrieux, Antoine; Chiu, Joanna C

2016-01-01

RNA interference (RNAi) by oral delivery of dsRNA in insects has great potential as a tool for integrated pest management (IPM), especially with respect to addressing the need to reduce off-target effect and slow down resistance development to chemical insecticides. Employing the natural association existing between insect and yeast, we developed a novel method to enable the knock down of vital genes in the pest insect Drosophila suzukii through oral delivery of species-specific dsRNA using genetically modified Saccharomyces cerevisae. D. suzukii that were fed with our "yeast biopesticide" showed a significant decrease in fitness. In this perspective article, we postulate that this approach could be adapted to a large number of species, given the great diversity of symbiotic interactions involving microorganisms and host species. Furthermore, we speculate that beyond its application as biopesticide, dsRNA delivery by genetically modified microbes can also serve to facilitate reverse genetic applications, specifically in non-model organisms.

Multi-Target State Extraction for the SMC-PHD Filter

PubMed Central

Si, Weijian; Wang, Liwei; Qu, Zhiyu

2016-01-01

The sequential Monte Carlo probability hypothesis density (SMC-PHD) filter has been demonstrated to be a favorable method for multi-target tracking. However, the time-varying target states need to be extracted from the particle approximation of the posterior PHD, which is difficult to implement due to the unknown relations between the large amount of particles and the PHD peaks representing potential target locations. To address this problem, a novel multi-target state extraction algorithm is proposed in this paper. By exploiting the information of measurements and particle likelihoods in the filtering stage, we propose a validation mechanism which aims at selecting effective measurements and particles corresponding to detected targets. Subsequently, the state estimates of the detected and undetected targets are performed separately: the former are obtained from the particle clusters directed by effective measurements, while the latter are obtained from the particles corresponding to undetected targets via clustering method. Simulation results demonstrate that the proposed method yields better estimation accuracy and reliability compared to existing methods. PMID:27322274

75 FR 25911 - 30-Day Notice of Proposed Information Collection: Forms DS-2053, DS-2054; Medical Examination for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... DEPARTMENT OF STATE [Public Notice 6995] 30-Day Notice of Proposed Information Collection: Forms DS-2053, DS-2054; Medical Examination for Immigrant or Refugee Applicant; DS- 3030, Chest X-Ray and..., Medical Examination for Immigrant or Refugee Applicant (2007 Technical Instructions); and DS-3030, Chest X...

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

Computational sequence analysis of predicted long dsRNA transcriptomes of major crops reveals sequence complementarity with human genes.

PubMed

Jensen, Peter D; Zhang, Yuanji; Wiggins, B Elizabeth; Petrick, Jay S; Zhu, Jin; Kerstetter, Randall A; Heck, Gregory R; Ivashuta, Sergey I

2013-01-01

Long double-stranded RNAs (long dsRNAs) are precursors for the effector molecules of sequence-specific RNA-based gene silencing in eukaryotes. Plant cells can contain numerous endogenous long dsRNAs. This study demonstrates that such endogenous long dsRNAs in plants have sequence complementarity to human genes. Many of these complementary long dsRNAs have perfect sequence complementarity of at least 21 nucleotides to human genes; enough complementarity to potentially trigger gene silencing in targeted human cells if delivered in functional form. However, the number and diversity of long dsRNA molecules in plant tissue from crops such as lettuce, tomato, corn, soy and rice with complementarity to human genes that have a long history of safe consumption supports a conclusion that long dsRNAs do not present a significant dietary risk.

Nuclear factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA.

PubMed

Jayachandran, Uma; Grey, Heather; Cook, Atlanta G

2016-02-29

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3' untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

PubMed Central

Sun, Baoliang; Jiang, Chunlan; Li, Ming

2016-01-01

An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

First observation of the decay Ds+-->pn.

PubMed

Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; Lopez, A; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Naik, P; Rademacker, J; Asner, D M; Edwards, K W; Reed, J; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Hunt, J M; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Ledoux, J; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T

2008-05-09

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

Double-shell target fabrication workshop-2016 report

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

Wang, Y. Morris; Oertel, John; Farrell, Michael

On June 30, 2016, over 40 representatives from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), General Atomics (GA), Laboratory for Laser Energetics (LLE), Schafer Corporation, and NNSA headquarter attended a double-shell (DS) target fabrication workshop at Livermore, California. Pushered-single-shell (PSS) and DS metalgas platforms potentially have a large impact on programmatic applications. The goal of this focused workshop is to bring together target fabrication scientists, physicists, and designers to brainstorm future PSS and DS target fabrication needs and strategies. This one-day workshop intends to give an overall view of historical information, recent approaches, and future research activitiesmore » at each participating organization. Five topical areas have been discussed that are vital to the success of future DS target fabrications, including inner metal shells, foam spheres, outer ablators, fill tube assembly, and metrology.« less

Measurement of the absolute branching fraction of Ds0 *(2317 )±→π0Ds±

NASA Astrophysics Data System (ADS)

Ablikim, M.; Achasov, M. N.; Ahmed, S.; Albrecht, M.; Amoroso, A.; An, F. F.; An, Q.; Bai, J. Z.; Bai, Y.; Bakina, O.; Baldini Ferroli, R.; Ban, Y.; Bennett, D. W.; Bennett, J. V.; Berger, N.; Bertani, M.; Bettoni, D.; Bian, J. M.; Bianchi, F.; Boger, E.; Boyko, I.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chai, J.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, P. L.; Chen, S. J.; Chen, X. R.; Chen, Y. B.; Chu, X. K.; Cibinetto, G.; Dai, H. L.; Dai, J. P.; Dbeyssi, A.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; de Mori, F.; Ding, Y.; Dong, C.; Dong, J.; Dong, L. Y.; Dong, M. Y.; Dou, Z. L.; Du, S. X.; Duan, P. F.; Fang, J.; Fang, S. S.; Fang, X.; Fang, Y.; Farinelli, R.; Fava, L.; Fegan, S.; Feldbauer, F.; Felici, G.; Feng, C. Q.; Fioravanti, E.; Fritsch, M.; Fu, C. D.; Gao, Q.; Gao, X. L.; Gao, Y.; Gao, Y. G.; Gao, Z.; Garzia, I.; Goetzen, K.; Gong, L.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, S.; Gu, Y. T.; Guo, A. Q.; Guo, L. B.; Guo, R. P.; Guo, Y. P.; Haddadi, Z.; Han, S.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, X. Q.; Heinsius, F. H.; Held, T.; Heng, Y. K.; Holtmann, T.; Hou, Z. L.; Hu, C.; Hu, H. M.; Hu, T.; Hu, Y.; Huang, G. S.; Huang, J. S.; Huang, X. T.; Huang, X. Z.; Huang, Z. L.; Hussain, T.; Ikegami Andersson, W.; Ji, Q.; Ji, Q. P.; Ji, X. B.; Ji, X. L.; Jiang, X. S.; Jiang, X. Y.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jin, Y.; Johansson, T.; Julin, A.; Kalantar-Nayestanaki, N.; Kang, X. L.; Kang, X. S.; Kavatsyuk, M.; Ke, B. C.; Khan, T.; Khoukaz, A.; Kiese, P.; Kliemt, R.; Koch, L.; Kolcu, O. B.; Kopf, B.; Kornicer, M.; Kuemmel, M.; Kuessner, M.; Kuhlmann, M.; Kupsc, A.; Kühn, W.; Lange, J. S.; Lara, M.; Larin, P.; Lavezzi, L.; Leiber, S.; Leithoff, H.; Leng, C.; Li, C.; Li, Cheng; Li, D. M.; Li, F.; Li, F. Y.; Li, G.; Li, H. B.; Li, H. J.; Li, J. C.; Li, J. Q.; Li, K. J.; Li, Kang; Li, Ke; Li, Lei; Li, P. L.; Li, P. R.; Li, Q. Y.; Li, T.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Lin, D. X.; Liu, B.; Liu, B. J.; Liu, C. X.; Liu, D.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H. B.; Liu, H. M.; Liu, Huanhuan; Liu, Huihui; Liu, J. B.; Liu, J. P.; Liu, J. Y.; Liu, K.; Liu, K. Y.; Liu, Ke; Liu, L. D.; Liu, P. L.; Liu, Q.; Liu, S. B.; Liu, X.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqing; Long, Y. F.; Lou, X. C.; Lu, H. J.; Lu, J. G.; Lu, Y.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, X. L.; Lyu, X. R.; Ma, F. C.; Ma, H. L.; Ma, L. L.; Ma, M. M.; Ma, Q. M.; Ma, T.; Ma, X. N.; Ma, X. Y.; Ma, Y. M.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, Y. J.; Mao, Z. P.; Marcello, S.; Meng, Z. X.; Messchendorp, J. G.; Mezzadri, G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Mo, Y. J.; Morales Morales, C.; Morello, G.; Muchnoi, N. Yu.; Muramatsu, H.; Musiol, P.; Mustafa, A.; Nefedov, Y.; Nerling, F.; Nikolaev, I. B.; Ning, Z.; Nisar, S.; Niu, S. L.; Niu, X. Y.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Pan, Y.; Papenbrock, M.; Patteri, P.; Pelizaeus, M.; Pellegrino, J.; Peng, H. P.; Peters, K.; Pettersson, J.; Ping, J. L.; Ping, R. G.; Pitka, A.; Poling, R.; Prasad, V.; Qi, H. R.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, N.; Qin, X. S.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Redmer, C. F.; Richter, M.; Ripka, M.; Rolo, M.; Rong, G.; Rosner, Ch.; Ruan, X. D.; Sarantsev, A.; Savrié, M.; Schnier, C.; Schoenning, K.; Shan, W.; Shao, M.; Shen, C. P.; Shen, P. X.; Shen, X. Y.; Sheng, H. Y.; Song, J. J.; Song, W. M.; Song, X. Y.; Sosio, S.; Sowa, C.; Spataro, S.; Sun, G. X.; Sun, J. F.; Sun, L.; Sun, S. S.; Sun, X. H.; Sun, Y. J.; Sun, Y. K.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, G. Y.; Tang, X.; Tapan, I.; Tiemens, M.; Tsednee, B.; Uman, I.; Varner, G. S.; Wang, B.; Wang, B. L.; Wang, D.; Wang, D. Y.; Wang, Dan; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, Meng; Wang, P.; Wang, P. L.; Wang, W. P.; Wang, X. F.; Wang, Y.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. H.; Wang, Z. Y.; Wang, Zongyuan; Weber, T.; Wei, D. H.; Weidenkaff, P.; Wen, S. P.; Wiedner, U.; Wolke, M.; Wu, L. H.; Wu, L. J.; Wu, Z.; Xia, L.; Xia, X.; Xia, Y.; Xiao, D.; Xiao, H.; Xiao, Y. J.; Xiao, Z. J.; Xie, Y. G.; Xie, Y. H.; Xiong, X. A.; Xiu, Q. L.; Xu, G. F.; Xu, J. J.; Xu, L.; Xu, Q. J.; Xu, Q. N.; Xu, X. P.; Yan, L.; Yan, W. B.; Yan, W. C.; Yan, W. C.; Yan, Y. H.; Yang, H. J.; Yang, H. X.; Yang, L.; Yang, Y. H.; Yang, Y. X.; Yang, Yifan; Ye, M.; Ye, M. H.; Yin, J. H.; You, Z. Y.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yuan, C. Z.; Yuan, Y.; Yuncu, A.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zeng, Z.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. L.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, K.; Zhang, L.; Zhang, S. Q.; Zhang, X. Y.; Zhang, Y. H.; Zhang, Y. T.; Zhang, Yang; Zhang, Yao; Zhang, Yu; Zhang, Z. H.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, J. W.; Zhao, J. Y.; Zhao, J. Z.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, W. J.; Zheng, Y. H.; Zhong, B.; Zhou, L.; Zhou, X.; Zhou, X. K.; Zhou, X. R.; Zhou, X. Y.; Zhou, Y. X.; Zhu, J.; Zhu, J.; Zhu, K.; Zhu, K. J.; Zhu, S.; Zhu, S. H.; Zhu, X. L.; Zhu, Y. C.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Besiii Collaboration

2018-03-01

The process e+e-→Ds*+Ds0 *(2317 )-+c .c . is observed for the first time with the data sample of 567 pb-1 collected with the BESIII detector operating at the BEPCII collider at a center-of-mass energy √{s }=4.6 GeV . The statistical significance of the Ds0 *(2317 )± signal is 5.8 σ and the mass is measured to be (2318.3 ±1.2 ±1.2 ) MeV /c2 . The absolute branching fraction B (Ds0 *(2317 )±→π0Ds±) is measured as 1.00-0.14+0.00(stat)-0.14+0.00(syst) for the first time. The uncertainties are statistical and systematic, respectively.

Self-assembling HA/PEI/dsRNA-p21 ternary complexes for CD44 mediated small active RNA delivery to colorectal cancer.

PubMed

Feng, Chen-Lin; Han, Yan-Xing; Guo, Hui-Hui; Ma, Xiao-Lei; Wang, Zhi-Qiang; Wang, Lu-Lu; Zheng, Wen-Sheng; Jiang, Jian-Dong

2017-11-01

Our previous work proved that sequence specific double strand RNA (dsRNA-p21) effectively activated p21 gene expression of colorectal cancer (CRC) cells and consequently suppressed CRC growth. However, efficient delivery system is a significant challenge to achieve sufficient therapy. In this study, a self-assembled HA/PEI/dsRNA-p21 ternary complex (TC-dsRNA-p21) was developed for the tumor-target delivery of dsRNA-p21 into CRC cells. Hyaluronic acid (HA) was introduced to shield the PEI/dsRNA-p21 binary complexes (BC-dsRNA-p21) for reducing the cytotoxicity of PEI and for increasing the tumor-targeted intracellular uptake by cancer cells through HA-CD44 mediated endocytosis. Comparing to the BC-dsRNA-p21, the TC-dsRNA-p21 showed increase in size, decrease in zeta potential, low cytotoxicity as well as high stability in physiological conditions due to the anionic shielding. Confocal microscopy analysis and flow cytometry confirmed that TC-dsRNA-p21 had high transfection efficiency in the CD44-abundant Lovo cells, as compared with binary complex. In vitro physiological experiment showed that, comparing to the control group, the TC-dsRNA-p21 effectively activated the expression of p21 mRNA and P21 protein, causing blockage of cell cycle at G 0 /G 1 phase and suppression of cancer cell proliferation as well as colony formation. Furthermore, in vivo distribution experiment demonstrated that the TC-dsRNA-p21 could effectively accumulate at rectal wall for up to 10 h, following in situ application. These findings indicated that TC-dsRNA-p21 might hold great potential for delivering dsRNA-p21 to treat CRC.

Noise-induced creation and annihilation of dissipative solitons (DS) in a passively mode-locked laser

NASA Astrophysics Data System (ADS)

Teamir, Tesfay; Elahi, Parviz; Makey, Ghaith; Fatih, Ilday

Passive mode-locking, resulting in self-organized formation of femtoseconds-long laser pulses, constitutes a far-from-equilibrium steady state. Mode-locking is not only important for laser technology, but also of fundamental interest for broad class of systems. Despite numerous studies on their nonlinear dynamics, there is little understanding of the transitions that intrinsic noise can induce. We show that transitions between single-DS and multi-DS states can be triggered. Near critical points, DS states are observed to repeatedly exchange energy among themselves, form DS clusters with varying or vibrating temporal separation, often followed by random transformations among different states. This critical behavior appears to be caused by soliton-soliton or soliton-generated dispersive wave interactions. Irrespective of the specifics of the state, the measured noise level of the laser starts at a moderate value, is then reduced, as the DS's energy is increased. Further increases in power (nonlinearity) drives it towards a noisy critical state, where creation or annihilation of pulses occurs just before a new steady state is formed. These noise-induced transitions between steady states can shed light on the thermodynamics of far-from-equilibrium systems. TàBITAK (113F319) and ERC CoG (617521).

Suppressed Decays of Ds+ Mesons to Two Pseudoscalar Mesons

NASA Astrophysics Data System (ADS)

Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Menaa, N.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sia, R.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Adam, N. E.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Ernst, J.; Ecklund, K. M.; Severini, H.; Love, W.; Savinov, V.; Lopez, A.; Mehrabyan, S.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.

2007-11-01

Using data collected near the Ds*+Ds- peak production energy Ecm=4170MeV by the CLEO-c detector, we study the decays of Ds+ mesons to two pseudoscalar mesons. We report on searches for the singly Cabibbo-suppressed Ds+ decay modes K+η, K+η', π+KS0, K+π0, and the isospin-forbidden decay mode Ds+→π+π0. We normalize with respect to the Cabibbo-favored Ds+ modes π+η, π+η', and K+KS0, and obtain ratios of branching fractions: B(Ds+→K+η)/B(Ds+→π+η)=(8.9±1.5±0.4)%, B(Ds+→K+η')/B(Ds+→π+η')=(4.2±1.3±0.3)%, B(Ds+→π+KS0)/B(Ds+→K+KS0)=(8.2±0.9±0.2)%, B(Ds+→K+π0)/B(Ds+→K+KS0)=(5.5±1.3±0.7)%, and B(Ds+→π+π0)/B(Ds+→K+KS0)<4.1% at 90% C.L., where the uncertainties are statistical and systematic, respectively.

Improvement of pest resistance in transgenic tobacco plants expressing dsRNA of an insect-associated gene EcR.

PubMed

Zhu, Jin-Qi; Liu, Shumin; Ma, Yao; Zhang, Jia-Qi; Qi, Hai-Sheng; Wei, Zhao-Jun; Yao, Qiong; Zhang, Wen-Qing; Li, Sheng

2012-01-01

The adoption of pest-resistant transgenic plants to reduce yield loss and pesticide utilization has been successful in the past three decades. Recently, transgenic plant expressing double-stranded RNA (dsRNA) targeting pest genes emerges as a promising strategy for improving pest resistance in crops. The steroid hormone, 20-hydroxyecdysone (20E), predominately controls insect molting via its nuclear receptor complex, EcR-USP. Here we report that pest resistance is improved in transgenic tobacco plants expressing dsRNA of EcR from the cotton bollworm, Helicoverpa armigera, a serious lepidopteran pest for a variety of crops. When H. armigera larvae were fed with the whole transgenic tobacco plants expressing EcR dsRNA, resistance to H. armigera was significantly improved in transgenic plants. Meanwhile, when H. armigera larvae were fed with leaves of transgenic tobacco plants expressing EcR dsRNA, its EcR mRNA level was dramatically decreased causing molting defects and larval lethality. In addition, the transgenic tobacco plants expressing H. armigera EcR dsRNA were also resistant to another lepidopteran pest, the beet armyworm, Spodoptera exigua, due to the high similarity in the nucleotide sequences of their EcR genes. This study provides additional evidence that transgenic plant expressing dsRNA targeting insect-associated genes is able to improve pest resistance.

Two-phase framework for near-optimal multi-target Lambert rendezvous

NASA Astrophysics Data System (ADS)

Bang, Jun; Ahn, Jaemyung

2018-03-01

This paper proposes a two-phase framework to obtain a near-optimal solution of multi-target Lambert rendezvous problem. The objective of the problem is to determine the minimum-cost rendezvous sequence and trajectories to visit a given set of targets within a maximum mission duration. The first phase solves a series of single-target rendezvous problems for all departure-arrival object pairs to generate the elementary solutions, which provides candidate rendezvous trajectories. The second phase formulates a variant of traveling salesman problem (TSP) using the elementary solutions prepared in the first phase and determines the final rendezvous sequence and trajectories of the multi-target rendezvous problem. The validity of the proposed optimization framework is demonstrated through an asteroid exploration case study.

Multi-dimensional distribution of near-field ionospheric disturbances produced by the 2015 Mw7.8 Nepal earthquake

NASA Astrophysics Data System (ADS)

Tang, Jun; Yuan, Yunbin

2017-10-01

Ionospheric anomalies possibly associated with large earthquakes, particularly coseismic ionospheric disturbances, have been detected by global positioning system (GPS). A large Nepal earthquake with magnitude Mw7.8 occurred on April 25, 2015. In this paper, we investigate the multi-dimensional distribution of near-field coseismic ionospheric disturbances (CIDs) using total electron content (TEC) and computerized ionospheric tomography (CIT) from regional GPS observational data. The results show significant ionospheric TEC disturbances and interesting multi-dimensional structures around the main shock. Regarding the TEC changes, coseismic ionospheric disturbances occur approximately 10-20 min after the earthquake northeast and northwest of epicentre. The maximum ridge-to-trough amplitude of CIDs is up to approximately 0.90 TECU/min. Propagation velocities of the TEC disturbances are 1.27 ± 0.06 km/s and 1.91 ± 0.38 km/s. It is believed that the ionospheric disturbances are triggered by acoustic and Rayleigh waves. Tomographic results show that the three-dimensional distribution of ionospheric disturbances obviously increases at an altitude of 300 km above the surrounding epicentre, predominantly in the entire region between 200 km and 400 km. Significant ionospheric disturbances appear at 06:30 UT from tomographic images. This study reveals characteristics of an ionospheric anomaly caused by the Nepal earthquake.

An Automatic Multi-Target Independent Analysis Framework for Non-Planar Infrared-Visible Registration.

PubMed

Sun, Xinglong; Xu, Tingfa; Zhang, Jizhou; Zhao, Zishu; Li, Yuankun

2017-07-26

In this paper, we propose a novel automatic multi-target registration framework for non-planar infrared-visible videos. Previous approaches usually analyzed multiple targets together and then estimated a global homography for the whole scene, however, these cannot achieve precise multi-target registration when the scenes are non-planar. Our framework is devoted to solving the problem using feature matching and multi-target tracking. The key idea is to analyze and register each target independently. We present a fast and robust feature matching strategy, where only the features on the corresponding foreground pairs are matched. Besides, new reservoirs based on the Gaussian criterion are created for all targets, and a multi-target tracking method is adopted to determine the relationships between the reservoirs and foreground blobs. With the matches in the corresponding reservoir, the homography of each target is computed according to its moving state. We tested our framework on both public near-planar and non-planar datasets. The results demonstrate that the proposed framework outperforms the state-of-the-art global registration method and the manual global registration matrix in all tested datasets.

SW-MW infrared spectrometer for lunar mission

NASA Astrophysics Data System (ADS)

Banerjee, Arup; Biswas, Amiya; Joshi, Shaunak; Kumar, Ankush; Rehman, Sami; Sharma, Satish; Somani, Sandip; Bhati, Sunil; Karelia, Jitendra; Saxena, Anish; Chowdhury, Arup R.

2016-04-01

SW-MW Imaging Infrared Spectrometer, the Hyperspectral optical imaging instrument is envisaged to map geomorphology and mineralogy of lunar surface. The instrument is designed to image the electro-magnetic energy emanating from moon's surface with high spectral and spatial resolution for the mission duration from an altitude of 100 km. It is designed to cover 0.8 to 5 μm in 250 spectral bands with GSD 80m and swath 20km. Primarily, there are three basic optical segments in the spectrometer. They are fore optics, dispersing element and focusing elements. The payload is designed around a custom developed multi-blaze convex grating optimized for system throughput. The considerations for optimization are lunar radiation, instrument background, optical throughput, and detector sensitivity. HgCdTe (cooled using a rotary stirling cooler) based detector array (500x256 elements, 30μm) is being custom developed for the spectrometer. Stray light background flux is minimized using a multi-band filter cooled to cryogenic temperature. Mechanical system realization is being performed considering requirements such as structural, opto-mechanical, thermal, and alignment. The entire EOM is planned to be maintained at 240K to reduce and control instrument background. Al based mirror, grating, and EOM housing is being developed to maintain structural requirements along with opto- mechanical and thermal. Multi-tier radiative isolation and multi-stage radiative cooling approach is selected for maintaining the EOM temperature. EOM along with precision electronics packages are planned to be placed on the outer and inner side of Anti-sun side (ASS) deck. Power and Cooler drive electronics packages are planned to be placed on bottom side of ASS panel. Cooler drive electronics is being custom developed to maintain the detector temperature within 100mK during the imaging phase. Low noise detector electronics development is critical for maintaining the NETD requirements at different target

1E7-03, a low MW compound targeting host protein phosphatase-1, inhibits HIV-1 transcription

PubMed Central

Ammosova, Tatyana; Platonov, Maxim; Ivanov, Andrei; Kont, Yasemin Saygideğer; Kumari, Namita; Kehn-Hall, Kylene; Jerebtsova, Marina; Kulkarni, Amol A; Üren, Aykut; Kovalskyy, Dmytro; Nekhai, Sergei

2014-01-01

Background and Purpose HIV-1 transcription is activated by the Tat protein which recruits the cyclin-dependent kinase CDK9/cyclin T1 to TAR RNA. Tat binds to protein phosphatase-1 (PP1) through the Q35VCF38 sequence and translocates PP1 to the nucleus. PP1 dephosphorylates CDK9 and activates HIV-1 transcription. We have synthesized a low MW compound 1H4, that targets PP1 and prevents HIV-1 Tat interaction with PP1 and inhibits HIV-1 gene transcription. Here, we report our further work with the 1H4-derived compounds and analysis of their mechanism of action. Experimental Approach Using the 1H4-PP1 complex as a model, we iteratively designed and synthesized follow-up libraries that were analysed for the inhibition of HIV-1 transcription and toxicity. We also confirmed the mechanism of action of the PP1-targeting molecules by determining the affinity of binding of these molecules to PP1, by analysing their effects on PP1 activity, disruption of PP1 binding to Tat and shuttling of PP1 to the nucleus. Key Results We identified a tetrahydroquinoline derivative, compound 7, which disrupted the interaction of Tat with PP1. We further optimized compound 7 and obtained compound 7c, renamed 1E7-03, which inhibited HIV-1 with low IC50 (fivefold lower than the previously reported compound, 1H4), showed no cytotoxicity and displayed a plasma half-life greater than 8 h in mice. 1E7-03 bound to PP1 in vitro and prevented shuttling of PP1 into the nucleus. Conclusions and Implications Our study shows that low MW compounds that functionally mimic the PP1-binding RVxF peptide can inhibit HIV-1 transcription by deregulating PP1. PMID:25073485

76 FR 58074 - 30-Day Notice of Proposed Information Collection: DS-7001 and DS-7005, DOS-Sponsored Academic...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-19

...-7001 and DS- 7005, DOS-Sponsored Academic Exchange Program Application, OMB Control Number 1405-0138.... Title of Information Collection: DOS-Sponsored Academic Exchange Program Application. OMB Control Number... Academic Exchange Program. Estimated Number of Respondents: 7160 (For DS-7001, 3842 estimated; for DS-7005...

Real-time capture of seismic waves using high-rate multi-GNSS observations: Application to the 2015 Mw 7.8 Nepal earthquake

NASA Astrophysics Data System (ADS)

Geng, Tao; Xie, Xin; Fang, Rongxin; Su, Xing; Zhao, Qile; Liu, Gang; Li, Heng; Shi, Chuang; Liu, Jingnan

2016-01-01

The variometric approach is investigated to measure real-time seismic waves induced by the 2015 Mw 7.8 Nepal earthquake with high-rate multi-GNSS observations, especially with the contribution of newly available BDS. The velocity estimation using GPS + BDS shows an additional improvement of around 20% with respect to GPS-only solutions. We also reconstruct displacements by integrating GNSS-derived velocities after a linear trend removal (IGV). The displacement waveforms with accuracy of better than 5 cm are derived when postprocessed GPS precise point positioning results are used as ground truth, even if those stations have strong ground motions and static offsets of up to 1-2 m. GNSS-derived velocity and displacement waveforms with the variometric approach are in good agreement with results from strong motion data. We therefore conclude that it is feasible to capture real-time seismic waves with multi-GNSS observations using the IGV-enhanced variometric approach, which has critical implications for earthquake early warning, tsunami forecasting, and rapid hazard assessment.

System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

PubMed

Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

2014-08-01

The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

76 FR 25733 - 60-Day Notice of Proposed Information Collection: DS-7001 and DS-7005, DOS-Sponsored Academic...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-05

... and DS- 7005, DOS-Sponsored Academic Exchange Program Application, OMB Control Number 1405-0138 ACTION... Collection: DOS-Sponsored Academic Exchange Program Application. OMB Control Number: 1405-0138. Type of... Cultural Affairs, ECA/A/E/EUR. Form Number: DS-7001, DS-7005. Respondents: Applicants for the Academic...

Non-Invasive Delivery of dsRNA into De-Waxed Tick Eggs by Electroporation

PubMed Central

Ruiz, Newton; de Abreu, Leonardo Araujo; Parizi, Luís Fernando; Kim, Tae Kwon; Mulenga, Albert; Braz, Gloria Regina Cardoso; Vaz, Itabajara da Silva; Logullo, Carlos

2015-01-01

RNA interference-mediated gene silencing was shown to be an efficient tool for validation of targets that may become anti-tick vaccine components. Here, we demonstrate the application of this approach in the validation of components of molecular signaling cascades, such as the Protein Kinase B (AKT) / Glycogen Synthase Kinase (GSK) axis during tick embryogenesis. It was shown that heptane and hypochlorite treatment of tick eggs can remove wax, affecting corium integrity and but not embryo development. Evidence of AKT and GSK dsRNA delivery into de-waxed eggs of via electroporation is provided. Primers designed to amplify part of the dsRNA delivered into the electroporated eggs dsRNA confirmed its entry in eggs. In addition, it was shown that electroporation is able to deliver the fluorescent stain, 4',6-diamidino-2-phenylindole (DAPI). To confirm gene silencing, a second set of primers was designed outside the dsRNA sequence of target gene. In this assay, the suppression of AKT and GSK transcripts (approximately 50% reduction in both genes) was demonstrated in 7-day-old eggs. Interestingly, silencing of GSK in 7-day-old eggs caused 25% reduction in hatching. Additionally, the effect of silencing AKT and GSK on embryo energy metabolism was evaluated. As expected, knockdown of AKT, which down regulates GSK, the suppressor of glycogen synthesis, decreased glycogen content in electroporated eggs. These data demonstrate that electroporation of de-waxed R. microplus eggs could be used for gene silencing in tick embryos, and improve the knowledge about arthropod embryogenesis. PMID:26091260

Robust Target Tracking with Multi-Static Sensors under Insufficient TDOA Information.

PubMed

Shin, Hyunhak; Ku, Bonhwa; Nelson, Jill K; Ko, Hanseok

2018-05-08

This paper focuses on underwater target tracking based on a multi-static sonar network composed of passive sonobuoys and an active ping. In the multi-static sonar network, the location of the target can be estimated using TDOA (Time Difference of Arrival) measurements. However, since the sensor network may obtain insufficient and inaccurate TDOA measurements due to ambient noise and other harsh underwater conditions, target tracking performance can be significantly degraded. We propose a robust target tracking algorithm designed to operate in such a scenario. First, track management with track splitting is applied to reduce performance degradation caused by insufficient measurements. Second, a target location is estimated by a fusion of multiple TDOA measurements using a Gaussian Mixture Model (GMM). In addition, the target trajectory is refined by conducting a stack-based data association method based on multiple-frames measurements in order to more accurately estimate target trajectory. The effectiveness of the proposed method is verified through simulations.

Construction, completion, and testing of replacement monitoring wells MW 3-2, MW 6-2, MW 7-2, and MW 11-2, Mountain Home Air Force Base, Idaho, February through April 2000

USGS Publications Warehouse

Parliman, D.J.

2000-01-01

In February and March 2000, the U.S. Geological Survey Western Regional Research Drilling Operation constructed replacement monitoring wells MW 3–2, MW 6–2, MW 7–2, and MW 11–2 as part of a regional ground-water monitor- ing network for the Mountain Home Air Force Base, Elmore County, Idaho. Total well depths ranged from 435.5 to 456.5 feet, and initial depth-to-water measurements ranged from about 350 to 375 feet below land surface. After completion, wells were pumped and onsite measurements were made of water temperature, specific conductance, pH, and dissolved oxygen. At each well, natural gamma, spontaneous potential, resistivity, caliper, and temperature logs were obtained from instruments placed in open boreholes. A three- dimensional borehole flow analysis was completed for MW 3–2 and MW 11–2, and a video log was obtained for MW 11–2 to annotate lithology and note wet zones in the borehole above saturated rock.

Thermal-hydraulic simulation of mercury target concepts for a pulsed spallation neutron source

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

Siman-Tov, M.; Wendel, M.; Haines, J.

1996-06-01

The Oak Ridge Spallation Neutron Source (ORSNS) is a high-power, accelerator-based pulsed spallation neutron source being designed by a multi-laboratory team led by Oak Ridge National Laboratory to achieve very high fluxes of neutrons for scientific experiments. The ORSNS is projected to have a 1 MW proton beam upgradable to 5 MW. About 60% of the beam power (1-5 MW, 17-83 kJ/pulse in 0.5 microsec at 60 cps) is deposited in the liquid metal (mercury) target having the dimensions of 65x30x10 cm (about 19.5 liter). Peak steady state power density is about 150 and 785 MW/m{sup 3} for 1 MWmore » and 5 MW beam respectively, whereas peak pulsed power density is as high as 5.2 and 26.1 GW/m{sup 3}, respectively. The peak pulse temperature rise rate is 14 million C/s (for 5 MW beam) whereas the total pulse temperature rise is only 7 C. In addition to thermal shock and materials compatibility, key feasibility issues for the target are related to its thermal-hydraulic performance. This includes proper flow distribution, flow reversals, possible {open_quotes}hot spots{close_quotes} and the challenge of mitigating the effects of thermal shock through possible injection of helium bubbles throughout the mercury volume or other concepts. The general computational fluid dynamics (CFD) code CFDS-FLOW3D was used to simulate the thermal and flow distribution in three preliminary concepts of the mercury target. Very initial CFD simulation of He bubbles injection demonstrates some potential for simulating behavior of He bubbles in flowing mercury. Much study and development will be required to be able to `predict`, even in a crude way, such a complex phenomena. Future direction in both design and R&D is outlined.« less

Low Beam Voltage, 10 MW, L-Band Cluster Klystron

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

Teryaev, V.; /Novosibirsk, IYF; Yakovlev, V.P.

2009-05-01

Conceptual design of a multi-beam klystron (MBK) for possible ILC and Project X applications is presented. The chief distinction between this MBK design and existing 10-MW MBK's is the low operating voltage of 60 kV. There are at least four compelling reasons that justify development at this time of a low-voltage MBK, namely (1) no pulse transformer; (2) no oil tank for high-voltage components and for the tube socket; (3) no high-voltage cables; and (4) modulator would be a compact 60-kV IGBT switching circuit. The proposed klystron consists of four clusters containing six beams each. The tube has common inputmore » and output cavities for all 24 beams, and individual gain cavities for each cluster. A closely related optional configuration, also for a 10 MW tube, would involve four totally independent cavity clusters with four independent input cavities and four 2.5 MW output ports, all within a common magnetic circuit. This option has appeal because the output waveguides would not require a controlled atmosphere, and because it would be easier to achieve phase and amplitude stability as required in individual SC accelerator cavities.« less

Earthquake cycle modeling of multi-segmented faults: dynamic rupture and ground motion simulation of the 1992 Mw 7.3 Landers earthquake.

NASA Astrophysics Data System (ADS)

Petukhin, A.; Galvez, P.; Somerville, P.; Ampuero, J. P.

2017-12-01

We perform earthquake cycle simulations to study the characteristics of source scaling relations and strong ground motions and in multi-segmented fault ruptures. For earthquake cycle modeling, a quasi-dynamic solver (QDYN, Luo et al, 2016) is used to nucleate events and the fully dynamic solver (SPECFEM3D, Galvez et al., 2014, 2016) is used to simulate earthquake ruptures. The Mw 7.3 Landers earthquake has been chosen as a target earthquake to validate our methodology. The SCEC fault geometry for the three-segmented Landers rupture is included and extended at both ends to a total length of 200 km. We followed the 2-D spatial correlated Dc distributions based on Hillers et. al. (2007) that associates Dc distribution with different degrees of fault maturity. The fault maturity is related to the variability of Dc on a microscopic scale. Large variations of Dc represents immature faults and lower variations of Dc represents mature faults. Moreover we impose a taper (a-b) at the fault edges and limit the fault depth to 15 km. Using these settings, earthquake cycle simulations are performed to nucleate seismic events on different sections of the fault, and dynamic rupture modeling is used to propagate the ruptures. The fault segmentation brings complexity into the rupture process. For instance, the change of strike between fault segments enhances strong variations of stress. In fact, Oglesby and Mai (2012) show the normal stress varies from positive (clamping) to negative (unclamping) between fault segments, which leads to favorable or unfavorable conditions for rupture growth. To replicate these complexities and the effect of fault segmentation in the rupture process, we perform earthquake cycles with dynamic rupture modeling and generate events similar to the Mw 7.3 Landers earthquake. We extract the asperities of these events and analyze the scaling relations between rupture area, average slip and combined area of asperities versus moment magnitude. Finally, the

RDE-4 preferentially binds long dsRNA and its dimerization is necessary for cleavage of dsRNA to siRNA.

PubMed

Parker, Greg S; Eckert, Debra M; Bass, Brenda L

2006-05-01

In organisms ranging from Arabidopsis to humans, Dicer requires dsRNA-binding proteins (dsRBPs) to carry out its roles in RNA interference (RNAi) and micro-RNA (miRNA) processing. In Caenorhabditis elegans, the dsRBP RDE-4 acts with Dicer during the initiation of RNAi, when long dsRNA is cleaved to small interfering RNAs (siRNAs). RDE-4 is not required in subsequent steps, and how RDE-4 distinguishes between long dsRNA and short siRNA is unclear. We report the first detailed analysis of RDE-4 binding, using purified recombinant RDE-4 and various truncated proteins. We find that, similar to other dsRBPs, RDE-4 is not sequence-specific. However, consistent with its in vivo roles, RDE-4 binds with higher affinity to long dsRNA. We also observe that RDE-4 is a homodimer in solution, and that the C-terminal domain of the protein is required for dimerization. Using extracts from wild-type and rde-4 mutant C. elegans, we show that the C-terminal dimerization domain is required for the production of siRNA. Our findings suggest a model for RDE-4 function during the initiation of RNAi.

RDE-4 preferentially binds long dsRNA and its dimerization is necessary for cleavage of dsRNA to siRNA

PubMed Central

Parker, Greg S.; Eckert, Debra M.; Bass, Brenda L.

2006-01-01

In organisms ranging from Arabidopsis to humans, Dicer requires dsRNA-binding proteins (dsRBPs) to carry out its roles in RNA interference (RNAi) and micro-RNA (miRNA) processing. In Caenorhabditis elegans, the dsRBP RDE-4 acts with Dicer during the initiation of RNAi, when long dsRNA is cleaved to small interfering RNAs (siRNAs). RDE-4 is not required in subsequent steps, and how RDE-4 distinguishes between long dsRNA and short siRNA is unclear. We report the first detailed analysis of RDE-4 binding, using purified recombinant RDE-4 and various truncated proteins. We find that, similar to other dsRBPs, RDE-4 is not sequence-specific. However, consistent with its in vivo roles, RDE-4 binds with higher affinity to long dsRNA. We also observe that RDE-4 is a homodimer in solution, and that the C-terminal domain of the protein is required for dimerization. Using extracts from wild-type and rde-4 mutant C. elegans, we show that the C-terminal dimerization domain is required for the production of siRNA. Our findings suggest a model for RDE-4 function during the initiation of RNAi. PMID:16603715

Noninvasive and real-time monitoring of molecular targeting therapy for lymph node and peritoneal metastasis in nude mice bearing xenografts of human colorectal cancer cells tagged with GFP and DsRed

NASA Astrophysics Data System (ADS)

Nakanishi, Hayao; Hara, Masayasu; Ikehara, Yuzuru; Tatematsu, Masae

2007-02-01

We have developed an in vivo imaging system consisting of GFP- and DsRed-tagged human colonic cancer cell line, which has peritoneal and lymph node metastatic potential and show high sensitivity to EGFR targeting drugs, and convenient detection devices for GFP and DsRed. The latter includes a small handy fluorescence detection device for external monitoring of the therapeutic effect of the drug and a convenient stereo fluorescent microscope for internal visualization of micrometastases. We applied this imaging system to investigate anti-metastatic effects of EGFR targeting drugs such as gefitinib (Iressa). This system allowed sensitive detection of the development of peritoneal and lymph node metastases from the micrometastasis stage at the cellular level and also permited noninvasive, non-anesthetic monitoring of anti-metastatic effect of the drug in an animal facility without any pretreatment. Significant decreases in the intraabdominal metastatic tumor growth and prevention of inguinal lymph node metastasis by gefitinib treatment could be clearly monitored. These results suggest that convenient, low-cost, true real-time monitoring of therapeutic effect using such a fluorescence-mediated whole body imaging system seems to enhance the speed of preclinical study for novel anti-cancer agents and will allow us to understand the action mechanism of molecular targeting drugs.

First Observation of the Decay Ds+→p nmacr

NASA Astrophysics Data System (ADS)

Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Mehrabyan, S.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Libby, J.; Powell, A.; Wilkinson, G.; Ecklund, K. M.; Love, W.; Savinov, V.; Lopez, A.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sultana, N.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, L. M.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Naik, P.; Rademacker, J.; Asner, D. M.; Edwards, K. W.; Reed, J.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Hunt, J. M.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Ledoux, J.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.

2008-05-01

Using e+e-→Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170MeV, with the CLEO-c detector, we present the first observation of the decay Ds+→p nmacr . We measure a branching fraction B(Ds+→p nmacr )=(1.30±0.36-0.16+0.12)×10-3. This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

A novel mycovirus from Aspergillus fumigatus contains four unique dsRNAs as its genome and is infectious as dsRNA

PubMed Central

Kanhayuwa, Lakkhana; Kotta-Loizou, Ioly; Özkan, Selin; Gunning, A. Patrick; Coutts, Robert H. A.

2015-01-01

We report the discovery and characterization of a double-stranded RNA (dsRNA) mycovirus isolated from the human pathogenic fungus Aspergillus fumigatus, Aspergillus fumigatus tetramycovirus-1 (AfuTmV-1), which reveals several unique features not found previously in positive-strand RNA viruses, including the fact that it represents the first dsRNA (to our knowledge) that is not only infectious as a purified entity but also as a naked dsRNA. The AfuTmV-1 genome consists of four capped dsRNAs, the largest of which encodes an RNA-dependent RNA polymerase (RdRP) containing a unique GDNQ motif normally characteristic of negative-strand RNA viruses. The third largest dsRNA encodes an S-adenosyl methionine–dependent methyltransferase capping enzyme and the smallest dsRNA a P-A-S–rich protein that apparently coats but does not encapsidate the viral genome as visualized by atomic force microscopy. A combination of a capping enzyme with a picorna-like RdRP in the AfuTmV-1 genome is a striking case of chimerism and the first example (to our knowledge) of such a phenomenon. AfuTmV-1 appears to be intermediate between dsRNA and positive-strand ssRNA viruses, as well as between encapsidated and capsidless RNA viruses. PMID:26139522

Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma

PubMed Central

Arnhold, Viktor; Schmelz, Karin; Proba, Jutta; Winkler, Annika; Wünschel, Jasmin; Toedling, Joern; Deubzer, Hedwig E.; Künkele, Annette; Eggert, Angelika; Schulte, Johannes H.; Hundsdoerfer, Patrick

2018-01-01

Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients. Toxic side effects, poor bioavailability and low efficacy of the available MDM2 inhibitors that have entered phase I/II trials drive the development of novel MDM2 inhibitors with an improved risk-benefit profile. We investigated the effect of the novel MDM2 small molecular inhibitor, DS-3032b, on viability, proliferation, senescence, migration, cell cycle arrest and apoptosis in a panel of six neuroblastoma cell lines with different TP53 and MYCN genetic backgrounds, and assessed efficacy in a murine subcutaneous model for high-risk neuroblastoma. Re-analysis of existing expression data from 476 primary neuroblastomas showed that high-level MDM2 expression correlated with poor patient survival. DS-3032b treatment enhanced TP53 target gene expression and induced G1 cell cycle arrest, senescence and apoptosis. CRISPR-mediated MDM2 knockout in neuroblastoma cells mimicked DS-3032b treatment. TP53 signaling was selectively activated by DS-3032b in neuroblastoma cells with wildtype TP53, regardless of the presence of MYCN amplification, but was significantly reduced by TP53 mutations or expression of a dominant-negative TP53 mutant. Oral DS-3032b administration inhibited xenograft tumor growth and prolonged mouse survival. Our in vitro and in vivo data demonstrate that DS-3032b reactivates TP53 signaling even in the presence of MYCN amplification in neuroblastoma cells, to reduce proliferative capacity and cause cytotoxicity. PMID:29416773

Target and (Astro-)WISE technologies Data federations and its applications

NASA Astrophysics Data System (ADS)

Valentijn, E. A.; Begeman, K.; Belikov, A.; Boxhoorn, D. R.; Brinchmann, J.; McFarland, J.; Holties, H.; Kuijken, K. H.; Verdoes Kleijn, G.; Vriend, W.-J.; Williams, O. R.; Roerdink, J. B. T. M.; Schomaker, L. R. B.; Swertz, M. A.; Tsyganov, A.; van Dijk, G. J. W.

2017-06-01

After its first implementation in 2003 the Astro-WISE technology has been rolled out in several European countries and is used for the production of the KiDS survey data. In the multi-disciplinary Target initiative this technology, nicknamed WISE technology, has been further applied to a large number of projects. Here, we highlight the data handling of other astronomical applications, such as VLT-MUSE and LOFAR, together with some non-astronomical applications such as the medical projects Lifelines and GLIMPS; the MONK handwritten text recognition system; and business applications, by amongst others, the Target Holding. We describe some of the most important lessons learned and describe the application of the data-centric WISE type of approach to the Science Ground Segment of the Euclid satellite.

Synthetic biology approach for plant protection using dsRNA.

PubMed

Niehl, Annette; Soininen, Marjukka; Poranen, Minna M; Heinlein, Manfred

2018-02-26

Pathogens induce severe damages on cultivated plants and represent a serious threat to global food security. Emerging strategies for crop protection involve the external treatment of plants with double-stranded (ds)RNA to trigger RNA interference. However, applying this technology in greenhouses and fields depends on dsRNA quality, stability and efficient large-scale production. Using components of the bacteriophage phi6, we engineered a stable and accurate in vivo dsRNA production system in Pseudomonas syringae bacteria. Unlike other in vitro or in vivo dsRNA production systems that rely on DNA transcription and postsynthetic alignment of single-stranded RNA molecules, the phi6 system is based on the replication of dsRNA by an RNA-dependent RNA polymerase, thus allowing production of high-quality, long dsRNA molecules. The phi6 replication complex was reprogrammed to multiply dsRNA sequences homologous to tobacco mosaic virus (TMV) by replacing the coding regions within two of the three phi6 genome segments with TMV sequences and introduction of these constructs into P. syringae together with the third phi6 segment, which encodes the components of the phi6 replication complex. The stable production of TMV dsRNA was achieved by combining all the three phi6 genome segments and by maintaining the natural dsRNA sizes and sequence elements required for efficient replication and packaging of the segments. The produced TMV-derived dsRNAs inhibited TMV propagation when applied to infected Nicotiana benthamiana plants. The established dsRNA production system enables the broad application of dsRNA molecules as an efficient, highly flexible, nontransgenic and environmentally friendly approach for protecting crops against viruses and other pathogens. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Joint Frequency-Domain Equalization and Despreading for Multi-Code DS-CDMA Using Cyclic Delay Transmit Diversity

NASA Astrophysics Data System (ADS)

Yamamoto, Tetsuya; Takeda, Kazuki; Adachi, Fumiyuki

Frequency-domain equalization (FDE) based on the minimum mean square error (MMSE) criterion can provide a better bit error rate (BER) performance than rake combining. To further improve the BER performance, cyclic delay transmit diversity (CDTD) can be used. CDTD simultaneously transmits the same signal from different antennas after adding different cyclic delays to increase the number of equivalent propagation paths. Although a joint use of CDTD and MMSE-FDE for direct sequence code division multiple access (DS-CDMA) achieves larger frequency diversity gain, the BER performance improvement is limited by the residual inter-chip interference (ICI) after FDE. In this paper, we propose joint FDE and despreading for DS-CDMA using CDTD. Equalization and despreading are simultaneously performed in the frequency-domain to suppress the residual ICI after FDE. A theoretical conditional BER analysis is presented for the given channel condition. The BER analysis is confirmed by computer simulation.

Multifractal analysis of 2001 Mw 7 . 7 Bhuj earthquake sequence in Gujarat, Western India

NASA Astrophysics Data System (ADS)

Aggarwal, Sandeep Kumar; Pastén, Denisse; Khan, Prosanta Kumar

2017-12-01

The 2001 Mw 7 . 7 Bhuj mainshock seismic sequence in the Kachchh area, occurring during 2001 to 2012, has been analyzed using mono-fractal and multi-fractal dimension spectrum analysis technique. This region was characterized by frequent moderate shocks of Mw ≥ 5 . 0 for more than a decade since the occurrence of 2001 Bhuj earthquake. The present study is therefore important for precursory analysis using this sequence. The selected long-sequence has been investigated first time for completeness magnitude Mc 3.0 using the maximum curvature method. Multi-fractal Dq spectrum (Dq ∼ q) analysis was carried out using effective window-length of 200 earthquakes with a moving window of 20 events overlapped by 180 events. The robustness of the analysis has been tested by considering the magnitude completeness correction term of 0.2 to Mc 3.0 as Mc 3.2 and we have tested the error in the calculus of Dq for each magnitude threshold. On the other hand, the stability of the analysis has been investigated down to the minimum magnitude of Mw ≥ 2 . 6 in the sequence. The analysis shows the multi-fractal dimension spectrum Dq decreases with increasing of clustering of events with time before a moderate magnitude earthquake in the sequence, which alternatively accounts for non-randomness in the spatial distribution of epicenters and its self-organized criticality. Similar behavior is ubiquitous elsewhere around the globe, and warns for proximity of a damaging seismic event in an area. OS: Please confirm math roman or italics in abs.

Use of geological mapping tools to improve the hydraulic performance of SuDS.

PubMed

Bockhorn, Britta; Klint, Knud Erik Strøyberg; Jensen, Marina Bergen; Møller, Ingelise

2015-01-01

Most cities in Denmark are situated on low permeable clay rich deposits. These sediments are of glacial origin and range among the most heterogeneous, with hydraulic conductivities spanning several orders of magnitude. This heterogeneity has obvious consequences for the sizing of sustainable urban drainage systems (SuDS). We have tested methods to reveal geological heterogeneity at field scale to identify the most suitable sites for the placement of infiltration elements and to minimize their required size. We assessed the geological heterogeneity of a clay till plain in Eastern Jutland, Denmark measuring the shallow subsurface resistivity with a geoelectrical multi-electrode system. To confirm the resistivity data we conducted a spear auger mapping. The exposed sediments ranged from clay tills over sandy clay tills to sandy tills and correspond well to the geoelectrical data. To verify the value of geological information for placement of infiltration elements we carried out a number of infiltration tests on geologically different areas across the field, and we observed infiltration rates two times higher in the sandy till area than in the clay till area, thus demonstrating that the hydraulic performance of SuDS can be increased considerably and oversizing avoided if field geological heterogeneity is revealed before placing SuDS.

CCD Spectroscopy and Photometry of the DS1 Flyby Target P/Borrelly.

NASA Astrophysics Data System (ADS)

Hicks, M. D.; Buratti, B. J.; Esqueda, D.; Ha, E.; Pass, R. P., III

2001-11-01

In support of the Deep Space 1 encounter with the comet P/Borrelly on Sep 23 2001, we have been engaged in a vigorous campaign of ground-based observations on telescopes ranging in aperture from 10 inches (for rough R-magnitudes) to 200 (for medium resolution spectrophotometry). We present our preliminary analysis and discuss our results in the context of the successful DS1 flyby. On the nights of July 26 and Sep 16-17 we obtained long-slit spectrograms of the comet at the Palomar 200-inch using the facility ``Double Spec'' with a resolution of ~3 angstrom and a wavelength range between ~0.38 and 0.90 micron. We can compute the production rates of H2O, CN, C2, C3, and NH2. We shall compare the production rate ratios of Borrelly to values obtained in previous apparitions and to the ensemble of comets. Our broad-band photometry of the coma began ias soon as the comet was availible from our latitude in early July and continued until a few days before encounter. The R-band magnitudes where converted to a dust production rate through the Afrho formalism. The astrometry was reduced and submitted to to MPC and the JPL Solar System Dynamics group throughout the apparition. The astrometry obtained at the P200 on Sep 16 proved especially helpful to mission planners, due to its high spatial resolution and nearly perpendicular point of view from the DS1 line of sight. The photometric data was collected by an ecclectic mix of professionals, undergraduate students, and a dedicated amatuer observer. This work was funded by NASA, with the stipend for the student observers coming from the NASA/NSF CURE program.

Identification and characterization of carprofen as a multi-target FAAH/COX inhibitor

PubMed Central

Favia, Angelo D.; Habrant, Damien; Scarpelli, Rita; Migliore, Marco; Albani, Clara; Bertozzi, Sine Mandrup; Dionisi, Mauro; Tarozzo, Glauco; Piomelli, Daniele; Cavalli, Andrea; De Vivo, Marco

2013-01-01

Pain and inflammation are major therapeutic areas for drug discovery. Current drugs for these pathologies have limited efficacy, however, and often cause a number of unwanted side effects. In the present study, we identify the non-steroid anti-inflammatory drug, carprofen, as a multi-target-directed ligand that simultaneously inhibits cyclooxygenase-1 (COX-1), COX-2 and fatty acid amide hydrolase (FAAH). Additionally, we synthesized and tested several racemic derivatives of carprofen, sharing this multi-target activity. This may result in improved analgesic efficacy and reduced side effects (Naidu, et al (2009) J Pharmacol Exp Ther 329, 48-56; Fowler, C.J. et al. (2012) J Enzym Inhib Med Chem Jan 6; Sasso, et al (2012) Pharmacol Res 65, 553). The new compounds are among the most potent multi-target FAAH/COXs inhibitors reported so far in the literature, and thus may represent promising starting points for the discovery of new analgesic and anti-inflammatory drugs. PMID:23043222

Application of data fusion technology based on D-S evidence theory in fire detection

NASA Astrophysics Data System (ADS)

Cai, Zhishan; Chen, Musheng

2015-12-01

Judgment and identification based on single fire characteristic parameter information in fire detection is subject to environmental disturbances, and accordingly its detection performance is limited with the increase of false positive rate and false negative rate. The compound fire detector employs information fusion technology to judge and identify multiple fire characteristic parameters in order to improve the reliability and accuracy of fire detection. The D-S evidence theory is applied to the multi-sensor data-fusion: first normalize the data from all sensors to obtain the normalized basic probability function of the fire occurrence; then conduct the fusion processing using the D-S evidence theory; finally give the judgment results. The results show that the method meets the goal of accurate fire signal identification and increases the accuracy of fire alarm, and therefore is simple and effective.

DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1.

PubMed

Ogitani, Yusuke; Aida, Tetsuo; Hagihara, Katsunobu; Yamaguchi, Junko; Ishii, Chiaki; Harada, Naoya; Soma, Masako; Okamoto, Hiromi; Oitate, Masataka; Arakawa, Shingo; Hirai, Takehiro; Atsumi, Ryo; Nakada, Takashi; Hayakawa, Ichiro; Abe, Yuki; Agatsuma, Toshinori

2016-10-15

An anti-HER2 antibody-drug conjugate with a novel topoisomerase I inhibitor, DS-8201a, was generated as a new antitumor drug candidate, and its preclinical pharmacologic profile was assessed. In vitro and in vivo pharmacologic activities of DS-8201a were evaluated and compared with T-DM1 in several HER2-positive cell lines and patient-derived xenograft (PDX) models. The mechanism of action for the efficacy was also evaluated. Pharmacokinetics in cynomolgus monkeys and the safety profiles in rats and cynomolgus monkeys were assessed. DS-8201a exhibited a HER2 expression-dependent cell growth-inhibitory activity and induced tumor regression with a single dosing at more than 1 mg/kg in a HER2-positive gastric cancer NCI-N87 model. Binding activity to HER2 and ADCC activity of DS-8201a were comparable with unconjugated anti-HER2 antibody. DS-8201a also showed an inhibitory activity to Akt phosphorylation. DS-8201a induced phosphorylation of Chk1 and Histone H2A.X, the markers of DNA damage. Pharmacokinetics and safety profiles of DS-8201a were favorable and the highest non-severely toxic dose was 30 mg/kg in cynomolgus monkeys, supporting DS-8201a as being well tolerated in humans. DS-8201a was effective in a T-DM1-insensitive PDX model with high HER2 expression. DS-8201a, but not T-DM1, demonstrated antitumor efficacy against several breast cancer PDX models with low HER2 expression. DS-8201a exhibited a potent antitumor activity in a broad selection of HER2-positive models and favorable pharmacokinetics and safety profiles. The results demonstrate that DS-8201a will be a valuable therapy with a great potential to respond to T-DM1-insensitive HER2-positive cancers and low HER2-expressing cancers. Clin Cancer Res; 22(20); 5097-108. ©2016 AACR. ©2016 American Association for Cancer Research.

A Parallel Finite Set Statistical Simulator for Multi-Target Detection and Tracking

NASA Astrophysics Data System (ADS)

Hussein, I.; MacMillan, R.

2014-09-01

Finite Set Statistics (FISST) is a powerful Bayesian inference tool for the joint detection, classification and tracking of multi-target environments. FISST is capable of handling phenomena such as clutter, misdetections, and target birth and decay. Implicit within the approach are solutions to the data association and target label-tracking problems. Finally, FISST provides generalized information measures that can be used for sensor allocation across different types of tasks such as: searching for new targets, and classification and tracking of known targets. These FISST capabilities have been demonstrated on several small-scale illustrative examples. However, for implementation in a large-scale system as in the Space Situational Awareness problem, these capabilities require a lot of computational power. In this paper, we implement FISST in a parallel environment for the joint detection and tracking of multi-target systems. In this implementation, false alarms and misdetections will be modeled. Target birth and decay will not be modeled in the present paper. We will demonstrate the success of the method for as many targets as we possibly can in a desktop parallel environment. Performance measures will include: number of targets in the simulation, certainty of detected target tracks, computational time as a function of clutter returns and number of targets, among other factors.

CfDS: a team effort

NASA Astrophysics Data System (ADS)

Mizon, R.

2003-02-01

In 1989, the newly formed BAA Campaign for Dark Skies (CfDS) asked astronomical groups across the UK to nominate members who would actively spread the dark-skies message. Thirty-one 'regional officers' emerged, scattered from Plymouth to near John O'Groats, and from North Wales to the Wash. An unenviable task faced them: a CfDS survey had concluded that more than 90% of British observers, astronomers or not, experienced some degree of skyglow.

Multi-MW accelerator target material properties under proton irradiation at Brookhaven National Laboratory linear isotope producer

DOE PAGES

Simos, N.; Ludewig, H.; Kirk, H.; ...

2018-05-29

The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory’s (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest inmore » assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.« less

Multi-MW accelerator target material properties under proton irradiation at Brookhaven National Laboratory linear isotope producer

NASA Astrophysics Data System (ADS)

Simos, N.; Ludewig, H.; Kirk, H.; Dooryhee, E.; Ghose, S.; Zhong, Z.; Zhong, H.; Makimura, S.; Yoshimura, K.; Bennett, J. R. J.; Kotsinas, G.; Kotsina, Z.; McDonald, K. T.

2018-05-01

The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory's (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest in assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.

Multi-MW accelerator target material properties under proton irradiation at Brookhaven National Laboratory linear isotope producer

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

Simos, N.; Ludewig, H.; Kirk, H.

The effects of proton beams irradiating materials considered for targets in high-power accelerator experiments have been studied using the Brookhaven National Laboratory’s (BNL) 200 MeV proton linac. A wide array of materials and alloys covering a wide range of the atomic number (Z) are being scoped by the high-power accelerator community prompting the BNL studies to focus on materials representing each distinct range, i.e. low-Z, mid-Z and high-Z. The low range includes materials such as beryllium and graphite, the midrange alloys such as Ti-6Al-4V, gum metal and super-Invar and finally the high-Z range pure tungsten and tantalum. Of interest inmore » assessing proton irradiation effects are (a) changes in physiomechanical properties which are important in maintaining high-power target functionality, (b) identification of possible limits of proton flux or fluence above which certain materials cease to maintain integrity, (c) the role of material operating temperature in inducing or maintaining radiation damage reversal, and (d) phase stability and microstructural changes. The paper presents excerpt results deduced from macroscopic and microscopic post-irradiation evaluation (PIE) following several irradiation campaigns conducted at the BNL 200 MeV linac and specifically at the isotope producer beam-line/target station. The microscopic PIE relied on high energy x-ray diffraction at the BNL NSLS X17B1 and NSLS II XPD beam lines. The studies reveal the dramatic effects of irradiation on phase stability in several of the materials, changes in physical properties and ductility loss as well as thermally induced radiation damage reversal in graphite and alloys such as super-Invar.« less

Expression of Activating KIR2DS2 and KIR2DS4 genes following hematopoietic cell transplant (HCT): relevance to cytomegalovirus (CMV) infection

PubMed Central

Gallez-Hawkins, Ghislaine M.; Franck, Anne E.; Li, Xiuli; Thao, Lia; Oki, Arisa; Gendzekhadze, Ketevan; Dagis, Andrew; Palmer, Joycelynne; Nakamura, Ryotaro; Forman, Stephen J.; Senitzer, David; Zaia, John A.

2011-01-01

The important role of activating Killer Immunoglobulin-like Receptors (aKIR) in protecting against cytomegalovirus (CMV) reactivation has been described previously in hematopoietic cell transplantation (HCT). More specifically, the presence of multiple aKIR and the presence of at least KIR2DS2 and KIR2DS4 in the donor genotype identified a group of HCT patients that were at low risk for CMV reactivation. However, CMV infection still occurs in patients with KIR protective genotype and the question was raised as to whether this was due to the lack of KIR expression. In this report, the expression of KIR2DS2 and 2DS4 gene, as measured by mRNA-based Q-PCR both in the donor cells and in the HCT recipient cells was studied relative to CMV reactivation. In the control samples from healthy HCT donors, the median range of for KIR2DS2 and KIR2DS4 expression was low with 35% considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT when compared to donor expression prior to transplant, and significantly elevated in the CMV viremic (V) compared to non-viremic (NV) HCT recipients. CMV seropositivity of donors was not associated with aKIR expression, and donor null-expression in those with KIR2DS2 or KIR2DS4 genotype did not predict for CMV reactivation in the recipient. After controlling for other transplant factors that included donor type (sibling or unrelated), transplant source -bone marrow (BM) or peripheral blood stem cells (PB) and acute GVHD grade, the result of the regression analysis of elevated KIR gene expression was found to be associated for both KIR2DS2 and KIR2DS4, with seven fold increase in risk for CMV reactivation. We speculate that the elevated aKIR expression in CMV viremic HCT recipients is either coincidental with factors that activate CMV or is initiated by CMV or cellular processes responsive to such CMV infection reactivation. PMID:21596150

Multi-AUV Target Search Based on Bioinspired Neurodynamics Model in 3-D Underwater Environments.

PubMed

Cao, Xiang; Zhu, Daqi; Yang, Simon X

2016-11-01

Target search in 3-D underwater environments is a challenge in multiple autonomous underwater vehicles (multi-AUVs) exploration. This paper focuses on an effective strategy for multi-AUV target search in the 3-D underwater environments with obstacles. First, the Dempster-Shafer theory of evidence is applied to extract information of environment from the sonar data to build a grid map of the underwater environments. Second, a topologically organized bioinspired neurodynamics model based on the grid map is constructed to represent the dynamic environment. The target globally attracts the AUVs through the dynamic neural activity landscape of the model, while the obstacles locally push the AUVs away to avoid collision. Finally, the AUVs plan their search path to the targets autonomously by a steepest gradient descent rule. The proposed algorithm deals with various situations, such as static targets search, dynamic targets search, and one or several AUVs break down in the 3-D underwater environments with obstacles. The simulation results show that the proposed algorithm is capable of guiding multi-AUV to achieve search task of multiple targets with higher efficiency and adaptability compared with other algorithms.

Identification of highly effective target genes for RNAi-mediated control of emerald ash borer, Agrilus planipennis.

PubMed

Rodrigues, Thais B; Duan, Jian J; Palli, Subba R; Rieske, Lynne K

2018-03-22

Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.

Multi-target screening mines hesperidin as a multi-potent inhibitor: Implication in Alzheimer's disease therapeutics.

PubMed

Chakraborty, Sandipan; Bandyopadhyay, Jaya; Chakraborty, Sourav; Basu, Soumalee

2016-10-04

Alzheimer's disease (AD) is the most frequent form of neurodegenerative disorder in elderly people. Involvement of several pathogenic events and their interconnections make this disease a complex disorder. Therefore, designing compounds that can inhibit multiple toxic pathways is the most attractive therapeutic strategy in complex disorders like AD. Here, we have designed a multi-tier screening protocol combining ensemble docking to mine BACE1 inhibitor, as well as 2-D QSAR models for anti-amyloidogenic and antioxidant activities. An in house developed phytochemical library of 200 phytochemicals has been screened through this multi-target procedure which mine hesperidin, a flavanone glycoside commonly found in citrus food items, as a multi-potent phytochemical in AD therapeutics. Steady-state and time-resolved fluorescence spectroscopy reveal that binding of hesperidin to the active site of BACE1 induces a conformational transition of the protein from open to closed form. Hesperidin docks close to the catalytic aspartate residues and orients itself in a way that blocks the cavity opening thereby precluding substrate binding. Hesperidin is a high affinity BACE1 inhibitor and only 500 nM of the compound shows complete inhibition of the enzyme activity. Furthermore, ANS and Thioflavin-T binding assay show that hesperidin completely inhibits the amyloid fibril formation which is further supported by atomic force microscopy. Hesperidin exhibits moderate ABTS(+) radical scavenging assay but strong hydroxyl radical scavenging ability, as evident from DNA nicking assay. Present study demonstrates the applicability of a novel multi-target screening procedure to mine multi-potent agents from natural origin for AD therapeutics. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Temperature dependence of yields from multi-foil SPES target

NASA Astrophysics Data System (ADS)

Corradetti, S.; Biasetto, L.; Manzolaro, M.; Scarpa, D.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

2011-10-01

The temperature dependence of neutron-rich isotope yields was studied within the framework of the HRIBF-SPES Radioactive Ion Beams (RIB) project. On-line release measurements of fission fragments from a uranium carbide target at ensuremath 1600 {}^{circ}C , ensuremath 1800 {}^{circ}C and ensuremath 2000 {}^{circ}C were performed at ORNL (USA). The fission reactions were induced by a 40MeV proton beam accelerated into a uranium carbide target coupled to a plasma ion source. The experiments allowed for tests of performance of the SPES multi-foil target prototype loaded with seven UC2/graphite discs (ratio C/ U = 4 with density about 4g/cm3.

Assessment of berberine as a multi-target antimicrobial: a multi-omics study for drug discovery and repositioning.

PubMed

Karaosmanoglu, Kubra; Sayar, Nihat Alpagu; Kurnaz, Isil Aksan; Akbulut, Berna Sariyar

2014-01-01

Postgenomics drug development is undergoing major transformation in the age of multi-omics studies and drug repositioning. Rather than applications solely in personalized medicine, omics science thus additionally offers a better understanding of a broader range of drug targets and drug repositioning. Berberine is an isoquinoline alkaloid found in many medicinal plants. We report here a whole genome microarray study in tandem with proteomics techniques for mining the plethora of targets that are putatively involved in the antimicrobial activity of berberine against Escherichia coli. We found DNA replication/repair and transcription to be triggered by berberine, indicating that nucleic acids, in general, are among its targets. Our combined transcriptomics and proteomics multi-omics findings underscore that, in the presence of berberine, cell wall or cell membrane transport and motility-related functions are also specifically regulated. We further report a general decline in metabolism, as seen by repression of genes in carbohydrate and amino acid metabolism, energy production, and conversion. An involvement of multidrug efflux pumps, as well as reduced membrane permeability for developing resistance against berberine in E. coli was noted. Collectively, these findings offer original and significant leads for omics-guided drug discovery and future repositioning approaches in the postgenomics era, using berberine as a multi-omics case study.

In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.

PubMed

Yi, Bong Gu; Park, Ok Kyu; Jeong, Myeong Seon; Kwon, Seung Hae; Jung, Jae In; Lee, Seongsoo; Ryoo, Sungwoo; Kim, Sung Eun; Kim, Jin Won; Moon, Won-Jin; Park, Kyeongsoon

2017-04-01

Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

PubMed

Anusuya, Shanmugam; Natarajan, Jeyakumar

2012-12-01

Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

60-MW test using the 30-MW klystrons for the KEKB project

NASA Astrophysics Data System (ADS)

Fukuda, S.; Michizono, S.; Nakao, K.; Saito, Y.; Anami, S.

1995-07-01

The B-Factory is a future plan, requiring an energy upgrade of the KEK linac from 2.5 GeV to 8.0 GeV (KEKB Project). This paper describes the recent development of an S-band high-power pulse klystron to be used as the PF-linac rf-source of the B-Factory. This tube is a modified version of the existing 30-MW tube, which produces 51 MW at a 310 kV beam voltage by optimizing the focusing magnetic field. In order to increase the reliability, the cathode diameter, the gun housing, and the insulation ceramic-seal were enlarged. This tube was redesigned so as to have the same characteristics as the test results of 30-MW tubes at a higher applied voltage without changing the rf interaction region. Four prototype tubes have been manufactured; final test results showed that these new tubes produce an output power of more than 50 MW at 310 kV with an efficiency of 46%. Recently this tube has produced more than 60 MW at a 350 kV beam voltage for a demonstration test. A comparison between the FCI-code prediction and the test results is also given in this paper.

Knock down of Whitefly Gut Gene Expression and Mortality by Orally Delivered Gut Gene-Specific dsRNAs.

PubMed

Vyas, Meenal; Raza, Amir; Ali, Muhammad Yousaf; Ashraf, Muhammad Aleem; Mansoor, Shahid; Shahid, Ahmad Ali; Brown, Judith K

2017-01-01

Control of the whitefly Bemisia tabaci (Genn.) agricultural pest and plant virus vector relies on the use of chemical insecticides. RNA-interference (RNAi) is a homology-dependent innate immune response in eukaryotes, including insects, which results in degradation of the corresponding transcript following its recognition by a double-stranded RNA (dsRNA) that shares 100% sequence homology. In this study, six whitefly 'gut' genes were selected from an in silico-annotated transcriptome library constructed from the whitefly alimentary canal or 'gut' of the B biotype of B. tabaci, and tested for knock down efficacy, post-ingestion of dsRNAs that share 100% sequence homology to each respective gene target. Candidate genes were: Acetylcholine receptor subunit α, Alpha glucosidase 1, Aquaporin 1, Heat shock protein 70, Trehalase1, and Trehalose transporter1. The efficacy of RNAi knock down was further tested in a gene-specific functional bioassay, and mortality was recorded in 24 hr intervals, six days, post-treatment. Based on qPCR analysis, all six genes tested showed significantly reduced gene expression. Moderate-to-high whitefly mortality was associated with the down-regulation of osmoregulation, sugar metabolism and sugar transport-associated genes, demonstrating that whitefly survivability was linked with RNAi results. Silenced Acetylcholine receptor subunit α and Heat shock protein 70 genes showed an initial low whitefly mortality, however, following insecticide or high temperature treatments, respectively, significantly increased knockdown efficacy and death was observed, indicating enhanced post-knockdown sensitivity perhaps related to systemic silencing. The oral delivery of gut-specific dsRNAs, when combined with qPCR analysis of gene expression and a corresponding gene-specific bioassay that relates knockdown and mortality, offers a viable approach for functional genomics analysis and the discovery of prospective dsRNA biopesticide targets. The approach can

Multi-target drugs: the trend of drug research and development.

PubMed

Lu, Jin-Jian; Pan, Wei; Hu, Yuan-Jia; Wang, Yi-Tao

2012-01-01

Summarizing the status of drugs in the market and examining the trend of drug research and development is important in drug discovery. In this study, we compared the drug targets and the market sales of the new molecular entities approved by the U.S. Food and Drug Administration from January 2000 to December 2009. Two networks, namely, the target-target and drug-drug networks, have been set up using the network analysis tools. The multi-target drugs have much more potential, as shown by the network visualization and the market trends. We discussed the possible reasons and proposed the rational strategies for drug research and development in the future.

The translation research in a dental setting (TRiaDS) programme protocol

PubMed Central

2010-01-01

Background It is well documented that the translation of knowledge into clinical practice is a slow and haphazard process. This is no less true for dental healthcare than other types of healthcare. One common policy strategy to help promote knowledge translation is the production of clinical guidance, but it has been demonstrated that the simple publication of guidance is unlikely to optimise practice. Additional knowledge translation interventions have been shown to be effective, but effectiveness varies and much of this variation is unexplained. The need for researchers to move beyond single studies to develop a generalisable, theory based, knowledge translation framework has been identified. For dentistry in Scotland, the production of clinical guidance is the responsibility of the Scottish Dental Clinical Effectiveness Programme (SDCEP). TRiaDS (Translation Research in a Dental Setting) is a multidisciplinary research collaboration, embedded within the SDCEP guidance development process, which aims to establish a practical evaluative framework for the translation of guidance and to conduct and evaluate a programme of integrated, multi-disciplinary research to enhance the science of knowledge translation. Methods Set in General Dental Practice the TRiaDS programmatic evaluation employs a standardised process using optimal methods and theory. For each SDCEP guidance document a diagnostic analysis is undertaken alongside the guidance development process. Information is gathered about current dental care activities. Key recommendations and their required behaviours are identified and prioritised. Stakeholder questionnaires and interviews are used to identify and elicit salient beliefs regarding potential barriers and enablers towards the key recommendations and behaviours. Where possible routinely collected data are used to measure compliance with the guidance and to inform decisions about whether a knowledge translation intervention is required. Interventions are

Highly sensitive atomic based MW interferometry.

PubMed

Shylla, Dangka; Nyakang'o, Elijah Ogaro; Pandey, Kanhaiya

2018-06-06

We theoretically study a scheme to develop an atomic based micro-wave (MW) interferometry using the Rydberg states in Rb. Unlike the traditional MW interferometry, this scheme is not based upon the electrical circuits, hence the sensitivity of the phase and the amplitude/strength of the MW field is not limited by the Nyquist thermal noise. Further, this system has great advantage due to its much higher frequency range in comparision to the electrical circuit, ranging from radio frequency (RF), MW to terahertz regime. In addition, this is two orders of magnitude more sensitive to field strength as compared to the prior demonstrations on the MW electrometry using the Rydberg atomic states. Further, previously studied atomic systems are only sensitive to the field strength but not to the phase and hence this scheme provides a great opportunity to characterize the MW completely including the propagation direction and the wavefront. The atomic based MW interferometry is based upon a six-level loopy ladder system involving the Rydberg states in which two sub-systems interfere constructively or destructively depending upon the phase between the MW electric fields closing the loop. This work opens up a new field i.e. atomic based MW interferometry replacing the conventional electrical circuit in much superior fashion.

Mid-course multi-target tracking using continuous representation

NASA Technical Reports Server (NTRS)

Zak, Michail; Toomarian, Nikzad

1991-01-01

The thrust of this paper is to present a new approach to multi-target tracking for the mid-course stage of the Strategic Defense Initiative (SDI). This approach is based upon a continuum representation of a cluster of flying objects. We assume that the velocities of the flying objects can be embedded into a smooth velocity field. This assumption is based upon the impossibility of encounters in a high density cluster between the flying objects. Therefore, the problem is reduced to an identification of a moving continuum based upon consecutive time frame observations. In contradistinction to the previous approaches, here each target is considered as a center of a small continuous neighborhood subjected to a local-affine transformation, and therefore, the target trajectories do not mix. Obviously, their mixture in plane of sensor view is apparent. The approach is illustrated by an example.

Optimum Sensors Integration for Multi-Sensor Multi-Target Environment for Ballistic Missile Defense Applications

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

Imam, Neena; Barhen, Jacob; Glover, Charles Wayne

2012-01-01

Multi-sensor networks may face resource limitations in a dynamically evolving multiple target tracking scenario. It is necessary to task the sensors efficiently so that the overall system performance is maximized within the system constraints. The central sensor resource manager may control the sensors to meet objective functions that are formulated to meet system goals such as minimization of track loss, maximization of probability of target detection, and minimization of track error. This paper discusses the variety of techniques that may be utilized to optimize sensor performance for either near term gain or future reward over a longer time horizon.

Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

PubMed

Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

2018-02-01

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

SLAP deficiency decreases dsDNA autoantibody production

PubMed Central

Peterson, Lisa K.; Pennington, Luke F.; Shaw, Laura A.; Brown, Meredith; Treacy, Eric C.; Friend, Samantha F.; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V.; Dragone, Leonard L.

2014-01-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP−/− mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP−/− 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. PMID:24440645

SLAP deficiency decreases dsDNA autoantibody production.

PubMed

Peterson, Lisa K; Pennington, Luke F; Shaw, Laura A; Brown, Meredith; Treacy, Eric C; Friend, Samantha F; Hatlevik, Øyvind; Rubtsova, Kira; Rubtsov, Anatoly V; Dragone, Leonard L

2014-02-01

Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection. Copyright © 2013 Elsevier Inc. All rights reserved.

Biodegradation of furfural by Bacillus subtilis strain DS3.

PubMed

Zheng, Dan; Bao, Jianguo; Lu, Jueming; Lv, Quanxi

2015-07-01

An aerobic bacterial strain DS3, capable of growing on furfural as sole carbon source, was isolated from actived sludge of wastewater treatment plant in a diosgenin factory after enrichment. Based on morphological physiological tests as well as 16SrDNA sequence and Biolog analyses it was identified as Bacillus subtilis. The study revealed that strain DS3 utilized furfural, as analyzed by high-performance liquid chromatography (HPLC). Under following conditions: pH 8.0, temperature 35 degrees C, 150 rpm and 10% inoculum, strain DS3 showed 31.2% furfural degradation. Furthermore, DS3 strain was found to tolerate furfural concentration as high as 6000 mg(-1). The ability of Bacillus subtilis strain DS3 to degrade furfural has been demonstrated for the first time in the present study.

Research on target information optics communications transmission characteristic and performance in multi-screens testing system

NASA Astrophysics Data System (ADS)

Li, Hanshan

2016-04-01

To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

22 CFR 62.12 - Control of Forms DS-2019.

Code of Federal Regulations, 2010 CFR

2010-04-01

... transfer; (4) Replace a lost or stolen Form DS-2019; (5) Facilitate entry of an exchange visitor's alien spouse or minor unmarried children into the United States separately; (6) Facilitate re-entry of an... Form DS-2019. Issue the Form DS-2019 only so as to: (1) Facilitate the entry of a new participant of...

22 CFR 62.12 - Control of Forms DS-2019.

Code of Federal Regulations, 2013 CFR

2013-04-01

... transfer; (4) Replace a lost or stolen Form DS-2019; (5) Facilitate entry of an exchange visitor's alien spouse or minor unmarried children into the United States separately; (6) Facilitate re-entry of an... Form DS-2019. Issue the Form DS-2019 only so as to: (1) Facilitate the entry of a new participant of...

22 CFR 62.12 - Control of Forms DS-2019.

Code of Federal Regulations, 2011 CFR

2011-04-01

... transfer; (4) Replace a lost or stolen Form DS-2019; (5) Facilitate entry of an exchange visitor's alien spouse or minor unmarried children into the United States separately; (6) Facilitate re-entry of an... Form DS-2019. Issue the Form DS-2019 only so as to: (1) Facilitate the entry of a new participant of...

22 CFR 62.12 - Control of Forms DS-2019.

Code of Federal Regulations, 2014 CFR

2014-04-01

... transfer; (4) Replace a lost or stolen Form DS-2019; (5) Facilitate entry of an exchange visitor's alien spouse or minor unmarried children into the United States separately; (6) Facilitate re-entry of an... Form DS-2019. Issue the Form DS-2019 only so as to: (1) Facilitate the entry of a new participant of...

22 CFR 62.12 - Control of Forms DS-2019.

Code of Federal Regulations, 2012 CFR

2012-04-01

... transfer; (4) Replace a lost or stolen Form DS-2019; (5) Facilitate entry of an exchange visitor's alien spouse or minor unmarried children into the United States separately; (6) Facilitate re-entry of an... Form DS-2019. Issue the Form DS-2019 only so as to: (1) Facilitate the entry of a new participant of...

Evaluation of a new automated enzyme fluoroimmunoassay using recombinant plasmid dsDNA for the detection of anti-dsDNA antibodies in SLE.

PubMed

Villalta, D; Bizzaro, N; Corazza, D; Tozzoli, R; Tonutti, E

2002-01-01

ELISA methods to detect anti-double-stranded DNA (anti-dsDNA) antibodies are highly sensitive, but are less specific for the diagnosis of SLE than the immunofluorescence test on Crithidia luciliae (CLIFT) and the Farr assay because they also detect low-avidity antibodies. This study evaluated the specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of a new automated fluoroimmunoassay (EliA dsDNA; Pharmacia, Freiburg, Germany). We compared the results with those obtained using a commercial CLIFT and an in-house anti-dsDNA IgG ELISA method, and verified its putative ability to detect only high-avidity anti-dsDNA antibodies. Sera from 100 SLE patients and 120 controls were studied. The control group included 20 healthy donors, 70 patients with other rheumatic diseases (32 systemic sclerosis (SSc); 18 primary Sjögren syndrome (pSS), 20 rheumatoid arthritis (RA)), and 30 patients with various infectious diseases (ID). Anti-dsDNA avidity was estimated using an ELISA method based upon the law of mass action, and a simplified Scatchard plot analysis for data elaboration; the apparent affinity constant (Kaa) was calculated and expressed as arbitrary units (L/U). Sensitivity, specificity, PPV, and NPV for SLE were 64%, 95.8%, 93.8% and 72.7%, respectively, for the EliA anti-dsDNA assay; 55%, 99.2%, 98.5%, and 68.8%, respectively, for the CLIFT; and 64%, 93.3%, 90.6%, and 72.3%, respectively, for the in-house ELISA. Although EliA anti-dsDNA was positive mainly in SLE patients with high- (Kaa>80 L/U) and intermediate- (Kaa 30-80 L/U) avidity antibodies (45.3% and 49.9%, respectively), it was also positive in five (7.8%) SLE patients with low-avidity anti-dsDNA antibodies, and five controls (three SSc, one pSS, and one ID) (mean Kaa = 16.4 +/- 9.04 L/U). In conclusion, EliA anti-dsDNA assay showed a higher sensitivity than the CLIFT, and a good specificity and PPV for SLE. Its putative ability to detect only high-avidity anti-ds

An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer.

PubMed

Qi, Lihua; Song, Yangyang; Chan, Tim Hon Man; Yang, Henry; Lin, Chi Ho; Tay, Daryl Jin Tai; Hong, HuiQi; Tang, Sze Jing; Tan, Kar Tong; Huang, Xi Xiao; Lin, Jaymie Siqi; Ng, Vanessa Hui En; Maury, Julien Jean Pierre; Tenen, Daniel G; Chen, Leilei

2017-10-13

Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3' untranslated regions (3'UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3'UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3'UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3'UTR to repress its expression level. In sum, our study unveils that the extensive 3'UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer

PubMed Central

Qi, Lihua; Song, Yangyang; Chan, Tim Hon Man; Yang, Henry; Lin, Chi Ho; Tay, Daryl Jin Tai; Hong, HuiQi; Tang, Sze Jing; Tan, Kar Tong; Huang, Xi Xiao; Lin, Jaymie Siqi; Ng, Vanessa Hui En; Maury, Julien Jean Pierre

2017-01-01

Abstract Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3′ untranslated regions (3′UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3′UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3′UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3′UTR to repress its expression level. In sum, our study unveils that the extensive 3′UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer. PMID:28985428

SU-G-BRA-17: Tracking Multiple Targets with Independent Motion in Real-Time Using a Multi-Leaf Collimator

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

Ge, Y; Keall, P; Poulsen, P

Purpose: Multiple targets with large intrafraction independent motion are often involved in advanced prostate, lung, abdominal, and head and neck cancer radiotherapy. Current standard of care treats these with the originally planned fields, jeopardizing the treatment outcomes. A real-time multi-leaf collimator (MLC) tracking method has been developed to address this problem for the first time. This study evaluates the geometric uncertainty of the multi-target tracking method. Methods: Four treatment scenarios are simulated based on a prostate IMAT plan to treat a moving prostate target and static pelvic node target: 1) real-time multi-target MLC tracking; 2) real-time prostate-only MLC tracking; 3)more » correcting for prostate interfraction motion at setup only; and 4) no motion correction. The geometric uncertainty of the treatment is assessed by the sum of the erroneously underexposed target area and overexposed healthy tissue areas for each individual target. Two patient-measured prostate trajectories of average 2 and 5 mm motion magnitude are used for simulations. Results: Real-time multi-target tracking accumulates the least uncertainty overall. As expected, it covers the static nodes similarly well as no motion correction treatment and covers the moving prostate similarly well as the real-time prostate-only tracking. Multi-target tracking reduces >90% of uncertainty for the static nodal target compared to the real-time prostate-only tracking or interfraction motion correction. For prostate target, depending on the motion trajectory which affects the uncertainty due to leaf-fitting, multi-target tracking may or may not perform better than correcting for interfraction prostate motion by shifting patient at setup, but it reduces ∼50% of uncertainty compared to no motion correction. Conclusion: The developed real-time multi-target MLC tracking can adapt for the independently moving targets better than other available treatment adaptations. This will enable

Multi-MW K-Band Harmonic Multiplier: RF Source For High-Gradient Accelerator R & D

NASA Astrophysics Data System (ADS)

Solyak, N. A.; Yakovlev, V. P.; Kazakov, S. Yu.; Hirshfield, J. L.

2009-01-01

A preliminary design is presented for a two-cavity harmonic multiplier, intended as a high-power RF source for use in experiments aimed at developing high-gradient structures for a future collider. The harmonic multiplier is to produce power at selected frequencies in K-band (18-26.5 GHz) using as an RF driver an XK-5 S-band klystron (2.856 GHz). The device is to be built with a TE111 rotating mode input cavity and interchangeable output cavities running in the TEn11 rotating mode, with n = 7,8,9 at 19.992, 22.848, and 25.704 GHz. An example for a 7th harmonic multiplier is described, using a 250 kV, 20 A injected laminar electron beam; with 10 MW of S-band drive power, 4.7 MW of 20-GHz output power is predicted. Details are described of the magnetic circuit, cavities, and output coupler.

Measurement of Bs0 and Ds- Meson Lifetimes

NASA Astrophysics Data System (ADS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Ajaltouni, Z.; Akar, S.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Arnau Romeu, J.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Baszczyk, M.; Batozskaya, V.; Batsukh, B.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M.-O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Braun, S.; Britton, T.; Brodzicka, J.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D. H.; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Castillo Garcia, L.; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Chen, S.; Cheung, S.-F.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Costa Sobral, C. M.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Dembinski, H.-P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dijkstra, H.; Dordei, F.; Dorigo, M.; Dosil Suárez, A.; Dovbnya, A.; Dreimanis, K.; Dufour, L.; Dujany, G.; Dungs, K.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Déléage, N.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fay, R.; Fazzini, D.; Ferguson, D.; Fernandez, G.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Franco Lima, V.; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Färber, C.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; García Pardiñas, J.; Garra Tico, J.; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gianı, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Griffith, P.; Grillo, L.; Gruberg Cazon, B. R.; Grünberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Göbel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hatch, M.; He, J.; Head, T.; Heister, A.; Hennessy, K.; Henrard, P.; Henry, L.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, H.; Huard, Z.-C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; Jiang, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Komarov, I.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozachuk, A.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Leflat, A.; Lefrançois, J.; Lefèvre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, T.; Li, Y.; Li, Z.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Liu, X.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Minard, M.-N.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mulder, M.; Mussini, M.; Müller, D.; Müller, J.; Müller, K.; Müller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, T. D.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Poli Lener, M.; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Popovici, B.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, C.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Rodriguez Perez, P.; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Gonzalo, D.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Sarti, A.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubert, K.; Schubiger, M.; Schune, M.-H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Silva Coutinho, R.; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, E.; Smith, I. T.; Smith, J.; Smith, M.; Soares Lavra, l.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stevens, H.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; Thomas, E.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Viana Barbosa, J. V.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voß, C.; de Vries, J. A.; Vázquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wang, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Williams, T.; Wilson, F. F.; Wimberley, J.; Winn, M. A.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yang, Z.; Yao, Y.; Yin, H.; Yu, J.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhang, L.; Zhang, Y.; Zhelezov, A.; Zheng, Y.; Zhu, X.; Zhukov, V.; Zucchelli, S.; LHCb Collaboration

2017-09-01

We report on a measurement of the flavor-specific Bs0 lifetime and of the Ds- lifetime using proton-proton collisions at center-of-mass energies of 7 and 8 TeV, collected by the LHCb experiment and corresponding to 3.0 fb-1 of integrated luminosity. Approximately 407 000 Bs0→Ds(*)-μ+νμ decays are partially reconstructed in the K+K-π-μ+ final state. The Bs0 and Ds- natural widths are determined using, as a reference, kinematically similar B0→D(*)-μ+νμ decays reconstructed in the same final state. The resulting differences between widths of Bs0 and B0 mesons and of Ds- and D- mesons are ΔΓ(B )=-0.0115 ±0.0053 (stat ) ±0.0041 (syst ) ps-1 and ΔΓ(D )=1.0131 ±0.0117 (stat ) ±0.0065 (syst ) ps-1, respectively. Combined with the known B0 and D- lifetimes, these yield the flavor-specific Bs0 lifetime, τBs 0 fs =1.547 ±0.013 (stat ) ±0.010 (syst ) ±0.004 (τB) ps and the Ds- lifetime, τDs-=0.5064 ±0.0030 (stat ) ±0.0017 (syst ) ±0.0017 (τD) ps . The last uncertainties originate from the limited knowledge of the B0 and D- lifetimes. The results improve upon current determinations.

Confidence level estimation in multi-target classification problems

NASA Astrophysics Data System (ADS)

Chang, Shi; Isaacs, Jason; Fu, Bo; Shin, Jaejeong; Zhu, Pingping; Ferrari, Silvia

2018-04-01

This paper presents an approach for estimating the confidence level in automatic multi-target classification performed by an imaging sensor on an unmanned vehicle. An automatic target recognition algorithm comprised of a deep convolutional neural network in series with a support vector machine classifier detects and classifies targets based on the image matrix. The joint posterior probability mass function of target class, features, and classification estimates is learned from labeled data, and recursively updated as additional images become available. Based on the learned joint probability mass function, the approach presented in this paper predicts the expected confidence level of future target classifications, prior to obtaining new images. The proposed approach is tested with a set of simulated sonar image data. The numerical results show that the estimated confidence level provides a close approximation to the actual confidence level value determined a posteriori, i.e. after the new image is obtained by the on-board sensor. Therefore, the expected confidence level function presented in this paper can be used to adaptively plan the path of the unmanned vehicle so as to optimize the expected confidence levels and ensure that all targets are classified with satisfactory confidence after the path is executed.

Analysis, optimization, and implementation of a hybrid DS/FFH spread-spectrum technique for smart grid communications

DOE PAGES

Olama, Mohammed M.; Ma, Xiao; Killough, Stephen M.; ...

2015-03-12

In recent years, there has been great interest in using hybrid spread-spectrum (HSS) techniques for commercial applications, particularly in the Smart Grid, in addition to their inherent uses in military communications. This is because HSS can accommodate high data rates with high link integrity, even in the presence of significant multipath effects and interfering signals. A highly useful form of this transmission technique for many types of command, control, and sensing applications is the specific code-related combination of standard direct sequence modulation with fast frequency hopping, denoted hybrid DS/FFH, wherein multiple frequency hops occur within a single data-bit time. Inmore » this paper, error-probability analyses are performed for a hybrid DS/FFH system over standard Gaussian and fading-type channels, progressively including the effects from wide- and partial-band jamming, multi-user interference, and varying degrees of Rayleigh and Rician fading. In addition, an optimization approach is formulated that minimizes the bit-error performance of a hybrid DS/FFH communication system and solves for the resulting system design parameters. The optimization objective function is non-convex and can be solved by applying the Karush-Kuhn-Tucker conditions. We also present our efforts toward exploring the design, implementation, and evaluation of a hybrid DS/FFH radio transceiver using a single FPGA. Numerical and experimental results are presented under widely varying design parameters to demonstrate the adaptability of the waveform for varied harsh smart grid RF signal environments.« less

Nucleic acid encoding DS-CAM proteins and products related thereto

DOEpatents

Korenberg, Julie R.

2005-11-01

In accordance with the present invention, there are provided Down Syndrome-Cell Adhesion Molecule (DS-CAM) proteins. Nucleic acid sequences encoding such proteins and assays employing same are also disclosed. The invention DS-CAM proteins can be employed in a variety of ways, for example, for the production of anti-DS-CAM antibodies thereto, in therapeutic compositions and methods employing such proteins and/or antibodies. DS-CAM proteins are also useful in bioassays to identify agonists and antagonists thereto.

Light-induced flickering of DsRed provides evidence for distinct and interconvertible fluorescent states.

PubMed Central

Malvezzi-Campeggi, F; Jahnz, M; Heinze, K G; Dittrich, P; Schwille, P

2001-01-01

Green fluorescent protein (GFP) from jellyfish Aequorea victoria, the powerful genetically encoded tag presently available in a variety of mutants featuring blue to yellow emission, has found a red-emitting counterpart. The recently cloned red fluorescent protein DsRed, isolated from Discosoma corals (), with its emission maximum at 583 nm, appears to be the long awaited tool for multi-color applications in fluorescence-based biological research. Studying the emission dynamics of DsRed by fluorescence correlation spectroscopy (FCS), it can be verified that this protein exhibits strong light-dependent flickering similar to what is observed in several yellow-shifted mutants of GFP. FCS data recorded at different intensities and excitation wavelengths suggest that DsRed appears under equilibrated conditions in at minimum three interconvertible states, apparently fluorescent with different excitation and emission properties. Light absorption induces transitions and/or cycling between these states on time scales of several tens to several hundreds of microseconds, dependent on excitation intensity. With increasing intensity, the emission maximum of the static fluorescence continuously shifts to the red, implying that at least one state emitting at longer wavelength is preferably populated at higher light levels. In close resemblance to GFP, this light-induced dynamic behavior implies that the chromophore is subject to conformational rearrangements upon population of the excited state. PMID:11509387

Diclofenac sodium (DS) loaded bioerodible polymer based constructs

NASA Astrophysics Data System (ADS)

Piras, M.; Chiellini, F.; Nikkola, L.; Ashammakhi, N.; Chiellini, E.

2008-02-01

Pain is a prevalent problem that can raise morbidity of patients. Pain killer releasing biodegradable materials have been developed by using different techniques and biomaterials. The objective of the current study is to evaluate the use of a new bioerodible polymer for release of diclofenac sodium (DS). 1-butanol hemiester poly(maleic anhydride-alt-2-methoxyethyl vinyl ether) (PAM14) was prepared in the university of Pisa and selected as polymer of choice for the study. Polymer solutions of 5-10% (in ethanol or in acetic acid) were prepared, half of them containing 2% DS. The solutions were then electrospun to produce nanomats that were subsequently characterized using SEM. Fiber diameter was 160 nm 1 μm. Increasing polymer concentration increased the size of the fibers but reduced the number of beads (with or without DS). In the specimens obtained from acetic acid solution, the addition of DS resulted in a reduction in fiber diameter and an increase in the inter-bead distance. Corresponding ethanol solutions gave more homogeneous specimens than did acetic acid, having a lower number of beads. With the addition of DS a reduction in fiber diameter was observed for the acetic acid specimens. However, in ethanol, adding DS resulted in increased fiber diameter. Accordingly, it can be concluded that it is feasible to develop electrospun diclofenac releasing bioerodible nanostructures that have potential use in pain management. Their further evaluation is however, needed both in vitro and in vivo.

75 FR 39322 - 30-Day Notice of Proposed Information Collection: Retail Price Schedule, DS-2020 Parts 1-4, DS...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-08

.... Originating Office: Bureau of Administration Office of Allowances (A/OPR/ALS). Form Number: DS-2020, DS-2020I...: [email protected] . Mail (paper, disk, or CD-ROM submissions): Office of Allowances (A/OPR/ALS), Room... Delivery or Courier: Office of Allowances (A/OPR/ ALS), Room L314, Department of State, 2401 E Street, NW...

Dicer uses distinct modules for recognizing dsRNA termini.

PubMed

Sinha, Niladri K; Iwasa, Janet; Shen, Peter S; Bass, Brenda L

2018-01-19

Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo-electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate-dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Calibration Method for IATS and Application in Multi-Target Monitoring Using Coded Targets

NASA Astrophysics Data System (ADS)

Zhou, Yueyin; Wagner, Andreas; Wunderlich, Thomas; Wasmeier, Peter

2017-06-01

The technique of Image Assisted Total Stations (IATS) has been studied for over ten years and is composed of two major parts: one is the calibration procedure which combines the relationship between the camera system and the theodolite system; the other is the automatic target detection on the image by various methods of photogrammetry or computer vision. Several calibration methods have been developed, mostly using prototypes with an add-on camera rigidly mounted on the total station. However, these prototypes are not commercially available. This paper proposes a calibration method based on Leica MS50 which has two built-in cameras each with a resolution of 2560 × 1920 px: an overview camera and a telescope (on-axis) camera. Our work in this paper is based on the on-axis camera which uses the 30-times magnification of the telescope. The calibration consists of 7 parameters to estimate. We use coded targets, which are common tools in photogrammetry for orientation, to detect different targets in IATS images instead of prisms and traditional ATR functions. We test and verify the efficiency and stability of this monitoring method with multi-target.

Helical Structure Determines Different Susceptibilities of dsDNA, dsRNA, and tsDNA to Counterion-Induced Condensation

PubMed Central

Kornyshev, Alexei A.; Leikin, Sergey

2013-01-01

Recent studies of counterion-induced condensation of nucleic acid helices into aggregates produced several puzzling observations. For instance, trivalent cobalt hexamine ions condensed double-stranded (ds) DNA oligomers but not their more highly charged dsRNA counterparts. Divalent alkaline earth metal ions condensed triple-stranded (ts) DNA oligomers but not dsDNA. Here we show that these counterintuitive experimental results can be rationalized within the electrostatic zipper model of interactions between molecules with helical charge motifs. We report statistical mechanical calculations that reveal dramatic and nontrivial interplay between the effects of helical structure and thermal fluctuations on electrostatic interaction between oligomeric nucleic acids. Combining predictions for oligomeric and much longer helices, we also interpret recent experimental studies of the role of counterion charge, structure, and chemistry. We argue that an electrostatic zipper attraction might be a major or even dominant force in nucleic acid condensation. PMID:23663846

Development of a Multi-Target Contingency Management Intervention for HIV Positive Substance Users.

PubMed

Stitzer, Maxine; Calsyn, Donald; Matheson, Timothy; Sorensen, James; Gooden, Lauren; Metsch, Lisa

2017-01-01

Contingency management (CM) interventions generally target a single behavior such as attendance or drug use. However, disease outcomes are mediated by complex chains of both healthy and interfering behaviors enacted over extended periods of time. This paper describes a novel multi-target contingency management (CM) program developed for use with HIV positive substance users enrolled in a CTN multi-site study (0049 Project HOPE). Participants were randomly assigned to usual care (referral to health care and SUD treatment) or 6-months strength-based patient navigation interventions with (PN+CM) or without (PN only) the CM program. Primary outcome of the trial was viral load suppression at 12-months post-randomization. Up to $1160 could be earned over 6 months under escalating schedules of reinforcement. Earnings were divided among eight CM targets; two PN-related (PN visits; paperwork completion; 26% of possible earnings), four health-related (HIV care visits, lab blood draw visits, medication check, viral load suppression; 47% of possible earnings) and two drug-use abatement (treatment entry; submission of drug negative UAs; 27% of earnings). The paper describes rationale for selection of targets, pay amounts and pay schedules. The CM program was compatible with and fully integrated into the PN intervention. The study design will allow comparison of behavioral and health outcomes for participants receiving PN with and without CM; results will inform future multi-target CM development. Copyright © 2016 Elsevier Inc. All rights reserved.

The application and research of the multi-receiving telescopes technology in laser ranging to space targets

NASA Astrophysics Data System (ADS)

Wu, Zhibo; Zhang, Haifeng; Zhang, Zhongping; Deng, Huarong; Li, Pu; Meng, Wendong; Cheng, Zhien; Shen, Lurun; Tang, Zhenhong

2014-11-01

Laser ranging technology can directly measure the distance between space targets and ground stations with the highest measurement precision and will play an irreplaceable role in orbit check and calibrating microwave measurement system. The precise orbit determination and accurate catalogue of space targets can also be realized by laser ranging with multi-stations. Among space targets, most of ones are inactive targets and space debris, which should be paid the great attentions for the safety of active spacecrafts. Because of laser diffuse reflection from the surface of targets, laser ranging to space debris has the characteristics of wide coverage and weak strength of laser echoes, even though the powerful laser system is applied. In order to increase the receiving ability of laser echoes, the large aperture telescope should be adopted. As well known, some disadvantages for one set of large aperture telescope, technical development difficulty and system running and maintenance complexity, will limit its flexible applications. The multi-receiving telescopes technology in laser ranging to space targets is put forward to realize the equivalent receiving ability produced by one larger aperture telescope by way of using multi-receiving telescopes, with the advantages of flexibility and maintenance. The theoretical analysis of the feasibility and key technologies of multi-receiving telescopes technology in laser ranging to space targets are presented in this paper. The experimental measurement system based on the 60cm SLR system and 1.56m astronomical telescopes with a distance of about 50m is established to provide the platform for researching on the multi-receiving telescopes technology. The laser ranging experiments to satellites equipped with retro-reflectors are successfully performed by using the above experimental system and verify the technical feasibility to increase the ability of echo detection. And the multi-receiving telescopes technology will become a

A Multi-targeted Approach to Suppress Tumor-Promoting Inflammation

PubMed Central

Samadi, Abbas K.; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Bishayee, Anupam; Lokeshwar, Bal L.; Grue, Brendan; Panis, Carolina; Boosani, Chandra S.; Poudyal, Deepak; Stafforini, Diana M.; Bhakta, Dipita; Niccolai, Elena; Guha, Gunjan; Rupasinghe, H.P. Vasantha; Fujii, Hiromasa; Honoki, Kanya; Mehta, Kapil; Aquilano, Katia; Lowe, Leroy; Hofseth, Lorne J.; Ricciardiello, Luigi; Ciriolo, Maria Rosa; Singh, Neetu; Whelan, Richard L.; Chaturvedi, Rupesh; Ashraf, S. Salman; Kumara, HMC Shantha; Nowsheen, Somaira; Mohammed, Sulma I.; Helferich, William G.; Yang, Xujuan

2015-01-01

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-kappaB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes. PMID:25951989

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

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

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

The R&D progress of 4 MW EAST-NBI high current ion source.

PubMed

Xie, Yahong; Hu, Chundong; Liu, Sheng; Xu, Yongjian; Liang, Lizhen; Xie, Yuanlai; Sheng, Peng; Jiang, Caichao; Liu, Zhimin

2014-02-01

A high current ion source, which consists of the multi-cusp bucket plasma generator and tetrode accelerator with multi-slot apertures, is developed and tested for the Experimental Advanced Superconducting Tokamak neutral beam injector. Three ion sources are tested on the test bed with arc power of 80 kW, beam voltage of 80 keV, and beam power of 4 MW. The arc regulation technology with Langmuir probes is employed for the long pulse operation of ion source, and the long pulse beam of 50 keV @ 15.5 A @ 100 s and 80 keV @ 52A @ 1s are extracted, respectively.

Accurate multi-robot targeting for keyhole neurosurgery based on external sensor monitoring.

PubMed

Comparetti, Mirko Daniele; Vaccarella, Alberto; Dyagilev, Ilya; Shoham, Moshe; Ferrigno, Giancarlo; De Momi, Elena

2012-05-01

Robotics has recently been introduced in surgery to improve intervention accuracy, to reduce invasiveness and to allow new surgical procedures. In this framework, the ROBOCAST system is an optically surveyed multi-robot chain aimed at enhancing the accuracy of surgical probe insertion during keyhole neurosurgery procedures. The system encompasses three robots, connected as a multiple kinematic chain (serial and parallel), totalling 13 degrees of freedom, and it is used to automatically align the probe onto a desired planned trajectory. The probe is then inserted in the brain, towards the planned target, by means of a haptic interface. This paper presents a new iterative targeting approach to be used in surgical robotic navigation, where the multi-robot chain is used to align the surgical probe to the planned pose, and an external sensor is used to decrease the alignment errors. The iterative targeting was tested in an operating room environment using a skull phantom, and the targets were selected on magnetic resonance images. The proposed targeting procedure allows about 0.3 mm to be obtained as the residual median Euclidean distance between the planned and the desired targets, thus satisfying the surgical accuracy requirements (1 mm), due to the resolution of the diffused medical images. The performances proved to be independent of the robot optical sensor calibration accuracy.

Excited delirium syndrome (ExDS): treatment options and considerations.

PubMed

Vilke, Gary M; Bozeman, William P; Dawes, Donald M; Demers, Gerard; Wilson, Michael P

2012-04-01

The term Excited Delirium Syndrome (ExDS) has traditionally been used in the forensic literature to describe findings in a subgroup of patients with delirium who suffered lethal consequences from their untreated severe agitation.(1-5) Excited delirium syndrome, also known as agitated delirium, is generally defined as altered mental status and combativeness or aggressiveness. Although the exact signs and symptoms are difficult to define precisely, clinical findings often include many of the following: tolerance to significant pain, rapid breathing, sweating, severe agitation, elevated temperature, delirium, non-compliance or poor awareness to direction from police or medical personnel, lack of fatiguing, unusual or superhuman strength, and inappropriate clothing for the current environment. It has become increasingly recognized that individuals displaying ExDS are at high risk for sudden death, and ExDS therefore represents a true medical emergency. Recently the American College of Emergency Physicians (ACEP) published the findings of a white paper on the topic of ExDS to better find consensus on the issues of definition, diagnosis, and treatment.(6) In so doing, ACEP joined the National Association of Medical Examiners (NAME) in recognizing ExDS as a medical condition. For both paramedics and physicians, the difficulty in diagnosing the underlying cause of ExDS in an individual patient is that the presenting clinical signs and symptoms of ExDS can be produced by a wide variety of clinical disease processes. For example, agitation, combativeness, and altered mental status can be produced by hypoglycemia, thyroid storm, certain kinds of seizures, and these conditions can be difficult to distinguish from those produced by cocaine or methamphetamine intoxication.(7) Prehospital personnel are generally not expected to differentiate between the multiple possible causes of the patient's presentation, but rather simply to recognize that the patient has a medical emergency

KiDS-i-800: Comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-04-01

We present a weak gravitational lensing analysis of 815deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS dataset (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4%. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5% when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

Highly efficient delivery of siRNA to a heart transplant model by a novel cell penetrating peptide-dsRNA binding domain.

PubMed

Li, Hua; Zheng, Xiangtao; Koren, Viktoria; Vashist, Yogesh Kumar; Tsui, Tung Yu

2014-07-20

Small interfering RNAs (siRNAs) delivery remains a bottleneck for RNA interference (RNAi) - based therapies in the clinic. In the present study, a fusion protein with two cell-penetrating peptides (CPP), Hph1-Hph1, and a double-stranded RNA binding domain (dsRBD), was constructed for the siRNA delivery: dsRBD was designed to bind siRNA, and CPP would subsequently transport the dsRBD/siRNA complex into cells. We assessed the efficiency of the fusion protein, Hph1-Hph1-dsRBD, as a siRNA carrier. Calcium-condensed effects were assessed on GAPDH and green fluorescent protein (GFP) genes by western blot, real time polymerase chain reaction (RT-PCR), and flow cytometry analysis in vitro. Evaluations were also made in an in vivo heart transplantation model. The results demonstrated that the fusion protein, Hph1-Hph1-dsRBD, is highly efficient at delivering siRNA in vitro, and exhibits efficiency on GAPDH and GFP genes similar to or greater than lipofectamine. Interestingly, the calcium-condensed effects dramatically enhanced cellular uptake of the protein-siRNA complex. In vivo, Hph1-Hph1-dsRBD transferred and distributed ^ targeted siRNA throughout the whole mouse heart graft. Together, these results indicate that Hph1-Hph1-dsRBD has potential as an siRNA carrier for applications in the clinic or in biomedical research. Copyright © 2014 Elsevier B.V. All rights reserved.

A novel pathway to detect and cope with exogenous dsDNA.

PubMed

Kobayashi, Shouhei; Haraguchi, Tokuko

2015-01-01

How a living cell responds to exogenous materials is one of the fundamental questions in the life sciences. In particular, understanding the mechanisms by which a cell recognizes exogenous double-stranded DNA (dsDNA) is important for immunology research because it will facilitate the control of pathogen infections that entail the presence of exogenous dsDNA in the cytoplasm of host cells. Several cytosolic dsDNA sensor proteins that trigger innate immune responses have been identified and the downstream signaling pathways have been investigated. However, the events that occur at the site of exogenous dsDNA when it is exposed to the cytosol of the host cell remain unknown. Using dsDNA-coated polystyrene beads incorporated into living cells, we recently found that barrier-to-autointegration factor (BAF) binds to the exogenous dsDNA immediately after its appearance in the cytosol and plays a role in DNA avoidance of autophagy. Our findings reveal a novel pathway in which BAF plays a key role in the detection of and response to exogenous dsDNA.

SU-E-T-214: Intensity Modulated Proton Therapy (IMPT) Based On Passively Scattered Protons and Multi-Leaf Collimation: Prototype TPS and Dosimetry Study

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

Sanchez-Parcerisa, D; Carabe-Fernandez, A

2014-06-01

Purpose. Intensity-modulated proton therapy is usually implemented with multi-field optimization of pencil-beam scanning (PBS) proton fields. However, at the view of the experience with photon-IMRT, proton facilities equipped with double-scattering (DS) delivery and multi-leaf collimation (MLC) could produce highly conformal dose distributions (and possibly eliminate the need for patient-specific compensators) with a clever use of their MLC field shaping, provided that an optimal inverse TPS is developed. Methods. A prototype TPS was developed in MATLAB. The dose calculation process was based on a fluence-dose algorithm on an adaptive divergent grid. A database of dose kernels was precalculated in order tomore » allow for fast variations of the field range and modulation during optimization. The inverse planning process was based on the adaptive simulated annealing approach, with direct aperture optimization of the MLC leaves. A dosimetry study was performed on a phantom formed by three concentrical semicylinders separated by 5 mm, of which the inner-most and outer-most were regarded as organs at risk (OARs), and the middle one as the PTV. We chose a concave target (which is not treatable with conventional DS fields) to show the potential of our technique. The optimizer was configured to minimize the mean dose to the OARs while keeping a good coverage of the target. Results. The plan produced by the prototype TPS achieved a conformity index of 1.34, with the mean doses to the OARs below 78% of the prescribed dose. This Result is hardly achievable with traditional conformal DS technique with compensators, and it compares to what can be obtained with PBS. Conclusion. It is certainly feasible to produce IMPT fields with MLC passive scattering fields. With a fully developed treatment planning system, the produced plans can be superior to traditional DS plans in terms of plan conformity and dose to organs at risk.« less

DsRNA as a stimulator of cell pacemaker activity

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

Airapetyan, S.N.; Zakharyan, R.A.; Rychkov, G.E.

1986-03-01

The authors study the action of double-stranded RNAs (dsRNA) on the characteristics of neuron pacemaker activity which permits prediction of the character of action of dsRNA on the pacemaker activity of cells and organs, and takes the investigators closer to an understanding of the membrane mechanisms underlying the action of dsRNA on the cell. The methods for isolating and fractionating dsRNA from yeasts and the intracellular recording of the electrical activity of the snail giant neuron have been described by the authors earlier. The authors determined the dependence of Ca/sup 2 +/ entry upon dsRNA concentration using the isotope /supmore » 45/Ca. Preweighed ganglia were incubated five each for an hour in 2 ml Ringer's solution containing dsRNA and 5 microliters /sup 45/CaCl/sub 2/ of 12.5 mCi activity. After incubation, the ganglia were rinsed three times for 8 min each time in normal Ringers solution. The washed ganglia were dissolved for one day in KOH. The amount of isotope entering was counted using Brav's scintillator and an RGT counter tuned to the /sup 45/Ca isotope. The physiological saline used for the isolated ganglion contained 85 mmole NaCl, 4 mmole KCl, 8 mmole CaCl/sub 2/, 10 mmole MgCl/sub 2/, 10 mmole Tris-HCl, and 5 mmole glucose.« less

Multi-Maneuver Clohessy-Wiltshire Targeting

NASA Technical Reports Server (NTRS)

Dannemiller, David P.

2011-01-01

Orbital rendezvous involves execution of a sequence of maneuvers by a chaser vehicle to bring the chaser to a desired state relative to a target vehicle while meeting intermediate and final relative constraints. Intermediate and final relative constraints are necessary to meet a multitude of requirements such as to control approach direction, ensure relative position is adequate for operation of space-to-space communication systems and relative sensors, provide fail-safe trajectory features, and provide contingency hold points. The effect of maneuvers on constraints is often coupled, so the maneuvers must be solved for as a set. For example, maneuvers that affect orbital energy change both the chaser's height and downrange position relative to the target vehicle. Rendezvous designers use experience and rules-of-thumb to design a sequence of maneuvers and constraints. A non-iterative method is presented for targeting a rendezvous scenario that includes a sequence of maneuvers and relative constraints. This method is referred to as Multi-Maneuver Clohessy-Wiltshire Targeting (MM_CW_TGT). When a single maneuver is targeted to a single relative position, the classic CW targeting solution is obtained. The MM_CW_TGT method involves manipulation of the CW state transition matrix to form a linear system. As a starting point for forming the algorithm, the effects of a series of impulsive maneuvers on the state are derived. Simple and moderately complex examples are used to demonstrate the pattern of the resulting linear system. The general form of the pattern results in an algorithm for formation of the linear system. The resulting linear system relates the effect of maneuver components and initial conditions on relative constraints specified by the rendezvous designer. Solution of the linear system includes the straight-forward inverse of a square matrix. Inversion of the square matrix is assured if the designer poses a controllable scenario - a scenario where the the

Urine Multi-drug Screening with GC-MS or LC-MS-MS Using SALLE-hybrid PPT/SPE.

PubMed

Lee, Junhui; Park, Jiwon; Go, Ahra; Moon, Heesung; Kim, Sujin; Jung, Sohee; Jeong, Wonjoon; Chung, Heesun

2018-05-14

To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC-MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid-liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC-MS-MS. GC-MS analysis was performed as unknown drug screen and LC-MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC-MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC-MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC-MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.

Seedling lethality in Nicotiana plumbaginifolia conferred by Ds transposable element insertion into a plant-specific gene.

PubMed

Majira, Amel; Domin, Monique; Grandjean, Olivier; Gofron, Krystyna; Houba-Hérin, Nicole

2002-10-01

A seedling lethal mutant of Nicotiana plumbaginifolia (sdl-1) was isolated by transposon tagging using a maize Dissociation (Ds) element. The insertion mutation was produced by direct co-transformation of protoplasts with two plasmids: one containing Ds and a second with an Ac transposase gene. sdl-1 seedlings exhibit several phenotypes: swollen organs, short hypocotyls in light and dark conditions, and enlarged and multinucleated cells, that altogether suggest cell growth defects. Mutant cells are able to proliferate under in vitro culture conditions. Genomic DNA sequences bordering the transposon were used to recover cDNA from the normal allele. Complementation of the mutant phenotype with the cDNA confirmed that the transposon had caused the mutation. The Ds element was inserted into the first exon of the open reading frame and the homozygous mutant lacked detectable transcript. Phenocopies of the mutant were obtained by an antisense approach. SDL-1 encodes a novel protein found in several plant genomes but apparently missingfrom animal and fungal genomes; the protein is highly conserved and has a potential plastid targeting motif.

Impact of CHA2DS2VASc Score on Candidacy for Anticoagulation in Patients With Atrial Fibrillation: A Multi-payer Analysis.

PubMed

Patel, Aarti A; Nelson, Winnie W; Schein, Jeff

2016-10-01

The purpose of this study is to report on the effect of using CHA 2 DS 2 VASc (congestive heart failure, hypertension, age ≥75 years [doubled], type 1 or type 2 diabetes mellitus, stroke or transient ischemic attack or thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease, or aortic plaque], age 65-75 years, sex category [female]) rather than CHADS 2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke) to determine candidacy for anticoagulant prophylaxis in insured patients with atrial fibrillation (AF). Six administrative claims databases that included medical and pharmacy claims for patients aged ≥18 years with a new or existing diagnosis of AF and patient outcomes assessed for 1 year after diagnosis were analyzed. Retrospective health plan data analyses were performed using a software tool (Anticoagulant Quality Improvement Analyzer). Study measures included stroke risk (identified by CHADS 2 and CHA 2 DS 2 VASc scores), bleeding risk (identified by the Anticoagulation and Risk Factors in Atrial Fibrillation score), and anticoagulant use. A total of 115,906 patients with AF (range of mean ages among the 6 databases, 56-79 years) met the inclusion criteria. All ranges reported represent the minimum and maximum values among the 6 databases. Using the CHA 2 DS 2 VASc compared with the CHADS 2 index to assess stroke risk resulted in a 23% to 32% increase in patients considered potential candidates for anticoagulant prophylaxis. This translated to a 38% to 114% increase in the number of ostensibly undertreated patients. Among patients with high stroke and low bleeding risk, 18% to 28% more patients were considered potential candidates for anticoagulation treatment using CHA 2 DS 2 VASc compared with CHADS 2 , or a 57% to 151% increase in the number of undertreated patients. Use of the CHA 2 DS 2 VASc score to determine the risk of stroke increased the number of AF patients for

Measurement of the Absolute Branching Fraction of Ds+→τ+ντ Decay

NASA Astrophysics Data System (ADS)

Ecklund, K. M.; Love, W.; Savinov, V.; Lopez, A.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sultana, N.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, L. M.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Rademacker, J.; Asner, D. M.; Edwards, K. W.; Naik, P.; Reed, J.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.; Alexander, J. P.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Mehrabyan, S.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Libby, J.; Powell, A.; Wilkinson, G.

2008-04-01

Using a sample of tagged Ds+ decays collected near the Ds*±Ds∓ peak production energy in e+e- collisions with the CLEO-c detector, we study the leptonic decay Ds+→τ+ντ via the decay channel τ+→e+νeν¯τ. We measure B(Ds+→τ+ντ)=(6.17±0.71±0.34)%, where the first error is statistical and the second systematic. Combining this result with our measurements of Ds+→μ+νμ and Ds+→τ+ντ (via τ+→π+ν¯τ), we determine fDs=(274±10±5)MeV.

KiDS-i-800: comparing weak gravitational lensing measurements from same-sky surveys

NASA Astrophysics Data System (ADS)

Amon, A.; Heymans, C.; Klaes, D.; Erben, T.; Blake, C.; Hildebrandt, H.; Hoekstra, H.; Kuijken, K.; Miller, L.; Morrison, C. B.; Choi, A.; de Jong, J. T. A.; Glazebrook, K.; Irisarri, N.; Joachimi, B.; Joudaki, S.; Kannawadi, A.; Lidman, C.; Napolitano, N.; Parkinson, D.; Schneider, P.; van Uitert, E.; Viola, M.; Wolf, C.

2018-07-01

We present a weak gravitational lensing analysis of 815 deg2 of i-band imaging from the Kilo-Degree Survey (KiDS-i-800). In contrast to the deep r-band observations, which take priority during excellent seeing conditions and form the primary KiDS data set (KiDS-r-450), the complementary yet shallower KiDS-i-800 spans a wide range of observing conditions. The overlapping KiDS-i-800 and KiDS-r-450 imaging therefore provides a unique opportunity to assess the robustness of weak lensing measurements. In our analysis we introduce two new `null' tests. The `nulled' two-point shear correlation function uses a matched catalogue to show that the calibrated KiDS-i-800 and KiDS-r-450 shear measurements agree at the level of 1 ± 4 per cent. We use five galaxy lens samples to determine a `nulled' galaxy-galaxy lensing signal from the full KiDS-i-800 and KiDS-r-450 surveys and find that the measurements agree to 7 ± 5 per cent when the KiDS-i-800 source redshift distribution is calibrated using either spectroscopic redshifts, or the 30-band photometric redshifts from the COSMOS survey.

Complex interactions between phytochemicals. The multi-target therapeutic concept of phytotherapy.

PubMed

Efferth, Thomas; Koch, Egon

2011-01-01

Drugs derived from natural resources represent a significant segment of the pharmaceutical market as compared to randomly synthesized compounds. It is a goal of drug development programs to design selective ligands that act on single disease targets to obtain highly effective and safe drugs with low side effects. Although this strategy was successful for many new therapies, there is a marked decline in the number of new drugs introduced into clinical practice over the past decades. One reason for this failure may be due to the fact that the pathogenesis of many diseases is rather multi-factorial in nature and not due to a single cause. Phytotherapy, whose therapeutic efficacy is based on the combined action of a mixture of constituents, offers new treatment opportunities. Because of their biological defence function, plant secondary metabolites act by targeting and disrupting the cell membrane, by binding and inhibiting specific proteins or they adhere to or intercalate into RNA or DNA. Phytotherapeutics may exhibit pharmacological effects by the synergistic or antagonistic interaction of many phytochemicals. Mechanistic reasons for interactions are bioavailability, interference with cellular transport processes, activation of pro-drugs or deactivation of active compounds to inactive metabolites, action of synergistic partners at different points of the same signalling cascade (multi-target effects) or inhibition of binding to target proteins. "-Omics" technologies and systems biology may facilitate unravelling synergistic effects of herbal mixtures.

Measurement of the CP-violating phase ϕs in Bs(0)→Ds(+)Ds(-) decays.

PubMed

Aaij, R; Abellán Beteta, C; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Anderson, J; Andreassen, R; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M-O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; Brett, D; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Brown, H; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cenci, R; Charles, M; Charpentier, Ph; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Counts, I; Couturier, B; Cowan, G A; Craik, D C; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dalseno, J; David, P; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dreimanis, K; Dujany, G; Dupertuis, F; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elena, E; Elsasser, Ch; Ely, S; Esen, S; Evans, H-M; Evans, T; Falabella, A; Färber, C; Farinelli, C; Farley, N; Farry, S; Fay, R F; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fol, P; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garofoli, J; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gavardi, L; Gavrilov, G; Geraci, A; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianelle, A; Gianì, S; Gibson, V; Giubega, L; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gotti, C; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Griffith, P; Grillo, L; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hamilton, B; Hampson, T; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; He, J; Head, T; Heijne, V; Hennessy, K; Henrard, P; Henry, L; Hernando Morata, J A; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hoballah, M; Hombach, C; Hulsbergen, W; Hunt, P; Hussain, N; Hutchcroft, D; Hynds, D; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jalocha, J; Jans, E; Jaton, P; Jawahery, A; Jing, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kaballo, M; Kandybei, S; Kanso, W; Karacson, M; Karbach, T M; Karodia, S; Kelsey, M; Kenyon, I R; Ketel, T; Khanji, B; Khurewathanakul, C; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kurek, K; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Lohn, S; Longstaff, I; Lopes, J H; Lopez-March, N; Lowdon, P; Lucchesi, D; Luo, H; Lupato, A; Luppi, E; Lupton, O; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Mapelli, A; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Märki, R; Marks, J; Martellotti, G; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; McSkelly, B; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M-N; Moggi, N; Molina Rodriguez, J; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A-B; Mountain, R; Muheim, F; Müller, K; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, G; Orlandea, M; Otalora Goicochea, J M; Otto, A; Owen, P; Oyanguren, A; Pal, B K; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pazos Alvarez, A; Pearce, A; Pellegrino, A; Pepe Altarelli, M; Perazzini, S; Perez Trigo, E; Perret, P; Perrin-Terrin, M; Pescatore, L; Pesen, E; Petridis, K; Petrolini, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Pistone, A; Playfer, S; Plo Casasus, M; Polci, F; Poluektov, A; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Price, J D; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rachwal, B; Rademacker, J H; Rakotomiaramanana, B; Rama, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redi, F; Reichert, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rotondo, M; Rouvinet, J; Ruf, T; Ruiz, H; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrie, M; Savrina, D; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Sepp, I; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Silva Coutinho, R; Simi, G; Sirendi, M; Skidmore, N; Skillicorn, I; Skwarnicki, T; Smith, N A; Smith, E; Smith, E; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Stroili, R; Subbiah, V K; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szilard, D; Szumlak, T; T'Jampens, S; Teklishyn, M; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Todd, J; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Websdale, D; Whitehead, M; Wicht, J; Wiedner, D; Wilkinson, G; Williams, M P; Williams, M; Wilschut, H W; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wright, S; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L

2014-11-21

We present a measurement of the CP-violating weak mixing phase ϕs using the decay Bs(0)→Ds(+)Ds(-) in a data sample corresponding to 3.0 fb(-1) of integrated luminosity collected with the LHCb detector in pp collisions at center-of-mass energies of 7 and 8 TeV. An analysis of the time evolution of the system, which does not use the constraint |λ|=1 to allow for the presence of CP violation in decay, yields ϕs=0.02±0.17(stat)±0.02(syst)  rad, |λ|=0.91(-0.15)(+0.18)(stat)±0.02(syst). This result is consistent with the standard model expectation.

DS02R1: Improvements to Atomic Bomb Survivors' Input Data and Implementation of Dosimetry System 2002 (DS02) and Resulting Changes in Estimated Doses.

PubMed

Cullings, H M; Grant, E J; Egbert, S D; Watanabe, T; Oda, T; Nakamura, F; Yamashita, T; Fuchi, H; Funamoto, S; Marumo, K; Sakata, R; Kodama, Y; Ozasa, K; Kodama, K

2017-01-01

Individual dose estimates calculated by Dosimetry System 2002 (DS02) for the Life Span Study (LSS) of atomic bomb survivors are based on input data that specify location and shielding at the time of the bombing (ATB). A multi-year effort to improve information on survivors' locations ATB has recently been completed, along with comprehensive improvements in their terrain shielding input data and several improvements to computational algorithms used in combination with DS02 at RERF. Improvements began with a thorough review and prioritization of original questionnaire data on location and shielding that were taken from survivors or their proxies in the period 1949-1963. Related source documents varied in level of detail, from relatively simple lists to carefully-constructed technical drawings of structural and other shielding and surrounding neighborhoods. Systematic errors were reduced in this work by restoring the original precision of map coordinates that had been truncated due to limitations in early data processing equipment and by correcting distortions in the old (WWII-era) maps originally used to specify survivors' positions, among other improvements. Distortion errors were corrected by aligning the old maps and neighborhood drawings to orthophotographic mosaics of the cities that were newly constructed from pre-bombing aerial photographs. Random errors that were reduced included simple transcription errors and mistakes in identifying survivors' locations on the old maps. Terrain shielding input data that had been originally estimated for limited groups of survivors using older methods and data sources were completely re-estimated for all survivors using new digital terrain elevation data. Improvements to algorithms included a fix to an error in the DS02 code for coupling house and terrain shielding, a correction for elevation at the survivor's location in calculating angles to the horizon used for terrain shielding input, an improved method for truncating

Earth & Space Science PhDs, Class of 2001.

ERIC Educational Resources Information Center

Claudy, Nicholas; Henly, Megan; Migdalski, Chet

This study documents the employment patterns and demographic characteristics of recent PhDs in earth and space science. It summarizes the latest annual survey of recent earth and space science PhDs conducted by the American Geological Institute, the American Geophysical Union, and the Statistical Research Center of the American Institute of…

Dalitz plot analysis of Ds+→K+K-π+

NASA Astrophysics Data System (ADS)

Del Amo Sanchez, P.; Lees, J. P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D. A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Khan, A.; Blinov, V. E.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Kravchenko, E. A.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Yushkov, A. N.; Bondioli, M.; Curry, S.; Kirkby, D.; Lankford, A. J.; Mandelkern, M.; Martin, E. C.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Campagnari, C.; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C.; Eisner, A. M.; Heusch, C. A.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Winstrom, L. O.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Hitlin, D. G.; Ongmongkolkul, P.; Porter, F. C.; Rakitin, A. Y.; Andreassen, R.; Dubrovin, M. S.; Mancinelli, G.; Meadows, B. T.; Sokoloff, M. D.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Jasper, H.; Karbach, T. M.; Petzold, A.; Spaan, B.; Kobel, M. J.; Schubert, K. R.; Schwierz, R.; Bernard, D.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Andreotti, M.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cecchi, A.; Cibinetto, G.; Fioravanti, E.; Franchini, P.; Garzia, I.; Luppi, E.; Munerato, M.; Negrini, M.; Petrella, A.; Piemontese, L.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Nicolaci, M.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Tosi, S.; Bhuyan, B.; Prasad, V.; Lee, C. L.; Morii, M.; Edwards, A. J.; Adametz, A.; Marks, J.; Uwer, U.; Bernlochner, F. U.; Ebert, M.; Lacker, H. M.; Lueck, T.; Volk, A.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Mallik, U.; Chen, C.; Cochran, J.; Crawley, H. B.; Dong, L.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Davier, M.; Derkach, D.; Firmino da Costa, J.; Grosdidier, G.; Le Diberder, F.; Lutz, A. M.; Malaescu, B.; Perez, A.; Roudeau, P.; Schune, M. H.; Serrano, J.; Sordini, V.; Stocchi, A.; Wang, L.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Chavez, C. A.; Coleman, J. P.; Fry, J. R.; Gabathuler, E.; Gamet, R.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Wren, A. C.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; Anderson, J.; Cenci, R.; Jawahery, A.; Roberts, D. A.; Simi, G.; Tuggle, J. M.; Dallapiccola, C.; Salvati, E.; Cowan, R.; Dujmic, D.; Sciolla, G.; Zhao, M.; Lindemann, D.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Nguyen, X.; Simard, M.; Taras, P.; de Nardo, G.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; Losecco, J. M.; Wang, W. F.; Corwin, L. A.; Honscheid, K.; Kass, R.; Morris, J. P.; Blount, N. L.; Brau, J.; Frey, R.; Igonkina, O.; Kolb, J. A.; Rahmat, R.; Sinev, N. B.; Strom, D.; Strube, J.; Torrence, E.; Castelli, G.; Feltresi, E.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Ben-Haim, E.; Bonneaud, G. R.; Briand, H.; Calderini, G.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Prendki, J.; Sitt, S.; Biasini, M.; Manoni, E.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Neri, N.; Paoloni, E.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Baracchini, E.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Li Gioi, L.; Mazzoni, M. A.; Piredda, G.; Renga, F.; Hartmann, T.; Leddig, T.; Schröder, H.; Waldi, R.; Adye, T.; Franek, B.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Hamel de Monchenault, G.; Vasseur, G.; Yèche, Ch.; Zito, M.; Allen, M. T.; Aston, D.; Bard, D. J.; Bartoldus, R.; Benitez, J. F.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Field, R. C.; Franco Sevilla, M.; Fulsom, B. G.; Gabareen, A. M.; Graham, M. T.; Grenier, P.; Hast, C.; Innes, W. R.; Kelsey, M. H.; Kim, H.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Li, S.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; Macfarlane, D. B.; Marsiske, H.; Muller, D. R.; Neal, H.; Nelson, S.; O'Grady, C. P.; Ofte, I.; Perl, M.; Pulliam, T.; Ratcliff, B. N.; Roodman, A.; Salnikov, A. A.; Santoro, V.; Schindler, R. H.; Schwiening, J.; Snyder, A.; Su, D.; Sullivan, M. K.; Sun, S.; Suzuki, K.; Thompson, J. M.; Va'Vra, J.; Wagner, A. P.; Weaver, M.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Yarritu, A. K.; Young, C. C.; Ziegler, V.; Chen, X. R.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Randle-Conde, A.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Miyashita, T. S.; Ahmed, S.; Alam, M. S.; Ernst, J. A.; Pan, B.; Saeed, M. A.; Zain, S. B.; Guttman, N.; Soffer, A.; Lund, P.; Spanier, S. M.; Eckmann, R.; Ritchie, J. L.; Ruland, A. M.; Schilling, C. J.; Schwitters, R. F.; Wray, B. C.; Izen, J. M.; Lou, X. C.; Bianchi, F.; Gamba, D.; Pelliccioni, M.; Bomben, M.; Lanceri, L.; Vitale, L.; Lopez-March, N.; Martinez-Vidal, F.; Oyanguren, A.; Albert, J.; Banerjee, Sw.; Choi, H. H. F.; Hamano, K.; King, G. J.; Kowalewski, R.; Lewczuk, M. J.; Lindsay, C.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Gershon, T. J.; Harrison, P. F.; Latham, T. E.; Pennington, M. R.; Puccio, E. M. T.; Band, H. R.; Dasu, S.; Flood, K. T.; Pan, Y.; Prepost, R.; Vuosalo, C. O.; Wu, S. L.

2011-03-01

We perform a Dalitz plot analysis of about 100 000 Ds+ decays to K+K-π+ and measure the complex amplitudes of the intermediate resonances which contribute to this decay mode. We also measure the relative branching fractions of Ds+→K+K+π- and Ds+→K+K+K-. For this analysis we use a 384 fb-1 data sample, recorded by the BABAR detector at the PEP-II asymmetric-energy e+e- collider running at center-of-mass energies near 10.58 GeV.

Multi-Targeted Antithrombotic Therapy for Total Artificial Heart Device Patients.

PubMed

Ramirez, Angeleah; Riley, Jeffrey B; Joyce, Lyle D

2016-03-01

To prevent thrombotic or bleeding events in patients receiving a total artificial heart (TAH), agents have been used to avoid adverse events. The purpose of this article is to outline the adoption and results of a multi-targeted antithrombotic clinical procedure guideline (CPG) for TAH patients. Based on literature review of TAH anticoagulation and multiple case series, a CPG was designed to prescribe the use of multiple pharmacological agents. Total blood loss, Thromboelastograph(®) (TEG), and platelet light-transmission aggregometry (LTA) measurements were conducted on 13 TAH patients during the first 2 weeks of support in our institution. Target values and actual medians for postimplant days 1, 3, 7, and 14 were calculated for kaolinheparinase TEG, kaolin TEG, LTA, and estimated blood loss. Protocol guidelines were followed and anticoagulation management reduced bleeding and prevented thrombus formation as well as thromboembolic events in TAH patients postimplantation. The patients in this study were susceptible to a variety of possible complications such as mechanical device issues, thrombotic events, infection, and bleeding. Among them all it was clear that patients were at most risk for bleeding, particularly on postoperative days 1 through 3. However, bleeding was reduced into postoperative days 3 and 7, indicating that acceptable hemostasis was achieved with the anticoagulation protocol. The multidisciplinary, multi-targeted anticoagulation clinical procedure guideline was successful to maintain adequate antithrombotic therapy for TAH patients.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

A multi-criteria targeting approach to neutral grassland conservation.

PubMed

Bayliss, Julian; Helyar, Alice; Lee, John T; Thompson, Stewart

2003-02-01

Resources for creating and managing rare habitats are limited, and a targeting approach aimed at identifying the most viable sites for habitat conservation is therefore desirable. This study developed a multi-criteria targeting approach to site conservation for two rare grassland types, based on a suite of biotic and abiotic factors managed within a Geographical Information System. A number of biotic and abiotic criteria were assessed to evaluate the biodiversity status of grassland sites. Biotic factors included species diversity, species richness and species rarity; and abiotic factors included patch area, position in the ecological unit and the influence of surrounding land use. Each criterion was given equal weighting and a final biodiversity value for each patch was calculated; the patch with the highest cumulative rank score was deemed the patch with the greatest biodiversity. Each site was then examined in relation to agricultural land under the existing management prescriptions of the Upper Thames Tributaries Environmentally Sensitive Area (UTTESA). Sites identified with high biodiversity potential, but currently not included under management prescriptions, were targeted for future inclusion in the ESA scheme. The targeting approach demonstrated how the national Lowland Meadows habitat action plan creation target of 500 ha could be achieved in the UTTESA. The fact that this target figure was so easily attained within this study area highlighted the possible underestimation of national habitat creation targets.

Antitumor Activity and Induction of TP53-Dependent Apoptosis toward Ovarian Clear Cell Adenocarcinoma by the Dual PI3K/mTOR Inhibitor DS-7423

PubMed Central

Kashiyama, Tomoko; Oda, Katsutoshi; Ikeda, Yuji; Shiose, Yoshinobu; Hirota, Yasuhide; Inaba, Kanako; Makii, Chinami; Kurikawa, Reiko; Miyasaka, Aki; Koso, Takahiro; Fukuda, Tomohiko; Tanikawa, Michihiro; Shoji, Keiko; Sone, Kenbun; Arimoto, Takahide; Wada-Hiraike, Osamu; Kawana, Kei; Nakagawa, Shunsuke; Matsuda, Koichi; McCormick, Frank; Aburatani, Hiroyuki; Yano, Tetsu; Osuga, Yutaka; Fujii, Tomoyuki

2014-01-01

DS-7423, a novel, small-molecule dual inhibitor of phosphatidylinositol-3-kinase (PI3K) and mammalian target of rapamycin (mTOR), is currently in phase I clinical trials for solid tumors. Although DS-7423 potently inhibits PI3Kα (IC50 = 15.6 nM) and mTOR (IC50 = 34.9 nM), it also inhibits other isoforms of class I PI3K (IC50 values: PI3Kβ = 1,143 nM; PI3Kγ = 249 nM; PI3Kδ = 262 nM). The PI3K/mTOR pathway is frequently activated in ovarian clear cell adenocarcinomas (OCCA) through various mutations that activate PI3K-AKT signaling. Here, we describe the anti-tumor effect of DS-7423 on a panel of nine OCCA cell lines. IC50 values for DS-7423 were <75 nM in all the lines, regardless of the mutational status of PIK3CA. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. Flow cytometry analysis revealed a decrease in S-phase cell populations in all the cell lines and an increase in sub-G1 cell populations following treatment with DS-7423 in six of the nine OCCA cell lines tested. DS-7423-mediated apoptosis was induced more effectively in the six cell lines without TP53 mutations than in the three cell lines with TP53 mutations. Concomitantly with the decreased phosphorylation level of MDM2 (mouse double minute 2 homolog), the level of phosphorylation of TP53 at Ser46 was increased by DS-7423 in the six cell lines with wild-type TP53, with induction of genes that mediate TP53-dependent apoptosis, including p53AIP1 and PUMA at 39 nM or higher doses. Our data suggest that the dual PI3K/mTOR inhibitor DS-7423 may constitute a promising molecular targeted therapy for OCCA, and that its antitumor effect might be partly obtained by induction of TP53-dependent apoptosis in TP53 wild-type OCCAs. PMID:24504419

Measurement of the mass and width of the Ds1(2536)+ meson

NASA Astrophysics Data System (ADS)

Lees, J. P.; Poireau, V.; Prencipe, E.; Tisserand, V.; Garra Tico, J.; Grauges, E.; Martinelli, M.; Milanes, D. A.; Palano, A.; Pappagallo, M.; Eigen, G.; Stugu, B.; Sun, L.; Brown, D. N.; Kerth, L. T.; Kolomensky, Yu. G.; Lynch, G.; Osipenkov, I. L.; Koch, H.; Schroeder, T.; Asgeirsson, D. J.; Hearty, C.; Mattison, T. S.; McKenna, J. A.; Khan, A.; Blinov, V. E.; Buzykaev, A. R.; Druzhinin, V. P.; Golubev, V. B.; Kravchenko, E. A.; Onuchin, A. P.; Serednyakov, S. I.; Skovpen, Yu. I.; Solodov, E. P.; Todyshev, K. Yu.; Yushkov, A. N.; Bondioli, M.; Curry, S.; Kirkby, D.; Lankford, A. J.; Mandelkern, M.; Stoker, D. P.; Atmacan, H.; Gary, J. W.; Liu, F.; Long, O.; Vitug, G. M.; Campagnari, C.; Hong, T. M.; Kovalskyi, D.; Richman, J. D.; West, C. A.; Eisner, A. M.; Kroseberg, J.; Lockman, W. S.; Martinez, A. J.; Schalk, T.; Schumm, B. A.; Seiden, A.; Cheng, C. H.; Doll, D. A.; Echenard, B.; Flood, K. T.; Hitlin, D. G.; Ongmongkolkul, P.; Porter, F. C.; Rakitin, A. Y.; Andreassen, R.; Dubrovin, M. S.; Meadows, B. T.; Sokoloff, M. D.; Bloom, P. C.; Ford, W. T.; Gaz, A.; Nagel, M.; Nauenberg, U.; Smith, J. G.; Wagner, S. R.; Ayad, R.; Toki, W. H.; Jasper, H.; Petzold, A.; Spaan, B.; Kobel, M. J.; Schubert, K. R.; Schwierz, R.; Bernard, D.; Verderi, M.; Clark, P. J.; Playfer, S.; Watson, J. E.; Bettoni, D.; Bozzi, C.; Calabrese, R.; Cibinetto, G.; Fioravanti, E.; Garzia, I.; Luppi, E.; Munerato, M.; Negrini, M.; Piemontese, L.; Baldini-Ferroli, R.; Calcaterra, A.; de Sangro, R.; Finocchiaro, G.; Nicolaci, M.; Pacetti, S.; Patteri, P.; Peruzzi, I. M.; Piccolo, M.; Rama, M.; Zallo, A.; Contri, R.; Guido, E.; Lo Vetere, M.; Monge, M. R.; Passaggio, S.; Patrignani, C.; Robutti, E.; Bhuyan, B.; Prasad, V.; Lee, C. L.; Morii, M.; Edwards, A. J.; Adametz, A.; Marks, J.; Uwer, U.; Bernlochner, F. U.; Ebert, M.; Lacker, H. M.; Lueck, T.; Dauncey, P. D.; Tibbetts, M.; Behera, P. K.; Mallik, U.; Chen, C.; Cochran, J.; Crawley, H. B.; Meyer, W. T.; Prell, S.; Rosenberg, E. I.; Rubin, A. E.; Gritsan, A. V.; Guo, Z. J.; Arnaud, N.; Davier, M.; Derkach, D.; Firmino da Costa, J.; Grosdidier, G.; Le Diberder, F.; Lutz, A. M.; Malaescu, B.; Perez, A.; Roudeau, P.; Schune, M. H.; Stocchi, A.; Wang, L.; Wormser, G.; Lange, D. J.; Wright, D. M.; Bingham, I.; Chavez, C. A.; Coleman, J. P.; Fry, J. R.; Gabathuler, E.; Hutchcroft, D. E.; Payne, D. J.; Touramanis, C.; Bevan, A. J.; di Lodovico, F.; Sacco, R.; Sigamani, M.; Cowan, G.; Paramesvaran, S.; Wren, A. C.; Brown, D. N.; Davis, C. L.; Denig, A. G.; Fritsch, M.; Gradl, W.; Hafner, A.; Alwyn, K. E.; Bailey, D.; Barlow, R. J.; Jackson, G.; Lafferty, G. D.; Cenci, R.; Hamilton, B.; Jawahery, A.; Roberts, D. A.; Simi, G.; Dallapiccola, C.; Salvati, E.; Cowan, R.; Dujmic, D.; Sciolla, G.; Lindemann, D.; Patel, P. M.; Robertson, S. H.; Schram, M.; Biassoni, P.; Lazzaro, A.; Lombardo, V.; Palombo, F.; Stracka, S.; Cremaldi, L.; Godang, R.; Kroeger, R.; Sonnek, P.; Summers, D. J.; Nguyen, X.; Taras, P.; de Nardo, G.; Monorchio, D.; Onorato, G.; Sciacca, C.; Raven, G.; Snoek, H. L.; Jessop, C. P.; Knoepfel, K. J.; Losecco, J. M.; Wang, W. F.; Corwin, L. A.; Honscheid, K.; Kass, R.; Blount, N. L.; Brau, J.; Frey, R.; Kolb, J. A.; Rahmat, R.; Sinev, N. B.; Strom, D.; Strube, J.; Torrence, E.; Castelli, G.; Feltresi, E.; Gagliardi, N.; Margoni, M.; Morandin, M.; Posocco, M.; Rotondo, M.; Simonetto, F.; Stroili, R.; Ben-Haim, E.; Bomben, M.; Bonneaud, G. R.; Briand, H.; Calderini, G.; Chauveau, J.; Hamon, O.; Leruste, Ph.; Marchiori, G.; Ocariz, J.; Sitt, S.; Biasini, M.; Manoni, E.; Rossi, A.; Angelini, C.; Batignani, G.; Bettarini, S.; Carpinelli, M.; Casarosa, G.; Cervelli, A.; Forti, F.; Giorgi, M. A.; Lusiani, A.; Neri, N.; Paoloni, E.; Rizzo, G.; Walsh, J. J.; Lopes Pegna, D.; Lu, C.; Olsen, J.; Smith, A. J. S.; Telnov, A. V.; Anulli, F.; Cavoto, G.; Faccini, R.; Ferrarotto, F.; Ferroni, F.; Gaspero, M.; Li Gioi, L.; Mazzoni, M. A.; Piredda, G.; Buenger, C.; Hartmann, T.; Leddig, T.; Schröder, H.; Waldi, R.; Adye, T.; Olaiya, E. O.; Wilson, F. F.; Emery, S.; Hamel de Monchenault, G.; Vasseur, G.; Yèche, Ch.; Allen, M. T.; Aston, D.; Bard, D. J.; Bartoldus, R.; Benitez, J. F.; Cartaro, C.; Convery, M. R.; Dorfan, J.; Dubois-Felsmann, G. P.; Dunwoodie, W.; Field, R. C.; Franco Sevilla, M.; Fulsom, B. G.; Gabareen, A. M.; Graham, M. T.; Grenier, P.; Hast, C.; Innes, W. R.; Kelsey, M. H.; Kim, H.; Kim, P.; Kocian, M. L.; Leith, D. W. G. S.; Lewis, P.; Li, S.; Lindquist, B.; Luitz, S.; Luth, V.; Lynch, H. L.; Macfarlane, D. B.; Muller, D. R.; Neal, H.; Nelson, S.; O'Grady, C. P.; Ofte, I.; Perl, M.; Pulliam, T.; Ratcliff, B. N.; Robertson, S. H.; Roodman, A.; Salnikov, A. A.; Santoro, V.; Schindler, R. H.; Schwiening, J.; Snyder, A.; Su, D.; Sullivan, M. K.; Sun, S.; Suzuki, K.; Thompson, J. M.; Va'Vra, J.; Wagner, A. P.; Weaver, M.; Wisniewski, W. J.; Wittgen, M.; Wright, D. H.; Wulsin, H. W.; Yarritu, A. K.; Young, C. C.; Ziegler, V.; Chen, X. R.; Park, W.; Purohit, M. V.; White, R. M.; Wilson, J. R.; Randle-Conde, A.; Sekula, S. J.; Bellis, M.; Burchat, P. R.; Miyashita, T. S.; Alam, M. S.; Ernst, J. A.; Guttman, N.; Soffer, A.; Lund, P.; Spanier, S. M.; Eckmann, R.; Ritchie, J. L.; Ruland, A. M.; Schilling, C. J.; Schwitters, R. F.; Wray, B. C.; Izen, J. M.; Lou, X. C.; Bianchi, F.; Gamba, D.; Pelliccioni, M.; Lanceri, L.; Vitale, L.; Lopez-March, N.; Martinez-Vidal, F.; Oyanguren, A.; Ahmed, H.; Albert, J.; Banerjee, Sw.; Choi, H. H. F.; Hamano, K.; King, G. J.; Kowalewski, R.; Lewczuk, M. J.; Lindsay, C.; Nugent, I. M.; Roney, J. M.; Sobie, R. J.; Gershon, T. J.; Harrison, P. F.; Latham, T. E.; Puccio, E. M. T.; Band, H. R.; Dasu, S.; Pan, Y.; Prepost, R.; Vuosalo, C. O.; Wu, S. L.

2011-04-01

The decay width and mass of the Ds1(2536)+ meson are measured via the decay channel Ds1+→D*+KS0 using 385fb-1 of data recorded with the BABAR detector in the vicinity of the Υ(4S) resonance at the PEP-II asymmetric-energy electron-positron collider. The result for the decay width is Γ(Ds1+)=0.92±0.03(stat.)±0.04(syst.)MeV. For the mass, a value of m(Ds1+)=2535.08±0.01(stat.)±0.15(syst.)MeV/c2 is obtained. The mass difference between the Ds1+ and the D*+ is measured to be m(Ds1+)-m(D*+)=524.83±0.01(stat.)±0.04(syst.)MeV/c2, representing a significant improvement compared to the current world average. The unnatural spin-parity assignment for the Ds1+ meson is confirmed.

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

PubMed

Byrne, Susan M; Ortiz, Luis; Mali, Prashant; Aach, John; Church, George M

2015-02-18

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Transgenic soybean plants expressing Spb18S dsRNA exhibit enhanced resistance to the soybean pod borer Leguminivora glycinivorella (Lepidoptera: Olethreutidae).

PubMed

Wang, Zhanchun; Li, Tianyu; Ni, Hejia; Wang, Guoyue; Liu, Xinxin; Cao, Yingxue; Li, Wenbin; Meng, Fanli

2018-06-01

The soybean pod borer [SPB; Leguminivora glycinivorella (Mats.) Obraztsov] is a major soybean pest in northeastern Asia. A useful method for addressing this problem is the generation of transgenic plants producing double-stranded RNA (dsRNA) that target essential insect genes. In this study, we confirmed that 18S ribosomal RNA is critical for SPB development. Downregulated Spb18S expression induced by dsRNA injection increased larval mortality rates and resulted in early pupation. We also assessed whether Spb18S is silenced in SPB larvae fed on transgenic soybean expressing Spb18S dsRNA. Transgenic plants downregulated Spb18S expression levels and second-instar larval survival rates. Moreover, such plants were less damaged by SPB larvae than control plants under field conditions. © 2018 Wiley Periodicals, Inc.

TargetCrys: protein crystallization prediction by fusing multi-view features with two-layered SVM.

PubMed

Hu, Jun; Han, Ke; Li, Yang; Yang, Jing-Yu; Shen, Hong-Bin; Yu, Dong-Jun

2016-11-01

The accurate prediction of whether a protein will crystallize plays a crucial role in improving the success rate of protein crystallization projects. A common critical problem in the development of machine-learning-based protein crystallization predictors is how to effectively utilize protein features extracted from different views. In this study, we aimed to improve the efficiency of fusing multi-view protein features by proposing a new two-layered SVM (2L-SVM) which switches the feature-level fusion problem to a decision-level fusion problem: the SVMs in the 1st layer of the 2L-SVM are trained on each of the multi-view feature sets; then, the outputs of the 1st layer SVMs, which are the "intermediate" decisions made based on the respective feature sets, are further ensembled by a 2nd layer SVM. Based on the proposed 2L-SVM, we implemented a sequence-based protein crystallization predictor called TargetCrys. Experimental results on several benchmark datasets demonstrated the efficacy of the proposed 2L-SVM for fusing multi-view features. We also compared TargetCrys with existing sequence-based protein crystallization predictors and demonstrated that the proposed TargetCrys outperformed most of the existing predictors and is competitive with the state-of-the-art predictors. The TargetCrys webserver and datasets used in this study are freely available for academic use at: http://csbio.njust.edu.cn/bioinf/TargetCrys .

Asynchronous, Decentralized DS-CDMA Using Feedback-Controlled Spreading Sequences for Time-Dispersive Channels

NASA Astrophysics Data System (ADS)

Miyatake, Teruhiko; Chiba, Kazuki; Hamamura, Masanori; Tachikawa, Shin'ichi

We propose a novel asynchronous direct-sequence codedivision multiple access (DS-CDMA) using feedback-controlled spreading sequences (FCSSs) (FCSS/DS-CDMA). At the receiver of FCSS/DS-CDMA, the code-orthogonalizing filter (COF) produces a spreading sequence, and the receiver returns the spreading sequence to the transmitter. Then the transmitter uses the spreading sequence as its updated version. The performance of FCSS/DS-CDMA is evaluated over time-dispersive channels. The results indicate that FCSS/DS-CDMA greatly suppresses both the intersymbol interference (ISI) and multiple access interference (MAI) over time-invariant channels. FCSS/DS-CDMA is applicable to the decentralized multiple access.

Galactose-functionalized multi-responsive nanogels for hepatoma-targeted drug delivery

NASA Astrophysics Data System (ADS)

Lou, Shaofeng; Gao, Shan; Wang, Weiwei; Zhang, Mingming; Zhang, Ju; Wang, Chun; Li, Chen; Kong, Deling; Zhao, Qiang

2015-02-01

We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-d-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using a combination of enzymatic transesterification and emulsion copolymerization for intracellular drug delivery. The nanogel exhibited redox, pH and temperature-responsive properties, which can be adjusted by varying the monomer feeding ratio. Furthermore, the volume phase transition temperature (VPTT) of the nanogels was close to body temperature and can result in rapid thermal gelation at 37 °C. Scanning electron microscopy also revealed that the P(ODGal-VCL-MAA) nanogel showed uniform spherical monodispersion. With pyrene as a probe, the fluorescence excitation spectra demonstrated nanogel degradation in response to glutathione (GSH). X-ray diffraction (XRD) showed an amorphous property of DOX within the nanogel, which was used in this study as a model anti-cancer drug. Drug-releasing characteristics of the nanogel were examined in vitro. The results showed multi-responsiveness of DOX release by the variation of environmental pH values, temperature or the availability of GSH, a biological reductase. An in vitro cytotoxicity assay showed a higher anti-tumor activity of the galactose-functionalized DOX-loaded nanogels against human hepatoma HepG2 cells, which was, at least in part, due to specific binding between the galactose segments and the asialoglycoprotein receptors (ASGP-Rs) in hepatic cells. Confocal laser scanning microscopy (CLSM) and flow cytometric profiles further confirmed elevated cellular uptake of DOX by the galactose-functionalised nanogels. Thus, we report here a multi-responsive P(ODGal-VCL-MAA) nanogel with a hepatoma-specific targeting ability for anti-cancer drug delivery.We report here a hepatoma-targeting multi-responsive biodegradable crosslinked nanogel, poly(6-O-vinyladipoyl-d-galactose-ss-N-vinylcaprolactam-ss-methacrylic acid) P(ODGal-VCL-MAA), using

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models.

PubMed

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com .

TargetNet: a web service for predicting potential drug-target interaction profiling via multi-target SAR models

NASA Astrophysics Data System (ADS)

Yao, Zhi-Jiang; Dong, Jie; Che, Yu-Jing; Zhu, Min-Feng; Wen, Ming; Wang, Ning-Ning; Wang, Shan; Lu, Ai-Ping; Cao, Dong-Sheng

2016-05-01

Drug-target interactions (DTIs) are central to current drug discovery processes and public health fields. Analyzing the DTI profiling of the drugs helps to infer drug indications, adverse drug reactions, drug-drug interactions, and drug mode of actions. Therefore, it is of high importance to reliably and fast predict DTI profiling of the drugs on a genome-scale level. Here, we develop the TargetNet server, which can make real-time DTI predictions based only on molecular structures, following the spirit of multi-target SAR methodology. Naïve Bayes models together with various molecular fingerprints were employed to construct prediction models. Ensemble learning from these fingerprints was also provided to improve the prediction ability. When the user submits a molecule, the server will predict the activity of the user's molecule across 623 human proteins by the established high quality SAR model, thus generating a DTI profiling that can be used as a feature vector of chemicals for wide applications. The 623 SAR models related to 623 human proteins were strictly evaluated and validated by several model validation strategies, resulting in the AUC scores of 75-100 %. We applied the generated DTI profiling to successfully predict potential targets, toxicity classification, drug-drug interactions, and drug mode of action, which sufficiently demonstrated the wide application value of the potential DTI profiling. The TargetNet webserver is designed based on the Django framework in Python, and is freely accessible at http://targetnet.scbdd.com.

Clinical evaluation of cobas core anti-dsDNA EIA quant.

PubMed

González, Concepción; Guevara, Paloma; García-Berrocal, Belén; Alejandro Navajo, José; Manuel González-Buitrago, José

2004-01-01

The measurement of antibodies to double-stranded DNA (anti-dsDNA) is a useful tool for the diagnosis and monitoring of patients with connective tissue diseases, particularly systemic lupus erythematosus (SLE). The aim of the present study was to compare a new enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-dsDNA antibodies, which uses purified double-stranded plasmid DNA as the antigen (anti-dsDNA EIA Quant; Roche Diagnostics, Mannheim, Germany), with an established ELISA. The clinical usefulness of this new ELISA was also assessed. We measured anti-dsDNA antibodies in 398 serum samples that were divided into four groups: 1). routine samples sent to our laboratory for an antinuclear antibody (ANA) test (n=229), 2). samples from blood donors (n=74), 3). samples from patients with SLE (n=48), and 4) samples from patients with other autoimmune diseases (n=47). The methods used were the Cobas Core Anti-dsDNA EIA Quant (Roche Diagnostics, Mannheim, Germany) and the Anti-dsDNA test (Gull Diagnostics, Bois d'Arcy, France). We obtained a kappa index and Spearman correlation coefficient in the comparative study, and sensitivity, specificity, predictive values, and likelihood ratios in the clinical study. The results obtained show a good agreement between the two methods in both the qualitative results (kappa=0.91) and the quantitative data (r=0.854). The best accuracy, predictive values, likelihood ratios, and correlation with active disease were obtained with the Roche anti-dsDNA assay. Copyright 2004 Wiley-Liss, Inc.

In-medium properties of pseudoscalar D_s and B_s mesons

NASA Astrophysics Data System (ADS)

Chhabra, Rahul; Kumar, Arvind

2017-11-01

We calculate the shift in the masses and decay constants of D_s(1968) and B_s(5370) mesons in hot and dense asymmetric strange hadronic matter using QCD sum rules and chiral SU(3) model. In-medium strange quark condensates < \\bar{s}s> _{ρ _B}, and gluon condensates < α s/π {G^a}_{μ ν } {G^a}^{μ ν } > _{ρ _B}, to be used in the QCD sum rules for pseudoscalar D_s and B_s mesons, are calculated using a chiral SU(3) model. As an application of our present work, we calculate the in-medium decay widths of the excited (c\\bar{s}) states D_s^*(2715) and D_s^*(2860) decaying to (D_s(1968),η ) mesons. The medium effects in their decay widths are incorporated through the mass modification of the D_s(1968) and η mesons. The results of the present investigation may be helpful in understanding the possible outcomes of the future experiments like CBM and PANDA under the FAIR facility.

Immunomodulatory Effects of dsRNA and Its Potential as Vaccine Adjuvant

PubMed Central

Jin, Bo; Sun, Tao; Yu, Xiao-Hong; Liu, Chao-Qun; Yang, Ying-Xiang; Lu, Ping; Fu, Shan-Feng; Qiu, Hui-Bin; Yeo, Anthony E. T.

2010-01-01

dsRNA can be detected by pattern recognition receptors, for example, TLR3, MDA-5, NLRP3 to induce proinflammatory cytokines responsible for innate/adaptive immunity. Recognized by endosomal TLR3 in myeloid DCs (mDCs), dsRNA can activate mDCs into mature antigen presenting cells (mAPCs) which in turn present antigen epitopes with MHC-I molecules to naïve T cells. Coadministration of protein and synthetic dsRNA analogues can elicit an antigen-specific Th1-polarized immune response which stimulates the CD8+ CTL response and possibly dampen Th17 response. Synthetic dsRNA analogues have been tested as vaccine adjuvant against viral infections in animal models. However, a dsRNA receptor, TLR3 can be expressed in tumor cells while other members of TLR family, for example, TLR4 and TLR2 have been shown to promote tumor progression, metastasis, and chemoresistance. Thus, the promising potential of dsRNA analogues as a tumor therapeutic vaccine adjuvant should be evaluated cautiously. PMID:20671921

Human Immunity and the Design of Multi-Component, Single Target Vaccines

PubMed Central

Saul, Allan; Fay, Michael P.

2007-01-01

Background Inclusion of multiple immunogens to target a single organism is a strategy being pursued for many experimental vaccines, especially where it is difficult to generate a strongly protective response from a single immunogen. Although there are many human vaccines that contain multiple defined immunogens, in almost every case each component targets a different pathogen. As a consequence, there is little practical experience for deciding where the increased complexity of vaccines with multiple defined immunogens vaccines targeting single pathogens will be justifiable. Methodology/Principal Findings A mathematical model, with immunogenicity parameters derived from a database of human responses to established vaccines, was used to predict the increase in the efficacy and the proportion of the population protected resulting from addition of further immunogens. The gains depended on the relative protection and the range of responses in the population to each immunogen and also to the correlation of the responses between immunogens. In most scenarios modeled, the gain in overall efficacy obtained by adding more immunogens was comparable to gains obtained from a single immunogen through the use of better formulations or adjuvants. Multi-component single target vaccines were more effective at decreasing the proportion of poor responders than increasing the overall efficacy of the vaccine in a population. Conclusions/Significance Inclusion of limited number of antigens in a vaccine aimed at targeting a single organism will increase efficacy, but the gains are relatively modest and for a practical vaccine there are constraints that are likely to limit multi-component single target vaccines to a small number of key antigens. The model predicts that this type of vaccine will be most useful where the critical issue is the reduction in proportion of poor responders. PMID:17786221

Higher spin realization of the DS/CFT correspondence

NASA Astrophysics Data System (ADS)

Anninos, Dionysios; Hartman, Thomas; Strominger, Andrew

2017-01-01

We conjecture that Vasiliev’s theory of higher spin gravity in four-dimensional de Sitter space (dS4) is holographically dual to a three-dimensional conformal field theory (CFT3) living on the spacelike boundary of dS4 at future timelike infinity. The CFT3 is the Euclidean Sp(N) vector model with anticommuting scalars. The free CFT3 flows under a double-trace deformation to an interacting CFT3 in the IR. We argue that both CFTs are dual to Vasiliev dS4 gravity but with different future boundary conditions on the bulk scalar field. Our analysis rests heavily on analytic continuations of bulk and boundary correlators in the proposed duality relating the O(N) model with Vasiliev gravity in AdS4.

Laser acceleration of protons using multi-ion plasma gaseous targets

DOE PAGES

Liu, Tung -Chang; Shao, Xi; Liu, Chuan -Sheng; ...

2015-02-01

We present a theoretical and numerical study of a novel acceleration scheme by applying a combination of laser radiation pressure and shielded Coulomb repulsion in laser acceleration of protons in multi-species gaseous targets. By using a circularly polarized CO₂ laser pulse with a wavelength of 10 μm—much greater than that of a Ti: Sapphire laser—the critical density is significantly reduced, and a high-pressure gaseous target can be used to achieve an overdense plasma. This gives us a larger degree of freedom in selecting the target compounds or mixtures, as well as their density and thickness profiles. By impinging such amore » laser beam on a carbon–hydrogen target, the gaseous target is first compressed and accelerated by radiation pressure until the electron layer disrupts, after which the protons are further accelerated by the electron-shielded carbon ion layer. An 80 MeV quasi-monoenergetic proton beam can be generated using a half-sine shaped laser beam with a peak power of 70 TW and a pulse duration of 150 wave periods.« less

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort.

PubMed

Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Massaro, Laura; Marocchi, Elisa; Miranda, Francesca; Spinelli, Francesca Romana; Truglia, Simona; Alessandri, Cristiano; Valesini, Guido

2015-01-01

The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70-98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA - (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA -: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA - (21.1% and 18.7%, resp.; P = 0.001). Serositis resulted significantly more frequent in anti-dsDNA - (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; P < 0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA - (21.8%, P = 0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P = 0.7). Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Statistical inconsistencies in the KiDS-450 data set

NASA Astrophysics Data System (ADS)

Efstathiou, George; Lemos, Pablo

2018-05-01

The Kilo-Degree Survey (KiDS) has been used in several recent papers to infer constraints on the amplitude of the matter power spectrum and matter density at low redshift. Some of these analyses have claimed tension with the Planck Λ cold dark matter cosmology at the ˜2σ-3σ level, perhaps indicative of new physics. However, Planck is consistent with other low-redshift probes of the matter power spectrum such as redshift-space distortions and the combined galaxy-mass and galaxy-galaxy power spectra. Here, we perform consistency tests of the KiDS data, finding internal tensions for various cuts of the data at ˜2.2σ-3.5σ significance. Until these internal tensions are understood, we argue that it is premature to claim evidence for new physics from KiDS. We review the consistency between KiDS and other weak lensing measurements of S8, highlighting the importance of intrinsic alignments for precision cosmology.

Multi-Targeted Agents in Cancer Cell Chemosensitization: What We Learnt from Curcumin Thus Far.

PubMed

Bordoloi, Devivasha; Roy, Nand K; Monisha, Javadi; Padmavathi, Ganesan; Kunnumakkara, Ajaikumar B

2016-01-01

Research over the past several years has developed many mono-targeted therapies for the prevention and treatment of cancer, but it still remains one of the fatal diseases in the world killing 8.2 million people annually. It has been well-established that development of chemoresistance in cancer cells against mono-targeted chemotherapeutic agents by modulation of multiple survival pathways is the major cause of failure of cancer chemotherapy. Therefore, inhibition of these pathways by non-toxic multi-targeted agents may have profoundly high potential in preventing drug resistance and sensitizing cancer cells to chemotherapeutic agents. To study the potential of curcumin, a multi-targeted natural compound, obtained from the plant Turmeric (Curcuma longa) in combination with standard chemotherapeutic agents to inhibit drug resistance and sensitize cancer cells to these agents based on available literature and patents. An extensive literature survey was performed in PubMed and Google for the chemosensitizing potential of curcumin in different cancers published so far and the patents published during 2014-2015. Our search resulted in many in vitro, in vivo and clinical reports signifying the chemosensitizing potential of curcumin in diverse cancers. There were 160 in vitro studies, 62 in vivo studies and 5 clinical studies. Moreover, 11 studies reported on hybrid curcumin: the next generation of curcumin based therapeutics. Also, 34 patents on curcumin's biological activity have been retrieved. Altogether, the present study reveals the enormous potential of curcumin, a natural, non-toxic, multi-targeted agent in overcoming drug resistance in cancer cells and sensitizing them to chemotherapeutic drugs.

In C. elegans, high levels of dsRNA allow RNAi in the absence of RDE-4.

PubMed

Habig, Jeffrey W; Aruscavage, P Joseph; Bass, Brenda L

2008-01-01

C. elegans Dicer requires an accessory double-stranded RNA binding protein, RDE-4, to enact the first step of RNA interference, the cleavage of dsRNA to produce siRNA. While RDE-4 is typically essential for RNAi, we report that in the presence of high concentrations of trigger dsRNA, rde-4 deficient animals are capable of silencing a transgene. By multiple criteria the silencing occurs by the canonical RNAi pathway. For example, silencing is RDE-1 dependent and exhibits a decrease in the targeted mRNA in response to an increase in siRNA. We also find that high concentrations of dsRNA trigger lead to increased accumulation of primary siRNAs, consistent with the existence of a rate-limiting step during the conversion of primary to secondary siRNAs. Our studies also revealed that transgene silencing occurs at low levels in the soma, even in the presence of ADARs, and that at least some siRNAs accumulate in a temperature-dependent manner. We conclude that an RNAi response varies with different conditions, and this may allow an organism to tailor a response to specific environmental signals.

In C. elegans, High Levels of dsRNA Allow RNAi in the Absence of RDE-4

PubMed Central

Habig, Jeffrey W.; Aruscavage, P. Joseph; Bass, Brenda L.

2008-01-01

C. elegans Dicer requires an accessory double-stranded RNA binding protein, RDE-4, to enact the first step of RNA interference, the cleavage of dsRNA to produce siRNA. While RDE-4 is typically essential for RNAi, we report that in the presence of high concentrations of trigger dsRNA, rde-4 deficient animals are capable of silencing a transgene. By multiple criteria the silencing occurs by the canonical RNAi pathway. For example, silencing is RDE-1 dependent and exhibits a decrease in the targeted mRNA in response to an increase in siRNA. We also find that high concentrations of dsRNA trigger lead to increased accumulation of primary siRNAs, consistent with the existence of a rate-limiting step during the conversion of primary to secondary siRNAs. Our studies also revealed that transgene silencing occurs at low levels in the soma, even in the presence of ADARs, and that at least some siRNAs accumulate in a temperature-dependent manner. We conclude that an RNAi response varies with different conditions, and this may allow an organism to tailor a response to specific environmental signals. PMID:19112503

[Pharmaceutical application of cyclodextrins as multi-functional drug carriers].

PubMed

Uekama, Kaneto

2004-12-01

Owing to the increasingly globalized nature of the cyclodextrin (CyD)-related science and technology, development of the CyD-based pharmaceutical formulation is rapidly progressing. The pharmaceutically useful CyDs are classified into hydrophilic, hydrophobic, and ionic derivatives. Because of the multi-functional characteristics and bioadaptability, these CyDs are capable of alleviating the undesirable properties of drug molecules through the formation of inclusion complexes or the form of CyD/drug conjugates. This review outlines the current application of CyDs in drug delivery and pharmaceutical formulation, focusing on the following evidences. 1) The hydrophilic CyDs enhance the rate and extent of bioavailability of poorly water-soluble drugs. 2) The amorphous CyDs such as 2-hydroxypropyl-beta-CyD are useful for inhibition of polymorphic transition and crystallization rates of drugs during storage. 3) The delayed release formulation can be obtained by the use of enteric type CyDs such as O-carboxymethyl-O-ethyl-beta-CyD. 4) The hydrophobic CyDs are useful for modification of the release site and/or time profile of water-soluble drugs with prolonged therapeutic effects. 5) The branched CyDs are particularly effective in inhibiting the adsorption to hydrophobic surface of containers and aggregation of polypeptide and protein drugs. 6) The combined use of different CyDs and/or pharmaceutical additives can serve as more functional drug carriers, improving efficacy and reducing side effects. 7) The CyD/drug conjugates may provide a versatile means for the constructions of not only colonic delivery system but also site-specific drug release system, including gene delivery. On the basis of the above-mentioned knowledge, the advantages and limitations of CyDs in the design of advanced dosage forms will be discussed.

Multi-Target Camera Tracking, Hand-off and Display LDRD 158819 Final Report

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

Anderson, Robert J.

2014-10-01

Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance-based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldn’t lead to more alarms, moremore » monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that take live video imagery from multiple video cameras, identify individual moving targets from the background imagery, and then display the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of current capability.« less

Multi-target camera tracking, hand-off and display LDRD 158819 final report

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

Anderson, Robert J.

2014-10-01

Modern security control rooms gather video and sensor feeds from tens to hundreds of cameras. Advanced camera analytics can detect motion from individual video streams and convert unexpected motion into alarms, but the interpretation of these alarms depends heavily upon human operators. Unfortunately, these operators can be overwhelmed when a large number of events happen simultaneously, or lulled into complacency due to frequent false alarms. This LDRD project has focused on improving video surveillance-based security systems by changing the fundamental focus from the cameras to the targets being tracked. If properly integrated, more cameras shouldn't lead to more alarms, moremore » monitors, more operators, and increased response latency but instead should lead to better information and more rapid response times. For the course of the LDRD we have been developing algorithms that take live video imagery from multiple video cameras, identifies individual moving targets from the background imagery, and then displays the results in a single 3D interactive video. In this document we summarize the work in developing this multi-camera, multi-target system, including lessons learned, tools developed, technologies explored, and a description of current capability.« less

Suppression of DS1 Phosphatidic Acid Phosphatase Confirms Resistance to Ralstonia solanacearum in Nicotiana benthamiana

PubMed Central

Nakano, Masahito; Nishihara, Masahiro; Yoshioka, Hirofumi; Takahashi, Hirotaka; Sawasaki, Tatsuya; Ohnishi, Kouhei; Hikichi, Yasufumi; Kiba, Akinori

2013-01-01

Nicotiana benthamiana is susceptible to Ralstonia solanacearum. To analyze molecular mechanisms for disease susceptibility, we screened a gene-silenced plant showing resistance to R. solanacearum, designated as DS1 (Disease suppression 1). The deduced amino acid sequence of DS1 cDNA encoded a phosphatidic acid phosphatase (PAP) 2. DS1 expression was induced by infection with a virulent strain of R. solanacearum in an hrp-gene-dependent manner. DS1 rescued growth defects of the temperature-sensitive ∆lpp1∆dpp1∆pah1 mutant yeast. Recombinant DS1 protein showed Mg2+-independent PAP activity. DS1 plants showed reduced PAP activity and increased phosphatidic acid (PA) content. After inoculation with R. solanacearum, DS1 plants showed accelerated cell death, over-accumulation of reactive oxygen species (ROS), and hyper-induction of PR-4 expression. In contrast, DS1-overexpressing tobacco plants showed reduced PA content, greater susceptibility to R. solanacearum, and reduced ROS production and PR-4 expression. The DS1 phenotype was partially compromised in the plants in which both DS1 and NbCoi1 or DS1 and NbrbohB were silenced. These results show that DS1 PAP may affect plant immune responses related to ROS and JA cascades via regulation of PA levels. Suppression of DS1 function or DS1 expression could rapidly activate plant defenses to achieve effective resistance against Ralstonia solanacearum. PMID:24073238

SMART-DS: Synthetic Models for Advanced, Realistic Testing: Distribution

Science.gov Websites

statistical summary of the U.S. distribution systems World-class, high spatial/temporal resolution of solar Systems and Scenarios | Grid Modernization | NREL SMART-DS: Synthetic Models for Advanced , Realistic Testing: Distribution Systems and Scenarios SMART-DS: Synthetic Models for Advanced, Realistic

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35

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

Leung, Daisy W.; Prins, Kathleen C.; Borek, Dominika M.

2010-03-12

Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also importantmore » for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.« less

Loop-mediated isothermal amplification (LAMP) assay for speedy diagnosis of tubercular lymphadenitis: The multi-targeted 60-minute approach.

PubMed

Sharma, Megha; Sharma, Kusum; Sharma, Aman; Gupta, Nalini; Rajwanshi, Arvind

2016-09-01

Tuberculous lymphadenitis (TBLA), the most common presentation of tuberculosis, poses a significant diagnostic challenge in the developing countries. Timely, accurate and cost-effective diagnosis can decrease the high morbidity associated with TBLA especially in resource-poor high-endemic regions. The loop-mediated isothermal amplification assay (LAMP), using two targets, was evaluated for the diagnosis of TBLA. LAMP assay using 3 sets of primers (each for IS6110 and MPB64) was performed on 170 fine needle aspiration samples (85 confirmed, 35 suspected, 50 control cases of TBLA). Results were compared against IS6110 PCR, cytology, culture and smear. The overall sensitivity and specificity of LAMP assay, using multi-targeted approach, was 90% and 100% respectively in diagnosing TBLA. The sensitivity of multi-targeted LAMP, only MPB64 LAMP, only IS6110 LAMP and IS6110 PCR was 91.7%, 89.4%, 84.7% and 75.2%, respectively among confirmed cases and 85.7%, 77.1%, 68.5% and 60%, respectively among suspected cases of TBLA. Additional 12/120 (10%) cases were detected using multi-targeted method. The multi-targeted LAMP, with its speedy and reliable results, is a potential diagnostic test for TBLA in low-resource countries. Copyright © 2016 Elsevier Ltd. All rights reserved.

The research of multi-frame target recognition based on laser active imaging

NASA Astrophysics Data System (ADS)

Wang, Can-jin; Sun, Tao; Wang, Tin-feng; Chen, Juan

2013-09-01

Laser active imaging is fit to conditions such as no difference in temperature between target and background, pitch-black night, bad visibility. Also it can be used to detect a faint target in long range or small target in deep space, which has advantage of high definition and good contrast. In one word, it is immune to environment. However, due to the affect of long distance, limited laser energy and atmospheric backscatter, it is impossible to illuminate the whole scene at the same time. It means that the target in every single frame is unevenly or partly illuminated, which make the recognition more difficult. At the same time the speckle noise which is common in laser active imaging blurs the images . In this paper we do some research on laser active imaging and propose a new target recognition method based on multi-frame images . Firstly, multi pulses of laser is used to obtain sub-images for different parts of scene. A denoising method combined homomorphic filter with wavelet domain SURE is used to suppress speckle noise. And blind deconvolution is introduced to obtain low-noise and clear sub-images. Then these sub-images are registered and stitched to combine a completely and uniformly illuminated scene image. After that, a new target recognition method based on contour moments is proposed. Firstly, canny operator is used to obtain contours. For each contour, seven invariant Hu moments are calculated to generate the feature vectors. At last the feature vectors are input into double hidden layers BP neural network for classification . Experiments results indicate that the proposed algorithm could achieve a high recognition rate and satisfactory real-time performance for laser active imaging.

A High Performance Computing Study of a Scalable FISST-Based Approach to Multi-Target, Multi-Sensor Tracking

NASA Astrophysics Data System (ADS)

Hussein, I.; Wilkins, M.; Roscoe, C.; Faber, W.; Chakravorty, S.; Schumacher, P.

2016-09-01

Finite Set Statistics (FISST) is a rigorous Bayesian multi-hypothesis management tool for the joint detection, classification and tracking of multi-sensor, multi-object systems. Implicit within the approach are solutions to the data association and target label-tracking problems. The full FISST filtering equations, however, are intractable. While FISST-based methods such as the PHD and CPHD filters are tractable, they require heavy moment approximations to the full FISST equations that result in a significant loss of information contained in the collected data. In this paper, we review Smart Sampling Markov Chain Monte Carlo (SSMCMC) that enables FISST to be tractable while avoiding moment approximations. We study the effect of tuning key SSMCMC parameters on tracking quality and computation time. The study is performed on a representative space object catalog with varying numbers of RSOs. The solution is implemented in the Scala computing language at the Maui High Performance Computing Center (MHPCC) facility.

Hyperthyroidism in a population with Down syndrome (DS).

PubMed

Goday-Arno, Alberto; Cerda-Esteva, Mariaina; Flores-Le-Roux, Juana Antonia; Chillaron-Jordan, Juan José; Corretger, Josep Maria; Cano-Pérez, Juan Francisco

2009-07-01

Thyroid disorders are frequent in patients with Down syndrome (DS). It is well-known that the prevalence of hypothyroidism is high but data on hyperthyroidism are scarce. To assess the prevalence, aetiology, clinical characteristics, evolution and treatment of hyperthyroidism in a population with DS attending a specialized medical centre. Data were gathered by systematic review of 1832 medical records from the Catalan DS Foundation, in Spain, registered between January 1991 and February 2006. Patients with the diagnosis of hyperthyroidism were identified and data on clinical features, physical examination, laboratory and imaging tests, treatment and evolution were collected. Twelve patients with hyperthyroidism were recorded (6.5 cases/1000 patients with DS). There were 5 males and 7 females, with a mean age at diagnosis of 16.8 years. The most common presenting symptoms were decreased heat tolerance, sweating, increased irritability and weight loss. All patients had diffuse goitre at physical examination and two patients presented with exophthalmia. Clinical diagnosis was confirmed biochemically. Thyroid-stimulating immunoglobulin levels were raised (mean 128.1 U/l) and imaging tests confirmed the diagnosis of Graves' disease in all cases. Patients started treatment with carbimazole at diagnosis and after a mean period of 40 months without clinical remission, they required definitive therapy with radioactive iodine. Subjects developed hypothyroidism after radio-iodine therapy and replacement therapy with levothyroxine was necessary. Hyperthyroidism is more prevalent in patients with DS than in the general population and has no gender predominance. It is caused mainly by Graves' disease. Anti-thyroid drugs were not effective in achieving remission and radioactive iodine as a definitive treatment was required in all cases.

The best management of SuDS treatment trains: a holistic approach.

PubMed

Bastien, Nicolas; Arthur, Scott; Wallis, Stephen; Scholz, Miklas

2010-01-01

The use of Sustainable Drainage Systems (SuDS) or Best Management Practice (BMP) is becoming increasingly common. However, rather than adopting the preferred "treatment train" implementation, many developments opt for end of pipe control ponds. This paper discusses the use of SuDS in series to form treatment trains and compares their potential performance and effectiveness with end of pipe solutions. Land-use, site and catchment characteristics have been used alongside up-to-date guidance, Infoworks CS and MUSIC to determine whole-life-costs, land-take, water quality and water quantity for different SuDS combinations. The results presented show that the use of a treatment train allows approaches differing from the traditional use of single SuDS, either source or "end of pipe", to be proposed to treat and attenuate runoff. The outcome is a more flexible solution where the footprint allocated to SuDS, costs and water quality can be managed differently to satisfy more efficiently the holistically stakeholders' objectives.

Study of Cabibbo suppressed decays of the Ds+ charmed-strange meson involving a KS0

NASA Astrophysics Data System (ADS)

Link, J. M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Castromonte, C.; Machado, A. A.; Magnin, J.; Massafferri, A.; de Miranda, J. M.; Pepe, I. M.; Polycarpo, E.; Dos Reis, A. C.; Carrillo, S.; Casimiro, E.; Cuautle, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J. P.; Frisullo, V.; O'Reilly, B.; Segoni, I.; Stenson, K.; Tucker, R. S.; Butler, J. N.; Cheung, H. W. K.; Chiodini, G.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Wang, M.; Benussi, L.; Bianco, S.; Fabbri, F. L.; Zallo, A.; Reyes, M.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; Cerutti, A.; D'Angelo, P.; Dicorato, M.; Dini, P.; Edera, L.; Erba, S.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport, T. F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Lopes Pegna, D.; Merlo, M. M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Göbel, C.; Otalora, J.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Paris, A.; Quinones, J.; Ramirez, J. E.; Zhang, Y.; Wilson, J. R.; Handler, T.; Mitchell, R.; Engh, D.; Hosack, M.; Johns, W. E.; Luiggi, E.; Nehring, M.; Sheldon, P. D.; Vaandering, E. W.; Webster, M.; Sheaff, M.; Focus Collaboration

2008-02-01

We study the decay of Ds+ mesons into final states involving a KS0 and report the discovery of Cabibbo suppressed decay modes Ds+ →KS0π-π+π+ (179 ± 36 events) and Ds+ →KS0π+ (113 ± 26 events). The branching fraction ratios for the new modes are Γ (Ds+ →KS0π-π+π+)/Γ (Ds+ →KS0K-π+π+) = 0.18 ± 0.04 ± 0.05 and Γ (Ds+ →KS0π+)/Γ (Ds+ →KS0K+) = 0.104 ± 0.024 ± 0.014.

Study of Cabibbo suppressed decays of the Ds+ charmed-strange meson involving a KS0

NASA Astrophysics Data System (ADS)

FOCUS Collaboration; Link, J. M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Castromonte, C.; Machado, A. A.; Magnin, J.; Massafferri, A.; de Miranda, J. M.; Pepe, I. M.; Polycarpo, E.; Dos Reis, A. C.; Carrillo, S.; Casimiro, E.; Cuautle, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Agostino, L.; Cinquini, L.; Cumalat, J. P.; Frisullo, V.; O'Reilly, B.; Segoni, I.; Stenson, K.; Tucker, R. S.; Butler, J. N.; Cheung, H. W. K.; Chiodini, G.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Wang, M.; Benussi, L.; Bianco, S.; Fabbri, F. L.; Zallo, A.; Reyes, M.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Kryemadhi, A.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Cho, K.; Park, H.; Alimonti, G.; Barberis, S.; Boschini, M.; Cerutti, A.; D'Angelo, P.; Dicorato, M.; Dini, P.; Edera, L.; Erba, S.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, S.; Davenport, T. F.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Lopes Pegna, D.; Merlo, M. M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Vitulo, P.; Göbel, C.; Otalora, J.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Paris, A.; Quinones, J.; Ramirez, J. E.; Zhang, Y.; Wilson, J. R.; Handler, T.; Mitchell, R.; Engh, D.; Hosack, M.; Johns, W. E.; Luiggi, E.; Nehring, M.; Sheldon, P. D.; Vaandering, E. W.; Webster, M.; Sheaff, M.

2008-02-01

We study the decay of Ds+ mesons into final states involving a KS0 and report the discovery of Cabibbo suppressed decay modes Ds+→KS0πππ (179±36 events) and Ds+→KS0π (113±26 events). The branching fraction ratios for the new modes are Γ(Ds+→KS0πππ)Γ(Ds+→KS0Kππ)=0.18±0.04±0.05 and Γ(Ds+→KS0π)Γ(Ds+→KS0K)=0.104±0.024±0.014.

Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem

PubMed Central

Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

2016-01-01

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design. PMID:27958331

Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem.

PubMed

Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

2016-12-13

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.

Titanium dioxide nanofiber-cotton targets for efficient multi-keV x-ray generation

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

Tanabe, Minoru; Nishimura, Hiroaki; Fujioka, Shinsuke

Multi-keV x-ray generation from low-density (27{+-}7 mg/cm{sup 3}) nanofiber-cotton targets composed of titanium dioxide has been investigated. The cotton targets were heated volumetrically and supersonically to a peak electron temperature of 2.3 keV, which is optimal to yield Ti K-shell x rays. Considerable enhancement of conversion efficiency [(3.7{+-}0.5)%] from incident laser energy into Ti K-shell x rays (4-6 keV band) was attained in comparison with that [(1.4{+-}0.9)%] for a planar Ti-foil target.

Correlation between CHA2DS2-VASc Score and Glaucoma Treatment and Prognosis.

PubMed

Pikkel, Yoav Y; Krebs, Daniel; Igal, Vadim; Sharabi-Nov, Adi; Epstein, Irena; Pikkel, Joseph

2018-01-01

To find if CHA 2 DS 2 -VASc scale can accurately predict the treatment, prognosis, and outcome for primary open-angle glaucoma (POAG). A survey of 250,000 patient years was taken, using the records of the Ophthalmology Department at Ziv Medical Center. Data was collected regarding the retinal nerve fiber layer (RNFL), visual field (VF), line of treatment (LOT) of glaucoma, and all the data needed to accurately calculate CHA 2 DS 2 -VASc score for each patient. Sixty-seven patients were included in the statistical analysis. The mean age was 72.5 years. The mean CHA 2 DS 2 -VASc score was 3.27 + -1.7. Positive Pearson's correlation coefficients were found for LOT and CHA 2 DS 2 -VASc score, 0.35, and for RNFL grade and CHA2DS2-VASc score, 0.37. The correlation was negative for RNFL width and CHA2DS2-VASc score, -0.35. CHA 2 DS 2 -VASc score was shown to be correlated with glaucoma. This correlation was manifested positively by the LOT needed to stop glaucoma progression, with higher CHA 2 DS 2 -VASc scores correlated with more aggressive treatment. Since glaucoma is a disease with a progressing nature, it is important to treat patients aggressively on one hand, while offering the most benign treatment as possible on the other hand. Modification of the CHA 2 DS 2 -VASc score could achieve an even higher correlation.

Optical fiber sources and transmission controls for multi-Tb/s systems

NASA Astrophysics Data System (ADS)

Nowak, George Adelbert

The accelerating demand for bandwidth capacity in backbone links of terrestrial communications systems is projected to exceed 1Tb/s by 2002. Lightwave carrier frequencies and fused-silica optical fibers provide the natural combination of high passband frequencies and low- loss medium to satisfy this evolving demand for bandwidth capacity. This thesis addresses three key technologies for enabling multi-Tb/s optical fiber communication systems. The first technology is a broadband source based on supercontinuum generation in optical fiber. Using a single modelocked laser with output pulsewidths of 0.5psec pulses, we generate in ~2m of dispersion-shifted fiber more that 200nm of spectral continuum in the vicinity of 1550nm that is flat to better than +/- 0.5 dB over more than 60nm. The short fiber length prevents degradation of timing jitter of the seed pulses and preserves coherence of the continuum by inhibiting environmental perturbations and mapping of random noise from the vicinity of the input pulse across the continuum. Through experiments and simulations, we find that the continuum characteristics result from 3rd order dispersion effects on higher-order soliton compression. We determine optimal fiber properties to provide desired continuum broadness and flatness for given input pulsewidth and energy conditions. The second technology is a novel delay-shifted nonlinear optical loop mirror (DS-NOLM) that performs a transmission control function by serving as an intensity filter and frequency compensator for <5psec soliton transmission systems. A theoretical and experimental study of the DS-NOLM as a transmission control element in a periodically amplified soliton transmission system is presented. We show that DS-NOLMs enable 4ps soliton transmission over 75km of standard dispersion fiber, with 25km spacing between amplifiers, by filtering the dispersive waves and compensating for Raman-induced soliton self-frequency shift. The third technology is all

dsRNA binding properties of RDE-4 and TRBP reflect their distinct roles in RNAi

PubMed Central

Parker, Greg S.; Maity, Tuhin Subhra; Bass, Brenda L.

2008-01-01

SUMMARY dsRNA binding proteins (dsRBPs) facilitate Dicer functions in RNAi. C. elegans RDE-4 facilitates cleavage of long dsRNA to siRNA, while human TRBP functions downstream to pass siRNA to RISC. We show that these distinct in vivo roles are reflected in in vitro binding properties. RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. These properties are mechanistically based in the fact that RDE-4 binds cooperatively, via contributions from multiple domains, while TRBP binds non-cooperatively. Our studies offer a paradigm for how dsRBPs, which are not sequence-specific, discern dsRNA length. Additionally, analyses of the ability of RDE-4 deletion constructs and RDE-4/TRBP chimeras to reconstitute Dicer activity suggest RDE-4 promotes activity using its dsRBM2 to bind dsRNA, its linker region to interact with Dicer, and its C-terminus for Dicer activation. PMID:18948111

Two-Way Gold Nanoparticle Label-Free Sensing of Specific Sequence and Small Molecule Targets Using Switchable Concatemers.

PubMed

Zhu, Longjiao; Shao, Xiangli; Luo, Yunbo; Huang, Kunlung; Xu, Wentao

2017-05-19

A two-way colorimetric biosensor based on unmodified gold nanoparticles (GNPs) and a switchable double-stranded DNA (dsDNA) concatemer have been demonstrated. Two hairpin probes (H1 and H2) were first designed that provided the fuels to assemble the dsDNA concatemers via hybridization chain reaction (HCR). A functional hairpin (FH) was rationally designed to recognize the target sequences. All the hairpins contained a single-stranded DNA (ssDNA) loop and sticky end to prevent GNPs from salt-induced aggregation. In the presence of target sequence, the capture probe blocked in the FH recognizes the target to form a duplex DNA, which causes the release of the initiator probe by FH conformational change. This process then starts the alternate-opening of H1 and H2 through HCR, and dsDNA concatemers grow from the target sequence. As a result, unmodified GNPs undergo salt-induced aggregation because the formed dsDNA concatemers are stiffer and provide less stabilization. A light purple-to-blue color variation was observed in the bulk solution, termed the light-off sensing way. Furthermore, H1 ingeniously inserted an aptamer sequence to generate dsDNA concatemers with multiple small molecule binding sites. In the presence of small molecule targets, concatemers can be disassembled into mixtures with ssDNA sticky ends. A blue-to-purple reverse color variation was observed due to the regeneration of the ssDNA, termed the light-on way. The two-way biosensor can detect both nucleic acids and small molecule targets with one sensing device. This switchable sensing element is label-free, enzyme-free, and sophisticated-instrumentation-free. The detection limits of both targets were below nanomolar.

Differential Genetic Associations for Systemic Lupus Erythematosus Based on Anti–dsDNA Autoantibody Production

PubMed Central

Chung, Sharon A.; Taylor, Kimberly E.; Graham, Robert R.; Nititham, Joanne; Lee, Annette T.; Ortmann, Ward A.; Jacob, Chaim O.; Alarcón-Riquelme, Marta E.; Tsao, Betty P.; Harley, John B.; Gaffney, Patrick M.; Moser, Kathy L.; Petri, Michelle; Demirci, F. Yesim; Kamboh, M. Ilyas; Manzi, Susan; Gregersen, Peter K.; Langefeld, Carl D.; Behrens, Timothy W.; Criswell, Lindsey A.

2011-01-01

Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA – SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA – SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA – SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA – SLE. PMID

Absolute Measurement of Hadronic Branching Fractions of the Ds+ Meson

NASA Astrophysics Data System (ADS)

Alexander, J. P.; Berkelman, K.; Cassel, D. G.; Duboscq, J. E.; Ehrlich, R.; Fields, L.; Gibbons, L.; Gray, R.; Gray, S. W.; Hartill, D. L.; Heltsley, B. K.; Hertz, D.; Jones, C. D.; Kandaswamy, J.; Kreinick, D. L.; Kuznetsov, V. E.; Mahlke-Krüger, H.; Mohapatra, D.; Onyisi, P. U. E.; Patterson, J. R.; Peterson, D.; Riley, D.; Ryd, A.; Sadoff, A. J.; Shi, X.; Stroiney, S.; Sun, W. M.; Wilksen, T.; Athar, S. B.; Patel, R.; Yelton, J.; Rubin, P.; Eisenstein, B. I.; Karliner, I.; Mehrabyan, S.; Lowrey, N.; Selen, M.; White, E. J.; Wiss, J.; Mitchell, R. E.; Shepherd, M. R.; Besson, D.; Pedlar, T. K.; Cronin-Hennessy, D.; Gao, K. Y.; Hietala, J.; Kubota, Y.; Klein, T.; Lang, B. W.; Poling, R.; Scott, A. W.; Zweber, P.; Dobbs, S.; Metreveli, Z.; Seth, K. K.; Tomaradze, A.; Libby, J.; Powell, A.; Wilkinson, G.; Ecklund, K. M.; Love, W.; Savinov, V.; Lopez, A.; Mendez, H.; Ramirez, J.; Ge, J. Y.; Miller, D. H.; Sanghi, B.; Shipsey, I. P. J.; Xin, B.; Adams, G. S.; Anderson, M.; Cummings, J. P.; Danko, I.; Hu, D.; Moziak, B.; Napolitano, J.; He, Q.; Insler, J.; Muramatsu, H.; Park, C. S.; Thorndike, E. H.; Yang, F.; Artuso, M.; Blusk, S.; Khalil, S.; Li, J.; Mountain, R.; Nisar, S.; Randrianarivony, K.; Sultana, N.; Skwarnicki, T.; Stone, S.; Wang, J. C.; Zhang, L. M.; Bonvicini, G.; Cinabro, D.; Dubrovin, M.; Lincoln, A.; Rademacker, J.; Asner, D. M.; Edwards, K. W.; Naik, P.; Briere, R. A.; Ferguson, T.; Tatishvili, G.; Vogel, H.; Watkins, M. E.; Rosner, J. L.

2008-04-01

The branching fractions of Ds± meson decays serve to normalize many measurements of processes involving charm quarks. Using 298pb-1 of e+e- collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight Ds± decays with a double tag technique. In particular we determine the branching fraction B(Ds+→K-K+π+)=(5.50±0.23±0.16)%, where the uncertainties are statistical and systematic, respectively. We also provide partial branching fractions for kinematic subsets of the K-K+π+ decay mode.

Characterization of a hybrid target multi-keV x-ray source by a multi-parameter statistical analysis of titanium K-shell emission

DOE PAGES

Primout, M.; Babonneau, D.; Jacquet, L.; ...

2015-11-10

We studied the titanium K-shell emission spectra from multi-keV x-ray source experiments with hybrid targets on the OMEGA laser facility. Using the collisional-radiative TRANSPEC code, dedicated to K-shell spectroscopy, we reproduced the main features of the detailed spectra measured with the time-resolved MSPEC spectrometer. We developed a general method to infer the N e, T e and T i characteristics of the target plasma from the spectral analysis (ratio of integrated Lyman-α to Helium-α in-band emission and the peak amplitude of individual line ratios) of the multi-keV x-ray emission. Finally, these thermodynamic conditions are compared to those calculated independently bymore » the radiation-hydrodynamics transport code FCI2.« less

Ablation mass features in multi-pulses femtosecond laser ablate molybdenum target

NASA Astrophysics Data System (ADS)

Zhao, Dongye; Gierse, Niels; Wegner, Julian; Pretzler, Georg; Oelmann, Jannis; Brezinsek, Sebastijan; Liang, Yunfeng; Neubauer, Olaf; Rasinski, Marcin; Linsmeier, Christian; Ding, Hongbin

2018-03-01

In this study, the ablation mass features related to reflectivity of bulk Molybdenum (Mo) were investigated by a Ti: Sa 6 fs laser pulse at central wavelength 790 nm. The ablated mass removal was determined using Confocal Microscopy (CM) technique. The surface reflectivity was calibrated and measured by a Lambda 950 spectrophotometer as well as a CCD camera during laser ablation. The ablation mass loss per pulse increase with the increasing of laser shots, meanwhile the surface reflectivity decrease. The multi-pulses (100 shots) ablation threshold of Mo was determined to be 0.15 J/cm2. The incubation coefficient was estimated as 0.835. The reflectivity change of the Mo target surface following multi-pulses laser ablation were studied as a function of laser ablation shots at various laser fluences from 1.07 J/cm2 to 36.23 J/cm2. The results of measured reflectivity indicate that surface reflectivity of Mo target has a significant decline in the first 3-laser pulses at the various fluences. These results are important for developing a quantitative analysis model for laser induced ablation and laser induced breakdown spectroscopy for the first wall diagnosis of EAST tokamak.

Larval application of sodium channel homologous dsRNA restores pyrethroid insecticide susceptibility in a resistant adult mosquito population.

PubMed

Bona, Ana Caroline Dalla; Chitolina, Rodrigo Faitta; Fermino, Marise Lopes; de Castro Poncio, Lisiane; Weiss, Avital; Lima, José Bento Pereira; Paldi, Nitzan; Bernardes, Emerson Soares; Henen, Jonathan; Maori, Eyal

2016-07-14

Mosquitoes host and pass on to humans a variety of disease-causing pathogens such as infectious viruses and other parasitic microorganisms. The emergence and spread of insecticide resistance is threatening the effectiveness of current control measures for common mosquito vector borne diseases, such as malaria, dengue and Zika. Therefore, the emerging resistance to the widely used pyrethroid insecticides is an alarming problem for public health. Herein we demonstrated the use of RNA interference (RNAi) to increase susceptibility of adult mosquitoes to a widely used pyrethroid insecticide. Experiments were performed on a field-collected pyrethroid resistant strain of Ae. aegypti (Rio de Janeiro; RJ). Larvae from the resistant Ae. aegypti population were soaked with double-stranded RNAs (dsRNAs) that correspond either to voltage-gate sodium channel (VGSC), P-glycoprotein, or P450 detoxification genes and reared to adulthood. Adult mortality rates in the presence of various Deltamethrin pyrethroid concentrations were used to assess mosquito insecticide susceptibility. We characterized the RJ Ae. aegypti strain with regard to its level of resistance to a pyrethroid insecticide and found that it was approximately 6 times more resistant to Deltamethrin compared to the laboratory Rockefeller strain. The RJ strain displayed a higher frequency of Val1016Ile and Phe1534Cys substitutions of the VGSC gene. The resistant strain also displayed a higher basal expression level of VGSC compared to the Rockefeller strain. When dsRNA-treated mosquitoes were subjected to a standard pyrethroid contact bioassay, only dsRNA targeting VGSC increased the adult mortality of the pyrethroid resistant strain. The dsRNA treatment proved effective in increasing adult mosquito susceptibility over a range of pyrethroid concentrations and these results were associated with dsRNA-specific small interfering RNAs in treated adults, and the corresponding specific down regulation of VGSC gene expression

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding.

PubMed

Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D; Heywood, Sam; Humphreys, David P

2016-10-01

An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG.

Fab-dsFv: A bispecific antibody format with extended serum half-life through albumin binding

PubMed Central

Davé, Emma; Adams, Ralph; Zaccheo, Oliver; Carrington, Bruce; Compson, Joanne E.; Dugdale, Sarah; Airey, Michael; Malcolm, Sarah; Hailu, Hanna; Wild, Gavin; Turner, Alison; Heads, James; Sarkar, Kaushik; Ventom, Andrew; Marshall, Diane; Jairaj, Mark; Kopotsha, Tim; Christodoulou, Louis; Zamacona, Miren; Lawson, Alastair D.; Heywood, Sam; Humphreys, David P.

2016-01-01

ABSTRACT An antibody format, termed Fab-dsFv, has been designed for clinical indications that require monovalent target binding in the absence of direct Fc receptor (FcR) binding while retaining substantial serum presence. The variable fragment (Fv) domain of a humanized albumin-binding antibody was fused to the C-termini of Fab constant domains, such that the VL and VH domains were individually connected to the Cκ and CH1 domains by peptide linkers, respectively. The anti-albumin Fv was selected for properties thought to be desirable to ensure a durable serum half-life mediated via FcRn. The Fv domain was further stabilized by an inter-domain disulfide bond. The bispecific format was shown to be thermodynamically and biophysically stable, and retained good affinity and efficacy to both antigens simultaneously. In in vivo studies, the serum half-life of Fab-dsFv, 2.6 d in mice and 7.9 d in cynomolgus monkeys, was equivalent to Fab'-PEG. PMID:27532598

Observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ).

PubMed

Sanchez, P del Amo; Lees, J P; Poireau, V; Prencipe, E; Tisserand, V; Garra Tico, J; Grauges, E; Martinelli, M; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Battaglia, M; Brown, D N; Hooberman, B; Kerth, L T; Kolomensky, Yu G; Lynch, G; Osipenkov, I L; Tanabe, T; Hawkes, C M; Watson, A T; Koch, H; Schroeder, T; Asgeirsson, D J; Hearty, C; Mattison, T S; McKenna, J A; Khan, A; Randle-Conde, A; Blinov, V E; Buzykaev, A R; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Yushkov, A N; Bondioli, M; Curry, S; Kirkby, D; Lankford, A J; Mandelkern, M; Martin, E C; Stoker, D P; Atmacan, H; Gary, J W; Liu, F; Long, O; Vitug, G M; Campagnari, C; Hong, T M; Kovalskyi, D; Richman, J D; Eisner, A M; Heusch, C A; Kroseberg, J; Lockman, W S; Martinez, A J; Schalk, T; Schumm, B A; Seiden, A; Winstrom, L O; Cheng, C H; Doll, D A; Echenard, B; Hitlin, D G; Ongmongkolkul, P; Porter, F C; Rakitin, A Y; Andreassen, R; Dubrovin, M S; Mancinelli, G; Meadows, B T; Sokoloff, M D; Bloom, P C; Ford, W T; Gaz, A; Nagel, M; Nauenberg, U; Smith, J G; Wagner, S R; Ayad, R; Toki, W H; Jasper, H; Karbach, T M; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Kobel, M J; Schubert, K R; Schwierz, R; Bernard, D; Verderi, M; Clark, P J; Playfer, S; Watson, J E; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Fioravanti, E; Franchini, P; Luppi, E; Munerato, M; Negrini, M; Petrella, A; Piemontese, L; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Nicolaci, M; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Contri, R; Guido, E; Lo Vetere, M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Tosi, S; Bhuyan, B; Prasad, V; Lee, C L; Morii, M; Adametz, A; Marks, J; Schenk, S; Uwer, U; Bernlochner, F U; Ebert, M; Lacker, H M; Lueck, T; Volk, A; Dauncey, P D; Tibbetts, M; Behera, P K; Mallik, U; Chen, C; Cochran, J; Crawley, H B; Dong, L; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Arnaud, N; Davier, M; Derkach, D; da Costa, J Firmino; Grosdidier, G; Le Diberder, F; Lutz, A M; Malaescu, B; Perez, A; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, L; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Chavez, C A; Coleman, J P; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Touramanis, C; Bevan, A J; Di Lodovico, F; Sacco, R; Sigamani, M; Cowan, G; Paramesvaran, S; Wren, A C; Brown, D N; Davis, C L; Denig, A G; Fritsch, M; Gradl, W; Hafner, A; Alwyn, K E; Bailey, D; Barlow, R J; Jackson, G; Lafferty, G D; West, T J; Anderson, J; Cenci, R; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Dallapiccola, C; Salvati, E; Cowan, R; Dujmic, D; Fisher, P H; Sciolla, G; Zhao, M; Lindemann, D; Patel, P M; Robertson, S H; Schram, M; Biassoni, P; Lazzaro, A; Lombardo, V; Palombo, F; Stracka, S; Cremaldi, L; Godang, R; Kroeger, R; Sonnek, P; Summers, D J; Nguyen, X; Simard, M; Taras, P; De Nardo, G; Monorchio, D; Onorato, G; Sciacca, C; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; LoSecco, J M; Wang, W F; Corwin, L A; Honscheid, K; Kass, R; Morris, J P; Rahimi, A M; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Castelli, G; Feltresi, E; Gagliardi, N; Margoni, M; Morandin, M; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Ben-Haim, E; Bonneaud, G R; Briand, H; Calderini, G; Chauveau, J; Hamon, O; Leruste, Ph; Marchiori, G; Ocariz, J; Prendki, J; Sitt, S; Biasini, M; Manoni, E; Rossi, A; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Casarosa, G; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Pegna, D Lopes; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Anulli, F; Baracchini, E; Cavoto, G; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Li Gioi, L; Mazzoni, M A; Piredda, G; Renga, F; Hartmann, T; Leddig, T; Schröder, H; Waldi, R; Adye, T; Franek, B; Olaiya, E O; Wilson, F F; Emery, S; de Monchenault, G Hamel; Vasseur, G; Yèche, Ch; Zito, M; Allen, M T; Aston, D; Bard, D J; Bartoldus, R; Benitez, J F; Cartaro, C; Convery, M R; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Sevilla, M Franco; Fulsom, B G; Gabareen, A M; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Lindquist, B; Luitz, S; Luth, V; Lynch, H L; MacFarlane, D B; Marsiske, H; Muller, D R; Neal, H; Nelson, S; O'Grady, C P; Ofte, I; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Santoro, V; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Sun, S; Suzuki, K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; West, C A; Wisniewski, W J; Wittgen, M; Wright, D H; Wulsin, H W; Yarritu, A K; Young, C C; Ziegler, V; Chen, X R; Park, W; Purohit, M V; White, R M; Wilson, J R; Sekula, S J; Bellis, M; Burchat, P R; Edwards, A J; Miyashita, T S; Ahmed, S; Alam, M S; Ernst, J A; Pan, B; Saeed, M A; Zain, S B; Guttman, N; Soffer, A; Lund, P; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Wray, B C; Izen, J M; Lou, X C; Bianchi, F; Gamba, D; Pelliccioni, M; Bomben, M; Lanceri, L; Vitale, L; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Choi, H H F; Hamano, K; King, G J; Kowalewski, R; Lewczuk, M J; Nugent, I M; Roney, J M; Sobie, R J; Gershon, T J; Harrison, P F; Latham, T E; Puccio, E M T; Band, H R; Dasu, S; Flood, K T; Pan, Y; Prepost, R; Vuosalo, C O; Wu, S L

2011-07-22

We report the observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) based on 342  fb(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B- → D(s)((*)+) K- ℓ- ν(ℓ)) = [6.13(-1.03)(+1.04)(stat)±0.43(syst)±0.51(B(D(s)))]×10(-4), where the last error reflects the limited knowledge of the D(s) branching fractions.

A Charrelation Matrix-Based Blind Adaptive Detector for DS-CDMA Systems

PubMed Central

Luo, Zhongqiang; Zhu, Lidong

2015-01-01

In this paper, a blind adaptive detector is proposed for blind separation of user signals and blind estimation of spreading sequences in DS-CDMA systems. The blind separation scheme exploits a charrelation matrix for simple computation and effective extraction of information from observation signal samples. The system model of DS-CDMA signals is modeled as a blind separation framework. The unknown user information and spreading sequence of DS-CDMA systems can be estimated only from the sampled observation signals. Theoretical analysis and simulation results show that the improved performance of the proposed algorithm in comparison with the existing conventional algorithms used in DS-CDMA systems. Especially, the proposed scheme is suitable for when the number of observation samples is less and the signal to noise ratio (SNR) is low. PMID:26287209

A Charrelation Matrix-Based Blind Adaptive Detector for DS-CDMA Systems.

PubMed

Luo, Zhongqiang; Zhu, Lidong

2015-08-14

In this paper, a blind adaptive detector is proposed for blind separation of user signals and blind estimation of spreading sequences in DS-CDMA systems. The blind separation scheme exploits a charrelation matrix for simple computation and effective extraction of information from observation signal samples. The system model of DS-CDMA signals is modeled as a blind separation framework. The unknown user information and spreading sequence of DS-CDMA systems can be estimated only from the sampled observation signals. Theoretical analysis and simulation results show that the improved performance of the proposed algorithm in comparison with the existing conventional algorithms used in DS-CDMA systems. Especially, the proposed scheme is suitable for when the number of observation samples is less and the signal to noise ratio (SNR) is low.

Delivery of dsRNA through topical feeding for RNA interference in the citrus sap piercing-sucking hemipteran, Diaphorina citri.

PubMed

Killiny, Nabil; Kishk, Abdelaziz

2017-06-01

RNA interference (RNAi) is a powerful means to study functional genomics in insects. The delivery of dsRNA is a challenging step in the development of RNAi assay. Here, we describe a new delivery method to increase the effectiveness of RNAi in the Asian citrus psyllid Diaphorina citri. Bromophenol blue droplets were topically applied to fifth instar nymphs and adults on the ventral side of the thorax between the three pairs of legs. In addition to video recordings that showed sucking of the bromophenol blue by the stylets, dissected guts turned blue indicating that the uptake was through feeding. Thus, we called the method topical feeding. We targeted the abnormal wing disc gene (awd), also called nucleoside diphosphate kinase (NDPK), as a reporter gene to prove the uptake of dsRNA via this method of delivery. Our results showed that dsRNA-awd caused reduction of awd expression and nymph mortality. Survival and lifespan of adults emerged from treated nymphs and treated adults were affected. Silencing awd caused wing malformation in the adults emerged from treated nymphs. Topical feeding as a delivery of dsRNA is highly efficient for both nymphs and adults. The described method could be used to increase the efficiency of RNAi in D. citri and other sap piercing-sucking hemipterans. © 2017 Wiley Periodicals, Inc.

Identifying natural compounds as multi-target-directed ligands against Alzheimer's disease: an in silico approach.

PubMed

Ambure, Pravin; Bhat, Jyotsna; Puzyn, Tomasz; Roy, Kunal

2018-04-23

Alzheimer's disease (AD) is a multi-factorial disease, which can be simply outlined as an irreversible and progressive neurodegenerative disorder with an unclear root cause. It is a major cause of dementia in old aged people. In the present study, utilizing the structural and biological activity information of ligands for five important and mostly studied vital targets (i.e. cyclin-dependant kinase 5, β-secretase, monoamine oxidase B, glycogen synthase kinase 3β, acetylcholinesterase) that are believed to be effective against AD, we have developed five classification models using linear discriminant analysis (LDA) technique. Considering the importance of data curation, we have given more attention towards the chemical and biological data curation, which is a difficult task especially in case of big data-sets. Thus, to ease the curation process we have designed Konstanz Information Miner (KNIME) workflows, which are made available at http://teqip.jdvu.ac.in/QSAR_Tools/ . The developed models were appropriately validated based on the predictions for experiment derived data from test sets, as well as true external set compounds including known multi-target compounds. The domain of applicability for each classification model was checked based on a confidence estimation approach. Further, these validated models were employed for screening of natural compounds collected from the InterBioScreen natural database ( https://www.ibscreen.com/natural-compounds ). Further, the natural compounds that were categorized as 'actives' in at least two classification models out of five developed models were considered as multi-target leads, and these compounds were further screened using the drug-like filter, molecular docking technique and then thoroughly analyzed using molecular dynamics studies. Finally, the most potential multi-target natural compounds against AD are suggested.

No-insulation multi-width winding technique for high temperature superconducting magnet.

PubMed

Hahn, Seungyong; Kim, Youngjae; Keun Park, Dong; Kim, Kwangmin; Voccio, John P; Bascuñán, Juan; Iwasa, Yukikazu

2013-10-21

We present a No-Insulation ( NI ) Multi-Width ( MW ) winding technique for an HTS (high temperature superconductor) magnet consisting of double-pancake (DP) coils. The NI enables an HTS magnet self-protecting and the MW minimizes the detrimental anisotropy in current-carrying capacity of HTS tape by assigning tapes of multiple widths to DP coils within a stack, widest tape to the top and bottom sections and the narrowest in the midplane section. This paper presents fabrication and test results of an NI-MW HTS magnet and demonstrates the unique features of the NI-MW technique: self-protecting and enhanced field performance, unattainable with the conventional technique.

No-insulation multi-width winding technique for high temperature superconducting magnet

PubMed Central

Hahn, Seungyong; Kim, Youngjae; Keun Park, Dong; Kim, Kwangmin; Voccio, John P.; Bascuñán, Juan; Iwasa, Yukikazu

2013-01-01

We present a No-Insulation (NI) Multi-Width (MW) winding technique for an HTS (high temperature superconductor) magnet consisting of double-pancake (DP) coils. The NI enables an HTS magnet self-protecting and the MW minimizes the detrimental anisotropy in current-carrying capacity of HTS tape by assigning tapes of multiple widths to DP coils within a stack, widest tape to the top and bottom sections and the narrowest in the midplane section. This paper presents fabrication and test results of an NI-MW HTS magnet and demonstrates the unique features of the NI-MW technique: self-protecting and enhanced field performance, unattainable with the conventional technique. PMID:24255549

Double-stranded RNA targeting calmodulin reveals a potential target for pest management of Nilaparvata lugens.

PubMed

Wang, Weixia; Wan, Pinjun; Lai, Fengxiang; Zhu, Tingheng; Fu, Qiang

2018-07-01

Calmodulin (CaM) is an essential protein in cellular activity and plays important roles in many processes in insect development. RNA interference (RNAi) has been hypothesized to be a promising method for pest control. CaM is a good candidate for RNAi target. However, the sequence and function of CaM in Nilaparvata lugens are unknown. Furthermore, the double-stranded RNA (dsRNA) target to CaM gene in pest control is still unavailable. In the present study, two alternatively spliced variants of CaM transcripts, designated NlCaM1 and NlCaM2, were cloned from N. lugens. The two cDNA sequences exhibited 100% identity to each other in the open reading frame (ORF), and only differed in the 3' untranslated region (UTR). NlCaM including NlCaM1 and NlCaM2 mRNA was detectable in all developmental stages and tissues of N. lugens, with significantly increased expression in the salivary glands. Knockdown of NlCaM expression by RNAi with different dsRNAs led to an inability to molt properly, increased mortality, which ranged from 49.7 to 92.5%, impacted development of the ovaries and led to female infertility. There were no significant reductions in the transcript levels of vitellogenin and its receptor or in the total vitellogenin protein level relative to the control group. However, a significant reduction in vitellogenin protein was detected in ovaries injected with dsNlCaM. In addition, a specific dsRNA of NlCaM for control of N. lugens was designed and tested. NlCaM plays important roles mainly in nymph development and uptake of vitellogenin by ovaries in vitellogenesis in N. lugens. dsRNA derived from the less conserved 3'-UTR of NlCaM shows great potential for RNAi-based N. lugens management. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Inorganic nanocomposite films with polymer nanofillers made by the concurrent multi-beam multi-target pulsed laser deposition

NASA Astrophysics Data System (ADS)

Darwish, Abdalla M.; Sarkisov, Sergey S.; Mele, Paolo; Saini, Shrikant; Moore, Shaelynn; Bastian, Tyler; Dorlus, Wydglif; Zhang, Xiaodong; Koplitz, Brent

2017-08-01

We report on the new class of inorganic nanocomposite films with the inorganic phase hosting the polymer nanofillers made by the concurrent multi-beam multi-target pulsed laser deposition of the inorganic target material and matrix assisted pulsed laser evaporation of the polymer (MBMT-PLD/MAPLE). We used the exemplary nanocomposite thermoelectric films of aluminum-doped ZnO known as AZO with the nanofillers made of poly(methyl methacrylate) known as PMMA on various substrates such as SrTiO3, sapphire, fused silica, and polyimide. The AZO target was ablated with the second harmonic (532 nm) of the Nd:YAG Q-switched laser while PMMA was evaporated from its solution in chlorobenzene frozen in liquid nitrogen with the fundamental harmonic (1064 nm) of the same laser (50 Hz pulse repetition rate). The introduction of the polymer nanofillers increased the electrical conductivity of the nanocomposite films (possibly due to the carbonization of PMMA and the creation of additional channels of electric current) three times and reduced the thermal conductivity by 1.25 times as compared to the pure AZO films. Accordingly, the increase of the thermoelectric figure-of merit ZT would be 4 times. The best performance was observed for the sapphire substrates where the films were the most uniform. The results point to a huge potential of the optimization of a broad variety of optical, opto-electronic, and solar-power nanocomposite inorganic films by the controllable introduction of the polymer nanofillers using the MBMT-PLD/MAPLE method.

Quadriphase DS-CDMA wireless communication systems employing the generalized detector

NASA Astrophysics Data System (ADS)

Tuzlukov, Vyacheslav

2012-05-01

Probability of bit-error Per performance of asynchronous direct-sequence code-division multiple-access (DS-CDMA) wireless communication systems employing the generalized detector (GD) constructed based on the generalized approach to signal processing in noise is analyzed. The effects of pulse shaping, quadriphase or direct sequence quadriphase shift keying (DS-QPSK) spreading, aperiodic spreading sequences are considered in DS-CDMA based on GD and compared with the coherent Neyman-Pearson receiver. An exact Per expression and several approximations: one using the characterristic function method, a simplified expression for the improved Gaussian approximation (IGA) and the simplified improved Gaussian approximation are derived. Under conditions typically satisfied in practice and even with a small number of interferers, the standard Gaussian approximation (SGA) for the multiple-access interference component of the GD statistic and Per performance is shown to be accurate. Moreover, the IGA is shown to reduce to the SGA for pulses with zero excess bandwidth. Second, the GD Per performance of quadriphase DS-CDMA is shown to be superior to that of bi-phase DS-CDMA. Numerical examples by Monte Carlo simulation are presented to illustrate the GD Per performance for square-root raised-cosine pulses and spreading factors of moderate to large values. Also, a superiority of GD employment in CDMA systems over the Neyman-Pearson receiver is demonstrated

Multi-voxel pattern analysis reveals increased memory targeting and reduced use of retrieved details during single-agenda source monitoring

PubMed Central

McDuff, Susan G. R.; Frankel, Hillary C.; Norman, Kenneth A.

2009-01-01

We used multi-voxel pattern analysis (MVPA) of fMRI data to gain insight into how subjects’ retrieval agendas influence source memory judgments (was item X studied using source Y?). In Experiment 1, we used a single-agenda test where subjects judged whether items were studied with the targeted source or not. In Experiment 2, we used a multi-agenda test where subjects judged whether items were studied using the targeted source, studied using a different source, or nonstudied. To evaluate the differences between single- and multi-agenda source monitoring, we trained a classifier to detect source-specific fMRI activity at study, and then we applied the classifier to data from the test phase. We focused on trials where the targeted source and the actual source differed, so we could use MVPA to track neural activity associated with both the targeted source and the actual source. Our results indicate that single-agenda monitoring was associated with increased focus on the targeted source (as evidenced by increased targeted-source activity, relative to baseline) and reduced use of information relating to the actual, non-target source. In the multi-agenda experiment, high-levels of actual-source activity were associated with increased correct rejections, suggesting that subjects were using recollection of actual-source information to avoid source memory errors. In the single-agenda experiment, there were comparable levels of actual-source activity (suggesting that recollection was taking place), but the relationship between actual-source activity and behavior was absent (suggesting that subjects were failing to make proper use of this information). PMID:19144851

Optimized swimmer tracking system based on a novel multi-related-targets approach

NASA Astrophysics Data System (ADS)

Benarab, D.; Napoléon, T.; Alfalou, A.; Verney, A.; Hellard, P.

2017-02-01

Robust tracking is a crucial step in automatic swimmer evaluation from video sequences. We designed a robust swimmer tracking system using a new multi-related-targets approach. The main idea is to consider the swimmer as a bloc of connected subtargets that advance at the same speed. If one of the subtargets is partially or totally occluded, it can be localized by knowing the position of the others. In this paper, we first introduce the two-dimensional direct linear transformation technique that we used to calibrate the videos. Then, we present the classical tracking approach based on dynamic fusion. Next, we highlight the main contribution of our work, which is the multi-related-targets tracking approach. This approach, the classical head-only approach and the ground truth are then compared, through testing on a database of high-level swimmers in training, national and international competitions (French National Championships, Limoges 2015, and World Championships, Kazan 2015). Tracking percentage and the accuracy of the instantaneous speed are evaluated and the findings show that our new appraoach is significantly more accurate than the classical approach.

Measurement of the decay constant f(Ds+) using D(s+)-->l+ nu.

PubMed

Artuso, M; Blusk, S; Butt, J; Khalil, S; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Ecklund, K M; Severini, H; Love, W; Savinov, V; Aquines, O; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F

2007-08-17

We measure the decay constant f(Ds+) using the D(s+)-->l+ nu channel, where the l+ designates either a mu+ or a tau+, when the tau+ -->pi+ nu. Using both measurements we find f(Ds+)=274+/-13+/-7 MeV. Combining with our previous determination of f(D+), we compute the ratio f(Ds+)/f(D+)=1.23+/-0.11+/-0.04. We compare with theoretical estimates.

Titanium-Dioxide Nano-Fiber-Cotton Targets for Efficient Multi-keV X-Ray Generation

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

Tanabe, M; Nishimura, H; Fujioka, S

Multi-keV x-ray generation from low-density (27 {+-} 7 mg/cc) nano-fiber-cotton targets composed of titanium-dioxide has been investigated. The cotton targets were heated volumetrically and supersonically to a peak electron temperature of 2.3 keV, which is optimal to yield Ti K-shell x rays. Considerable enhancement of conversion efficiency (3.7 {+-} 0.5%) from incident laser energy into Ti K-shell x rays (4-6 keV band) was attained in comparison with that (1.4 {+-} 0.9%) for a planar Ti-foil target.

DS-Connect™: A Promising Tool to Improve Lives and Engage Down Syndrome Communities Worldwide

PubMed Central

Parisi, Melissa A.; Kaeser, Lisa; Bardhan, Sujata; Oster-Granite, MaryLou; Maddox, Yvonne T.

2015-01-01

Down syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities (IDDs) in the United States with an estimated birth prevalence of 1:691 births (http://www.cdc.gov/ncbddd/birthdefects/data.html); however, worldwide estimates of the number of individuals with IDDs, including DS, remain speculative. Little is known about the global health impact of DS, such as heart defects, gastrointestinal malformations, and other medical and behavioral issues. Further research is needed to develop the next generation of novel therapies and compounds aimed at improving cognition, reducing dementia and mitigating other manifestations of DS. To address these challenges, the National Institutes of Health (NIH) has created the first web-based, voluntary registry and data resource called DS-Connect™: The Down Syndrome Registry (https://DSConnect.nih.gov) to collect demographic and health information about individuals with DS. PMID:26271554

Neutron-rich isotope production using the uranium carbide multi-foil SPES target prototype

NASA Astrophysics Data System (ADS)

Scarpa, D.; Biasetto, L.; Corradetti, S.; Manzolaro, M.; Andrighetto, A.; Carturan, S.; Prete, G.; Zanonato, P.; Stracener, D. W.

2011-03-01

In the framework of the R&D program for the SPES (Selective Production of Exotic Species) project of the Istituto Nazionale di Fisica Nucleare (INFN), production yields of neutron-rich isotopes have been measured at the Holifield Radioactive Ion Beam Facility (HRIBF, Oak Ridge National Laboratory, USA). This experiment makes use of the multi-foil SPES target prototype composed of 7 uranium carbide discs, with excess of graphite (ratio C/ U = 4 . 77 isotopes of medium mass (between 72 and 141amu), produced via proton-induced fission of uranium using a 40MeV proton beam, have been collected and analyzed for the target heated at 2000 ° C target temperature.

dsRNA binding properties of RDE-4 and TRBP reflect their distinct roles in RNAi.

PubMed

Parker, Greg S; Maity, Tuhin Subhra; Bass, Brenda L

2008-12-26

Double-stranded RNA (dsRNA)-binding proteins facilitate Dicer functions in RNA interference. Caenorhabditis elegans RDE-4 facilitates cleavage of long dsRNA to small interfering RNA (siRNA), while human trans-activation response RNA-binding protein (TRBP) functions downstream to pass siRNA to the RNA-induced silencing complex. We show that these distinct in vivo roles are reflected in in vitro binding properties. RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. These properties are mechanistically based on the fact that RDE-4 binds cooperatively, via contributions from multiple domains, while TRBP binds noncooperatively. Our studies offer a paradigm for how dsRNA-binding proteins, which are not sequence specific, discern dsRNA length. Additionally, analyses of the ability of RDE-4 deletion constructs and RDE-4/TRBP chimeras to reconstitute Dicer activity suggest RDE-4 promotes activity using its dsRNA-binding motif 2 to bind dsRNA, its linker region to interact with Dicer, and its C-terminus for Dicer activation.

Improving performance of DS-CDMA systems using chaotic complex Bernoulli spreading codes

NASA Astrophysics Data System (ADS)

Farzan Sabahi, Mohammad; Dehghanfard, Ali

2014-12-01

The most important goal of spreading spectrum communication system is to protect communication signals against interference and exploitation of information by unintended listeners. In fact, low probability of detection and low probability of intercept are two important parameters to increase the performance of the system. In Direct Sequence Code Division Multiple Access (DS-CDMA) systems, these properties are achieved by multiplying the data information in spreading sequences. Chaotic sequences, with their particular properties, have numerous applications in constructing spreading codes. Using one-dimensional Bernoulli chaotic sequence as spreading code is proposed in literature previously. The main feature of this sequence is its negative auto-correlation at lag of 1, which with proper design, leads to increase in efficiency of the communication system based on these codes. On the other hand, employing the complex chaotic sequences as spreading sequence also has been discussed in several papers. In this paper, use of two-dimensional Bernoulli chaotic sequences is proposed as spreading codes. The performance of a multi-user synchronous and asynchronous DS-CDMA system will be evaluated by applying these sequences under Additive White Gaussian Noise (AWGN) and fading channel. Simulation results indicate improvement of the performance in comparison with conventional spreading codes like Gold codes as well as similar complex chaotic spreading sequences. Similar to one-dimensional Bernoulli chaotic sequences, the proposed sequences also have negative auto-correlation. Besides, construction of complex sequences with lower average cross-correlation is possible with the proposed method.

Cryo-EM near-atomic structure of a dsRNA fungal virus shows ancient structural motifs preserved in the dsRNA viral lineage

PubMed Central

Luque, Daniel; Gómez-Blanco, Josué; Garriga, Damiá; Brilot, Axel F.; González, José M.; Havens, Wendy M.; Carrascosa, José L.; Trus, Benes L.; Verdaguer, Nuria; Ghabrial, Said A.; Castón, José R.

2014-01-01

Viruses evolve so rapidly that sequence-based comparison is not suitable for detecting relatedness among distant viruses. Structure-based comparisons suggest that evolution led to a small number of viral classes or lineages that can be grouped by capsid protein (CP) folds. Here, we report that the CP structure of the fungal dsRNA Penicillium chrysogenum virus (PcV) shows the progenitor fold of the dsRNA virus lineage and suggests a relationship between lineages. Cryo-EM structure at near-atomic resolution showed that the 982-aa PcV CP is formed by a repeated α-helical core, indicative of gene duplication despite lack of sequence similarity between the two halves. Superimposition of secondary structure elements identified a single “hotspot” at which variation is introduced by insertion of peptide segments. Structural comparison of PcV and other distantly related dsRNA viruses detected preferential insertion sites at which the complexity of the conserved α-helical core, made up of ancestral structural motifs that have acted as a skeleton, might have increased, leading to evolution of the highly varied current structures. Analyses of structural motifs only apparent after systematic structural comparisons indicated that the hallmark fold preserved in the dsRNA virus lineage shares a long (spinal) α-helix tangential to the capsid surface with the head-tailed phage and herpesvirus viral lineage. PMID:24821769

Targeting community-dwelling urinary incontinence sufferers: a multi-disciplinary community based model for conservative continence services.

PubMed

St John, Winsome; Wallis, Marianne; James, Heather; McKenzie, Shona; Guyatt, Sheridan

2004-10-01

This paper presents an argument that there is a need to provide services that target community-dwelling incontinence sufferers, and presents a demonstration case study of a multi-disciplinary, community-based conservative model of service delivery: The Waterworx Model. Rationale for approaches taken, implementation of the model, evaluation and lessons learned are discussed. In this paper community-dwelling sufferers of urinary incontinence are identified as an underserved group, and useful information is provided for those wishing to establish services for them. The Waterworx Model of continence service delivery incorporates three interrelated approaches. Firstly, client access is achieved by using community-based services via clinic and home visits, creating referral pathways and active promotion of services. Secondly, multi-disciplinary client care is provided by targeting a specific client group, multi-disciplinary assessment, promoting client self-management and developing client knowledge and health literacy. Finally, interdisciplinary collaboration and linkages is facilitated by developing multidisciplinary assessment tools, using interdisciplinary referrals, staff development, multi-disciplinary management and providing professional education. Implementation of the model achieved greater client access, improvement in urinary incontinence and client satisfaction. Our experiences suggest that those suffering urinary incontinence and living in the community are an underserved group and that continence services should be community focussed, multi-disciplinary, generalist in nature.

Application of Advanced Multi-Core Processor Technologies to Oceanographic Research

DTIC Science & Technology

2013-09-30

STM32 NXP LPC series No Proprietary Microchip PIC32/DSPIC No > 500 mW; < 5 W ARM Cortex TI OMAP TI Sitara Broadcom BCM2835 Varies FPGA...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Application of Advanced Multi-Core Processor Technologies...state-of-the-art information processing architectures. OBJECTIVES Next-generation processor architectures (multi-core, multi-threaded) hold the

Multi-Target Tracking Using an Improved Gaussian Mixture CPHD Filter.

PubMed

Si, Weijian; Wang, Liwei; Qu, Zhiyu

2016-11-23

The cardinalized probability hypothesis density (CPHD) filter is an alternative approximation to the full multi-target Bayesian filter for tracking multiple targets. However, although the joint propagation of the posterior intensity and cardinality distribution in its recursion allows more reliable estimates of the target number than the PHD filter, the CPHD filter suffers from the spooky effect where there exists arbitrary PHD mass shifting in the presence of missed detections. To address this issue in the Gaussian mixture (GM) implementation of the CPHD filter, this paper presents an improved GM-CPHD filter, which incorporates a weight redistribution scheme into the filtering process to modify the updated weights of the Gaussian components when missed detections occur. In addition, an efficient gating strategy that can adaptively adjust the gate sizes according to the number of missed detections of each Gaussian component is also presented to further improve the computational efficiency of the proposed filter. Simulation results demonstrate that the proposed method offers favorable performance in terms of both estimation accuracy and robustness to clutter and detection uncertainty over the existing methods.

Coded DS-CDMA Systems with Iterative Channel Estimation and no Pilot Symbols

DTIC Science & Technology

2010-08-01

ar X iv :1 00 8. 31 96 v1 [ cs .I T ] 1 9 A ug 2 01 0 1 Coded DS - CDMA Systems with Iterative Channel Estimation and no Pilot Symbols Don...sequence code-division multiple-access ( DS - CDMA ) systems with quadriphase-shift keying in which channel estimation, coherent demodulation, and decoding...amplitude, phase, and the interference power spectral density (PSD) due to the combined interference and thermal noise is proposed for DS - CDMA systems

Four-dimensional characterization of inflow to and wakes from a multi-MW turbine: overview of the Turbine Wake and Inflow Characterization Study (TWICS2011)

NASA Astrophysics Data System (ADS)

Lundquist, J. K.; Banta, R. M.; Pichugina, Y.; Brewer, A.; Alvarez, R. J.; Sandberg, S. P.; Kelley, N. D.; Aitken, M.; Clifton, A.; Mirocha, J. D.

2011-12-01

To support substantial deployment of renewably-generated electricity from the wind, critical information about the variability of wind turbine wakes in the real atmosphere from multi-MW turbines is required. The assessment of the velocity deficit and turbulence associated with industrial-scale turbines is a major issue for wind farm design, particularly with respect to the optimization of the spacing between turbines. The significant velocity deficit and turbulence generated by upstream turbines can reduce the power production and produce harmful vibrations in downstream turbines, which can lead to excess maintenance costs. The complexity of wake effects depends on many factors arising from both hardware (turbine size, rotor speed, and blade geometry, etc.) and from meteorological considerations such as wind velocity, gradients of wind across the turbine rotor disk, atmospheric stability, and atmospheric turbulence. To characterize the relationships between the meteorological inflow and turbine wakes, a collaborative field campaign was designed and carried out at the Department of Energy's National Wind Technology Center (NREL/NWTC) in south Boulder, Colorado, in spring 2011. This site often experiences channeled flow with a consistent wind direction, enabling robust statistics of wake velocity deficits and turbulence enhancements. Using both in situ and remote sensing instrumentation, measurements upwind and downwind of multi-megawatt wind turbine in complex terrain quantified the variability of wind turbine inflow and wakes from an industrial-scale turbine. The turbine of interest has a rated power of 2.3 MW, a rotor diameter of 100m, and a hub height of 80m. In addition to several meteorological towers, one extending to hub height (80m) and another extending above the top of the rotor disk (135m), a Triton mini-sodar and a Windcube lidar characterized the inflow to the turbine and the variability across the site. The centerpiece instrument of the TWICS campaign

The role of attitudes towards the targets of behaviour in predicting and informing prenatal testing choices.

PubMed

Bryant, Louise D; Green, Josephine M; Hewison, Jenny

2010-12-01

Research considering the role of attitudes in prenatal testing choices has commonly focused on the relationship between the attitude towards undergoing testing and actual testing behaviour. In contrast, this study focused on the relationship between testing behaviour and attitudes towards the targets of the behaviour (in this case people with Down syndrome (DS) and having a baby with DS). A cross-sectional, prospective survey of 197 pregnant women measured attitudes towards the targets of prenatal testing along with intentions to use screening and diagnostic testing, and the termination of an affected pregnancy. Screening uptake was established via patient records. Although attitudes towards DS and having a baby with DS were significantly associated with screening uptake and testing and termination intentions, unfavourable attitudes were better than favourable ones at predicting these outcomes. For example, in the quartile of women with the 'most favourable' attitude towards people with DS 67% used screening although only 8% said they would terminate an affected pregnancy. Qualitative data suggested that not all women considered personal attitudes towards DS to be relevant to their screening decisions. This finding has implications for the way in which informed choice is currently understood and measured in the prenatal testing context.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed

Straube, Andreas; Aicher, Bernhard; Fiebich, Bernd L; Haag, Gunther

2011-03-31

Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect.As an example the fixed-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic

ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy.

PubMed

Marco-Contelles, José; Unzeta, Mercedes; Bolea, Irene; Esteban, Gerard; Ramsay, Rona R; Romero, Alejandro; Martínez-Murillo, Ricard; Carreiras, M Carmo; Ismaili, Lhassane

2016-01-01

ASS2324 is a hybrid compound resulting from the juxtaposition of donepezil and the propargylamine PF9601N ASS2324 is a multi-target directed propargylamine able to bind to all the AChE/BuChE and MAO A/B enzymesASS2324 shows antioxidant, neuroprotective and suitable permeability propertiesASS2324 restores the scopolamine-induced cognitive impairment to the same extent as donepezil, and is less toxicASS2324 prevents β-amyloid induced aggregation in the cortex of double transgenic miceASS2324 is the most advanced anti-Alzheimer agent for pre-clinical studies that we have identified in our laboratories The complex nature of Alzheimer's disease (AD) has prompted the design of Multi-Target-Directed Ligands (MTDL) able to bind to diverse biochemical targets involved in the progress and development of the disease. In this context, we have designed a number of MTD propargylamines (MTDP) showing antioxidant, anti-beta-amyloid, anti-inflammatory, as well as cholinesterase and monoamine oxidase (MAO) inhibition capacities. Here, we describe these properties in the MTDL ASS234, our lead-compound ready to enter in pre-clinical studies for AD, as a new multipotent, permeable cholinesterase/monoamine oxidase inhibitor, able to inhibit Aβ-aggregation, and possessing antioxidant and neuroprotective properties.

A network-based multi-target computational estimation scheme for anticoagulant activities of compounds.

PubMed

Li, Qian; Li, Xudong; Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-03-22

Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. This article proposes a network-based multi-target computational estimation method for anticoagulant activities of compounds by

A Network-Based Multi-Target Computational Estimation Scheme for Anticoagulant Activities of Compounds

PubMed Central

Li, Canghai; Chen, Lirong; Song, Jun; Tang, Yalin; Xu, Xiaojie

2011-01-01

Background Traditional virtual screening method pays more attention on predicted binding affinity between drug molecule and target related to a certain disease instead of phenotypic data of drug molecule against disease system, as is often less effective on discovery of the drug which is used to treat many types of complex diseases. Virtual screening against a complex disease by general network estimation has become feasible with the development of network biology and system biology. More effective methods of computational estimation for the whole efficacy of a compound in a complex disease system are needed, given the distinct weightiness of the different target in a biological process and the standpoint that partial inhibition of several targets can be more efficient than the complete inhibition of a single target. Methodology We developed a novel approach by integrating the affinity predictions from multi-target docking studies with biological network efficiency analysis to estimate the anticoagulant activities of compounds. From results of network efficiency calculation for human clotting cascade, factor Xa and thrombin were identified as the two most fragile enzymes, while the catalytic reaction mediated by complex IXa:VIIIa and the formation of the complex VIIIa:IXa were recognized as the two most fragile biological matter in the human clotting cascade system. Furthermore, the method which combined network efficiency with molecular docking scores was applied to estimate the anticoagulant activities of a serial of argatroban intermediates and eight natural products respectively. The better correlation (r = 0.671) between the experimental data and the decrease of the network deficiency suggests that the approach could be a promising computational systems biology tool to aid identification of anticoagulant activities of compounds in drug discovery. Conclusions This article proposes a network-based multi-target computational estimation method for

[22q11.2DS Syndrome as a Genetic Subtype of Schizophrenia].

PubMed

Huertas-Rodríguez, Cindy Katherin; Payán-Gómez, César; Forero-Castro, Ruth Maribel

2015-01-01

The 22q11.2 deletion syndrome (22q11.2DS) is associated with the microdeletion of this chromosomal region, and represents the second most common genetic syndrome after Down's syndrome. In patients with schizophrenia, 22q11.2DS has a prevalence of 2%, and in selected groups can be increased to between 32-53%. To describe the generalities of 22q11.2DS syndrome as a genetic subtype of schizophrenia, its clinical characteristics, molecular genetic aspects, and frequency in different populations. A review was performed from 1967 to 2013 in scientific databases, compiling articles about 22q11.2DS syndrome and its association with schizophrenia. The 22q11.2 DS syndrome has a variable phenotype associated with other genetic syndromes, birth defects in many tissues and organs, and a high rate of psychiatric disorders, particularly schizophrenia. Likewise, it has been identified in clinical populations with schizophrenia selected by the presence of common syndromic characteristics. FISH, qPCR and MLPA techniques, and recently, aCGH and NGS technologies, are being used to diagnose this microdeletion. It is important in clinical practice to remember that people suffering the 22q11.2DS have a high genetic risk for developing schizophrenia, and it is considered that the simultaneous presence of this disease and 22q11.2DS represents a genetic subtype of schizophrenia. There are clear phenotypic criteria, molecular and cytogenetic methods to diagnose this group of patients, and to optimize a multidisciplinary approach in their monitoring. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

PubMed

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority <15.4%) of the individual target inhibitors of the same target pair and 0.58-7.1% of the other 6 targets outside the target pair. COMBI-SVMs showed low dual inhibitor false hit rates (0.006-0.056%, 0.042-0.21%, 0.2-4%) in screening 17 million PubChem compounds, 168,000 MDDR compounds, and 7-8181 MDDR compounds similar to the dual inhibitors. Compared with similarity searching, k-NN and PNN methods, COMBI-SVM produced comparable dual inhibitor yields, similar target selectivity, and lower false hit rate in screening 168,000 MDDR compounds. The annotated classes of many COMBI-SVMs identified MDDR virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Novel anti-EPHA2 antibody, DS-8895a for cancer treatment.

PubMed

Hasegawa, Jun; Sue, Mayumi; Yamato, Michiko; Ichikawa, Junya; Ishida, Saori; Shibutani, Tomoko; Kitamura, Michiko; Wada, Teiji; Agatsuma, Toshinori

2016-11-01

Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models. Moreover, DS-8895a in combination with cisplatin (CDDP) showed better efficacy than each of the monotherapies did in the human gastric cancer model. These results suggest that a novel antibody, DS-8895a has therapeutic potential against EPHA2-expressing tumors.

Novel anti-EPHA2 antibody, DS-8895a for cancer treatment

PubMed Central

Hasegawa, Jun; Sue, Mayumi; Yamato, Michiko; Ichikawa, Junya; Ishida, Saori; Shibutani, Tomoko; Kitamura, Michiko; Wada, Teiji; Agatsuma, Toshinori

2016-01-01

ABSTRACT Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models. Moreover, DS-8895a in combination with cisplatin (CDDP) showed better efficacy than each of the monotherapies did in the human gastric cancer model. These results suggest that a novel antibody, DS-8895a has therapeutic potential against EPHA2-expressing tumors. PMID:27653549

Data association approaches in bearings-only multi-target tracking

NASA Astrophysics Data System (ADS)

Xu, Benlian; Wang, Zhiquan

2008-03-01

According to requirements of time computation complexity and correctness of data association of the multi-target tracking, two algorithms are suggested in this paper. The proposed Algorithm 1 is developed from the modified version of dual Simplex method, and it has the advantage of direct and explicit form of the optimal solution. The Algorithm 2 is based on the idea of Algorithm 1 and rotational sort method, it combines not only advantages of Algorithm 1, but also reduces the computational burden, whose complexity is only 1/ N times that of Algorithm 1. Finally, numerical analyses are carried out to evaluate the performance of the two data association algorithms.

Dispersion of bamboo type multi-wall carbon nanotubes in calf-thymus double stranded DNA.

PubMed

Primo, Emiliano N; Cañete-Rosales, Paulina; Bollo, Soledad; Rubianes, María D; Rivas, Gustavo A

2013-08-01

We report for the first time the use of double stranded calf-thymus DNA (dsDNA) to successfully disperse bamboo-like multi-walled carbon nanotubes (bCNT). The dispersion and the modified electrodes were studied by different spectroscopic, microscopic and electrochemical techniques. The drastic treatment for dispersing the bCNT (45min sonication in a 50% (v/v) ethanol:water solution), produces a partial denaturation and a decrease in the length of dsDNA that facilitates the dispersion of CNT and makes possible an efficient electron transfer of guanine residues to the electrode. A critical analysis of the influence of different experimental conditions on the efficiency of the dispersion and on the performance of glassy carbon electrodes (GCE) modified with bCNT-dsDNA dispersion is also reported. The electron transfer of redox probes and guanine residues was more efficient at GCE modified with bCNT dispersed in dsDNA than at GCE modified with hollow CNT (hCNT) dispersed in dsDNA, demonstrating the importance of the presence of bCNT. Copyright © 2013 Elsevier B.V. All rights reserved.

The influenza virus NS1 protein as a therapeutic target.

PubMed

Engel, Daniel A

2013-09-01

Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2'-5' oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN-β mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

The influenza virus NS1 protein as a therapeutic target

PubMed Central

Engel, Daniel A.

2015-01-01

Nonstructural protein 1 (NS1) of influenza A virus plays a central role in virus replication and blockade of the host innate immune response, and is therefore being considered as a potential therapeutic target. The primary function of NS1 is to dampen the host interferon (IFN) response through several distinct molecular mechanisms that are triggered by interactions with dsRNA or specific cellular proteins. Sequestration of dsRNA by NS1 results in inhibition of the 2’-5’ oligoadenylate synthetase/RNase L antiviral pathway, and also inhibition of dsRNA-dependent signaling required for new IFN production. Binding of NS1 to the E3 ubiquitin ligase TRIM25 prevents activation of RIG-I signaling and subsequent IFN induction. Cellular RNA processing is also targeted by NS1, through recognition of cleavage and polyadenylation specificity factor 30 (CPSF30), leading to inhibition of IFN- mRNA processing as well as that of other cellular mRNAs. In addition NS1 binds to and inhibits cellular protein kinase R (PKR), thus blocking an important arm of the IFN system. Many additional proteins have been reported to interact with NS1, either directly or indirectly, which may serve its anti-IFN and additional functions, including the regulation of viral and host gene expression, signaling pathways and viral pathogenesis. Many of these interactions are potential targets for small-molecule intervention. Structural, biochemical and functional studies have resulted in hypotheses for drug discovery approaches that are beginning to bear experimental fruit, such as targeting the dsRNA-NS1 interaction, which could lead to restoration of innate immune function and inhibition of virus replication. This review describes biochemical, cell-based and nucleic acid-based approaches to identifying NS1 antagonists. PMID:23796981

Exploring the molecular basis of dsRNA recognition by NS1 protein of influenza A virus using molecular dynamics simulation and free energy calculation.

PubMed

Pan, Dabo; Sun, Huijun; Shen, Yulin; Liu, Huanxiang; Yao, Xiaojun

2011-12-01

The frequent outbreak of influenza pandemic and the limited available anti-influenza drugs highlight the urgent need for the development of new antiviral drugs. The dsRNA-binding surface of nonstructural protein 1 of influenza A virus (NS1A) is a promising target. The detailed understanding of NS1A-dsRNA interaction will be valuable for structure-based anti-influenza drug discovery. To characterize and explore the key interaction features between dsRNA and NS1A, molecular dynamics simulation combined with MM-GBSA calculations were performed. Based on the MM-GBSA calculations, we find that the intermolecular van der Waals interaction and the nonpolar solvation term provide the main driving force for the binding process. Meanwhile, 17 key residues from NS1A were identified to be responsible for the dsRNA binding. Compared with the wild type NS1A, all the studied mutants S42A, T49A, R38A, R35AR46A have obvious reduced binding free energies with dsRNA reflecting in the reduction of the polar and/or nonpolar interactions. In addition, the structural and energy analysis indicate the mutations have a small effect to the backbone structures but the loss of side chain interactions is responsible for the decrease of the binding affinity. The uncovering of NS1A-dsRNA recognition mechanism will provide some useful insights and new chances for the development of anti-influenza drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

A set of GFP-based organelle marker lines combined with DsRed-based gateway vectors for subcellular localization study in rice (Oryza sativa L.).

PubMed

Wu, Tsung-Meng; Lin, Ke-Chun; Liau, Wei-Shiang; Chao, Yun-Yang; Yang, Ling-Hung; Chen, Szu-Yun; Lu, Chung-An; Hong, Chwan-Yang

2016-01-01

In the post-genomic era, many useful tools have been developed to accelerate the investigation of gene functions. Fluorescent proteins have been widely used as protein tags for studying the subcellular localization of proteins in plants. Several fluorescent organelle marker lines have been generated in dicot plants; however, useful and reliable fluorescent organelle marker lines are lacking in the monocot model rice. Here, we developed eight different GFP-based organelle markers in transgenic rice and created a set of DsRed-based gateway vectors for combining with the marker lines. Two mitochondrial-localized rice ascorbate peroxidase genes fused to DsRed and successfully co-localized with mitochondrial-targeted marker lines verified the practical use of this system. The co-localization of GFP-fusion marker lines and DsRed-fusion proteins provide a convenient platform for in vivo or in vitro analysis of subcellular localization of rice proteins.

Iterative Overlap FDE for Multicode DS-CDMA

NASA Astrophysics Data System (ADS)

Takeda, Kazuaki; Tomeba, Hiromichi; Adachi, Fumiyuki

Recently, a new frequency-domain equalization (FDE) technique, called overlap FDE, that requires no GI insertion was proposed. However, the residual inter/intra-block interference (IBI) cannot completely be removed. In addition to this, for multicode direct sequence code division multiple access (DS-CDMA), the presence of residual interchip interference (ICI) after FDE distorts orthogonality among the spreading codes. In this paper, we propose an iterative overlap FDE for multicode DS-CDMA to suppress both the residual IBI and the residual ICI. In the iterative overlap FDE, joint minimum mean square error (MMSE)-FDE and ICI cancellation is repeated a sufficient number of times. The bit error rate (BER) performance with the iterative overlap FDE is evaluated by computer simulation.

A target development program for beamhole spallation neutron sources in the megawatt range

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

Bauer, G.S.; Atchison, F.

1995-10-01

Spallation sources as an alternative to fission neutron sources have been operating successfully up to 160 kW of beam power. With the next generation of these facilities aiming at the medium power range between 0.5 and 5 MW, loads on the targets will be high enough to make present experience of little relevance. With the 0.6 MW continuous facility SINQ under construction, and a 5 MW pulsed facility (ESS) under study in Europe, a research and development program is about to be started which aimes at assessing the limits of stationary and moving solid targets and the feasibility and potentialmore » benefits of flowing liquid metal targets. Apart from theoretical work and examination of existing irradiated material, including used targets from ISIS, it is intended to take advantage of the SINQ solid rod target design to improve the relevant data base by building the target in such a way that individual rods can be equipped as irradiation capsules.« less

DS-CDMA satellite diversity reception for personal satellite communication: Downlink performance analysis

NASA Technical Reports Server (NTRS)

DeGaudenzi, Riccardo; Giannetti, Filippo

1995-01-01

The downlink of a satellite-mobile personal communication system employing power-controlled Direct Sequence Code Division Multiple Access (DS-CDMA) and exploiting satellite-diversity is analyzed and its performance compared with a more traditional communication system utilizing single satellite reception. The analytical model developed has been thoroughly validated by means of extensive Monte Carlo computer simulations. It is shown how the capacity gain provided by diversity reception shrinks considerably in the presence of increasing traffic or in the case of light shadowing conditions. Moreover, the quantitative results tend to indicate that to combat system capacity reduction due to intra-system interference, no more than two satellites shall be active over the same region. To achieve higher system capacity, differently from terrestrial cellular systems, Multi-User Detection (MUD) techniques are likely to be required in the mobile user terminal, thus considerably increasing its complexity.

Creating opportunities for science PhDs to pursue careers in high school education

PubMed Central

Doyle, Kari M. H.; Vale, Ronald D.

2013-01-01

The United States is confronting important challenges at both the early and late stages of science education. At the level of K–12 education, a recent National Research Council report (Successful K–12 STEM Education) proposed a bold restructuring of how science is taught, moving away from memorizing facts and emphasizing hands-on, inquiry-based learning and a deeper understanding of the process of science. At higher levels of training, limited funding for science is leading PhDs to seek training and careers in areas other than research. Might science PhDs play a bigger role in the future of K–12 education, particularly at the high school level? We explore this question by discussing the roles that PhDs can play in high school education and the current and rather extensive barriers to PhDs entering the teaching profession and finally suggest ways to ease the entrance of qualified PhDs into high school education. PMID:24174464

Creating opportunities for science PhDs to pursue careers in high school education.

PubMed

Doyle, Kari M H; Vale, Ronald D

2013-11-01

The United States is confronting important challenges at both the early and late stages of science education. At the level of K-12 education, a recent National Research Council report (Successful K-12 STEM Education) proposed a bold restructuring of how science is taught, moving away from memorizing facts and emphasizing hands-on, inquiry-based learning and a deeper understanding of the process of science. At higher levels of training, limited funding for science is leading PhDs to seek training and careers in areas other than research. Might science PhDs play a bigger role in the future of K-12 education, particularly at the high school level? We explore this question by discussing the roles that PhDs can play in high school education and the current and rather extensive barriers to PhDs entering the teaching profession and finally suggest ways to ease the entrance of qualified PhDs into high school education.

One-Compound-Multi-Target: Combination Prospect of Natural Compounds with Thrombolytic Therapy in Acute Ischemic Stroke

PubMed Central

Chen, Han-Sen; Qi, Su-Hua; Shen, Jian-Gang

2017-01-01

Abstract: Tissue plasminogen activator (t-PA) is the only FDA-approved drug for acute ischemic stroke treatment, but its clinical use is limited due to the narrow therapeutic time window and severe adverse effects, including hemorrhagic transformation (HT) and neurotoxicity. One of the potential resolutions is to use adjunct therapies to reduce the side effects and extend t-PA's therapeutic time window. However, therapies modulating single target seem not to be satisfied, and a multi-target strategy is warranted to resolve such complex disease. Recently, large amount of efforts have been made to explore the active compounds from herbal supplements to treat ischemic stroke. Some natural compounds revealed both neuro- and blood-brain-barrier (BBB)-protective effects by concurrently targeting multiple cellular signaling pathways in cerebral ischemia-reperfusion injury. Thus, those compounds are potential to be one-drug-multi-target agents as combined therapy with t-PA for ischemic stroke. In this review article, we summarize current progress about molecular targets involving in t-PA-mediated HT and neurotoxicity in ischemic brain injury. Based on these targets, we select 23 promising compounds from currently available literature with the bioactivities simultaneously targeting several important molecular targets. We propose that those compounds merit further investigation as combined therapy with t-PA. Finally, we discuss the potential drawbacks of the natural compounds' studies and raise several important issues to be addressed in the future for the development of natural compound as an adjunct therapy. PMID:27334020

Maternal uterine NK cell–activating receptor KIR2DS1 enhances placentation

PubMed Central

Xiong, Shiqiu; Sharkey, Andrew M.; Kennedy, Philippa R.; Gardner, Lucy; Farrell, Lydia E.; Chazara, Olympe; Bauer, Julien; Hiby, Susan E.; Colucci, Francesco; Moffett, Ashley

2013-01-01

Reduced trophoblast invasion and vascular conversion in decidua are thought to be the primary defect of common pregnancy disorders including preeclampsia and fetal growth restriction. Genetic studies suggest these conditions are linked to combinations of polymorphic killer cell Ig-like receptor (KIR) genes expressed by maternal decidual NK cells (dNK) and HLA-C genes expressed by fetal trophoblast. Inhibitory KIR2DL1 and activating KIR2DS1 both bind HLA-C2, but confer increased risk or protection from pregnancy disorders, respectively. The mechanisms underlying these genetic associations with opposing outcomes are unknown. We show that KIR2DS1 is highly expressed in dNK, stimulating strong activation of KIR2DS1+ dNK. We used microarrays to identify additional responses triggered by binding of KIR2DS1 or KIR2DL1 to HLA-C2 and found different responses in dNK coexpressing KIR2DS1 with KIR2DL1 compared with dNK only expressing KIR2DL1. Activation of KIR2DS1+ dNK by HLA-C2 stimulated production of soluble products including GM-CSF, detected by intracellular FACS and ELISA. We demonstrated that GM-CSF enhanced migration of primary trophoblast and JEG-3 trophoblast cells in vitro. These findings provide a molecular mechanism explaining how recognition of HLA class I molecules on fetal trophoblast by an activating KIR on maternal dNK may be beneficial for placentation. PMID:24091323

A performance analysis of DS-CDMA and SCPC VSAT networks

NASA Technical Reports Server (NTRS)

Hayes, David P.; Ha, Tri T.

1990-01-01

Spread-spectrum and single-channel-per-carrier (SCPC) transmission techniques work well in very small aperture terminal (VSAT) networks for multiple-access purposes while allowing the earth station antennas to remain small. Direct-sequence code-division multiple-access (DS-CDMA) is the simplest spread-spectrum technique to use in a VSAT network since a frequency synthesizer is not required for each terminal. An examination is made of the DS-CDMA and SCPC Ku-band VSAT satellite systems for low-density (64-kb/s or less) communications. A method for improving the standardf link analysis of DS-CDMA satellite-switched networks by including certain losses is developed. The performance of 50-channel full mesh and star network architectures is analyzed. The selection of operating conditions producing optimum performance is demonstrated.

Thermally driven spin-Seebeck transport in chiral dsDNA-based molecular devices

NASA Astrophysics Data System (ADS)

Nian, L. L.; Zhang, Rong; Tang, F. R.; Tang, Jun; Bai, Long

2018-03-01

By employing the nonequilibrium Green's function technique, we study the thermal-induced spin-Seebeck transport through a chiral double-stranded DNA (dsDNA) connected to a normal-metal and a ferromagnetic lead. How the main parameters of the dsDNA-based system influence the spin-Seebeck transport is analyzed at length, and the thermally created charge (spin-related) current displays the rectification effect and the negative differential thermal conductance feature. More importantly, the spin current exhibits the rectification behavior of the spin-Seebeck effect; even the perfect spin-Seebeck effect can be obtained with the null charge current. Thus, the chiral dsDNA-based system can act as a spin(charge)-Seebeck diode, spin(charge)-Seebeck switch, and spin(charge)-Seebeck transistor. Our results provide new ways to design spin caloritronic devices based on dsDNA or other organic molecules.

Ultra Clean 1.1MW High Efficiency Natural Gas Engine Powered System

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

Zurlo, James; Lueck, Steve

Dresser, Inc. (GE Energy, Waukesha gas engines) will develop, test, demonstrate, and commercialize a 1.1 Megawatt (MW) natural gas fueled combined heat and power reciprocating engine powered package. This package will feature a total efficiency > 75% and ultra low CARB permitting emissions. Our modular design will cover the 1 – 6 MW size range, and this scalable technology can be used in both smaller and larger engine powered CHP packages. To further advance one of the key advantages of reciprocating engines, the engine, generator and CHP package will be optimized for low initial and operating costs. Dresser, Inc. willmore » leverage the knowledge gained in the DOE - ARES program. Dresser, Inc. will work with commercial, regulatory, and government entities to help break down barriers to wider deployment of CHP. The outcome of this project will be a commercially successful 1.1 MW CHP package with high electrical and total efficiency that will significantly reduce emissions compared to the current central power plant paradigm. Principal objectives by phases for Budget Period 1 include: • Phase 1 – market study to determine optimum system performance, target first cost, lifecycle cost, and creation of a detailed product specification. • Phase 2 – Refinement of the Waukesha CHP system design concepts, identification of critical characteristics, initial evaluation of technical solutions, and risk mitigation plans. Background« less

Transmit/receive 3-20 GHz 1.2 mW packaged double-pole-16-throw switching matrix for radar-based target detection

NASA Astrophysics Data System (ADS)

Azhari, Afreen; Kuwano, Yuki; Xiao, Xia; Kikkawa, Takamaro

2018-01-01

A 3-20 GHz transmit/receive (T/R) double-pole-16-throw (DP16T) switching matrix has been developed on a printed circuit board (PCB) to control sixteen antennas in a radar-based portable breast-cancer detection system. The DP16T switch consists of four 65 nm CMOS 0.01-20 GHz double-pole-four-throw (DP4T) switches. The proposed switch increase the number of T/R combinations to 224 from the 196 of a conventional switching matrix in order to construct high-resolution images. Using this switch and a 4 × 4 slot antenna array, a 10 × 10 mm2 aluminum target was detected with an 8-GHz-center-frequency Gaussian monocycle pulse. The power consumption of the switch is only 1.2 mW. To the best of the authors’ knowledge, this is the first T/R radio frequency (RF) DP16T switching matrix, which was realized with four CMOS DP4T switches on a PCB and was measured with RF PCB connectors.

UKRAINIAN MULTI-FUEL REBURN DEMO

EPA Science Inventory

This research demonstrates a multi-fuel reburning system to allow the use of natural gas, fuel oil, or pulverized coal as the reburn fuel on a 300 MW wall-fired, we-bottom boiler in the Ukraine. The ability to use more than one fuel is critical to the success of reburning as a N...

Accumulation of dsRNA in endosomes contributes to inefficient RNA interference in the fall armyworm, Spodoptera frugiperda.

PubMed

Yoon, June-Sun; Gurusamy, Dhandapani; Palli, Subba Reddy

2017-11-01

RNA interference (RNAi) efficiency varies among insects studied. The barriers for successful RNAi include the presence of double-stranded ribonucleases (dsRNase) in the lumen and hemolymph that could potentially digest double-stranded RNA (dsRNA) and the variability in the transport of dsRNA into and within the cells. We recently showed that the dsRNAs are transported into lepidopteran cells, but they are not processed into small interference RNAs (siRNAs) because they are trapped in acidic bodies. In the current study, we focused on the identification of acidic bodies in which dsRNAs accumulate in Sf9 cells. Time-lapse imaging studies showed that dsRNAs enter Sf9 cells and accumulate in acidic bodies within 20 min after their addition to the medium. CypHer-5E-labeled dsRNA also accumulated in the midgut and fat body dissected from Spodoptera frugiperda larvae with similar patterns observed in Sf9 cells. Pharmacological inhibitor assays showed that the dsRNAs use clathrin mediated endocytosis pathway for transport into the cells. We investigated the potential dsRNA accumulation sites employing LysoTracker and double labeling experiments using the constructs to express a fusion of green fluorescence protein with early or late endosomal marker proteins and CypHer-5E-labeled dsRNA. Interestingly, CypHer-5E-labeled dsRNA accumulated predominantly in early and late endosomes. These data suggest that entrapment of internalized dsRNA in endosomes is one of the major factors contributing to inefficient RNAi response in lepidopteran insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Yawing characteristics during slippage of the nacelle of a multi MW wind turbine

NASA Astrophysics Data System (ADS)

Kim, M.-G.; Dalhoff, P. H.; Gust, P.

2016-09-01

High aerodynamic yaw loads coupled with electrical failures in the wind turbine can result to a slippage of the nacelle, due to limited braking capabilities of the yaw system. A slippage on the other hand can lead to a mechanical malfunction of the yaw system. To analyse the yawing characteristics of a wind turbine during nacelle slippage situations, a detailed multibody system model of the yaw system has been developed and incorporated in a multibody system model of a wind turbine based on a 3.3 MW turbine. Extreme load cases which lead to a nacelle slippage have been simulated. The dynamics and loads on different wind turbine components are presented and discussed. First results show minimal load increases of the rotor torque and the bending moments of the blade root sections during slippage but unfavourable rotational speeds of the yaw drives.

Analyses via automated mass spectrometry (MS/DS)

NASA Technical Reports Server (NTRS)

Koenig, T.

1985-01-01

New or improved uses of the Finnigan 4000 quadrupole mass spectrometer (MS) with its associated INCOS data system (DS) were investigated. The first phase involved an evaluative activity in which specific problems with miscalibration and gas chromatographic column conditioning were identified. This also revealed one solution to the problem of detection of substances not visible in the gas chromatography detection mode. A second phase was to seek useful applications of the direct inlet systems. This mode of sample introduction has not been previously utilized on the existing equipment and was successfully applied to the analysis of the components of TONOX 60/40 and in the thermal degradation products of some polymeric materials. Suggestions are made for improving and expanding the use of the MS/DS system in materials development and testing.

Multi-image mosaic with SIFT and vision measurement for microscale structures processed by femtosecond laser

NASA Astrophysics Data System (ADS)

Wang, Fu-Bin; Tu, Paul; Wu, Chen; Chen, Lei; Feng, Ding

2018-01-01

In femtosecond laser processing, the field of view of each image frame of the microscale structure is extremely small. In order to obtain the morphology of the whole microstructure, a multi-image mosaic with partially overlapped regions is required. In the present work, the SIFT algorithm for mosaic images was analyzed theoretically, and by using multiple images of a microgroove structure processed by femtosecond laser, a stitched image of the whole groove structure could be studied experimentally and realized. The object of our research concerned a silicon wafer with a microgroove structure ablated by femtosecond laser. First, we obtained microgrooves at a width of 380 μm at different depths. Second, based on the gray image of the microgroove, a multi-image mosaic with slot width and slot depth was realized. In order to improve the image contrast between the target and the background, and taking the slot depth image as an example, a multi-image mosaic was then realized using pseudo color enhancement. Third, in order to measure the structural size of the microgroove with the image, a known width streak ablated by femtosecond laser at 20 mW was used as a calibration sample. Through edge detection, corner extraction, and image correction for the streak images, we calculated the pixel width of the streak image and found the measurement ratio constant Kw in the width direction, and then obtained the proportional relationship between a pixel and a micrometer. Finally, circular spot marks ablated by femtosecond laser at 2 mW and 15 mW were used as test images, and proving that the value Kw was correct, the measurement ratio constant Kh in the height direction was obtained, and the image measurements for a microgroove of 380 × 117 μm was realized based on a measurement ratio constant Kw and Kh. The research and experimental results show that the image mosaic, image calibration, and geometric image parameter measurements for the microstructural image ablated by

Multiplex detection of quality indicator molecule targets in urine using programmable hairpin probes based on a simple double-T type microchip electrophoresis platform and isothermal polymerase-catalyzed target recycling.

PubMed

Zhou, Lingying; Gan, Ning; Wu, Yongxiang; Hu, Futao; Lin, Jianyuan; Cao, Yuting; Wu, Dazhen

2018-05-29

Recently, it has been crucial to be able to detect and quantify small molecular targets simultaneously in biological samples. Herein, a simple and conventional double-T type microchip electrophoresis (MCE) based platform for the multiplex detection of quality indicator molecule targets in urine, using ampicillin (AMPI), adenosine triphosphate (ATP) and estradiol (E2) as models, was developed. Several programmable hairpin probes (PHPs) were designed for detecting different targets and triggering isothermal polymerase-catalyzed target recycling (IPCTR) for signal amplification. Based on the target-responsive aptamer structure of PHP (Domain I), target recognition can induce PHP conformational transition and produce extension duplex DNA (dsDNA), assisted by primers & Bst polymerase. Afterwards, the target can be displaced to react with another PHP and initiate the next cycle. After several rounds of reaction, the dsDNA can be produced in large amounts by IPCTR. Three targets can be simultaneously converted to dsDNA fragments with different lengths, which can be separated and detected using MCE. Thus, a simple double-T type MCE based platform was successfully built for the homogeneous detection of multiplex targets in one channel. Under optimal conditions, the assay exhibited high throughput (48 samples per hour at most, not including reaction time) and sensitivity to three targets in urine with a detection limit of 1 nM (ATP), 0.05 nM (AMPI) and 0.1 nM (E2) respectively. The multiplex assay was successfully employed for the above three targets in several urine samples and combined the advantages of the high specificity of programmable hairpin probes, the excellent signal amplification of IPCTR, and the high through-put of MCE which can be employed for screening in biochemical analysis.

MW-assisted synthesis of SVO for ICD primary batteries

NASA Astrophysics Data System (ADS)

Beninati, Sabina; Fantuzzi, Matteo; Mastragostino, Marina; Soavi, Francesca

An Ag 2V 4O 11 (SVO) cathode material prepared by microwave (MW)-assisted solid-state synthesis (MW-SVO) was developed for lithium primary batteries for implantable cardioverter/defibrillators (ICDs). This paper presents the results of physical-chemical and electrochemical characterizations of MW-SVO as well as those of SVO prepared by conventional thermal route (T-SVO). A specific effect of MWs which accelerates the synthesis reaction and contributes to yield a material of different morphology and degree of crystallinity compared with those of T-SVO was observed. The results of pulsed electrochemical tests carried out at 37 °C in operative conditions of ICDs on Li/MW-SVO batteries with cathode mass loading sized for practical use are also reported. These tests demonstrated that MW-SVO can be used for high performing lithium primary battery delivering in few seconds the specific energy values required by ICD application.

75 FR 37519 - 30-Day Notice of Proposed Information Collection: Forms DS-4138, Request for Escort Screening...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-29

... to obtain or retain a benefit. Title of Information Collection: Application for OFM Web site Account...] 30-Day Notice of Proposed Information Collection: Forms DS-4138, Request for Escort Screening Courtesies; DS-4139, Photograph and Signature Card; & DS-4140, Application for OFM Web Site Account; DS- 1504...

Homogeneous and label-free electrochemiluminescence aptasensor based on the difference of electrostatic interaction and exonuclease-assisted target recycling amplification.

PubMed

Ni, Jiancong; Yang, Weiqiang; Wang, Qingxiang; Luo, Fang; Guo, Longhua; Qiu, Bin; Lin, Zhenyu; Yang, Huanghao

2018-05-15

The difference of electrostatic interaction between free Ru(phen) 3 2+ and Ru(phen) 3 2+ embedded in double strand DNA (dsDNA) to the negatively charged indium tin oxide (ITO) electrode has been applied to develop a homogeneous and label-free electrochemiluminescence (ECL) aptasensor for the first time. Ochratoxin A (OTA) has been chosen as the model target. The OTA aptamer is first hybridized with its complementary single strand DNA (ssDNA) to form dsDNA and then interacted with Ru(phen) 3 2+ via the grooves binding mode to form dsDNA-Ru(phen) 3 2+ complex, which remains negatively charged feature as well as low diffusion capacity to the negatively charged ITO electrode surface owing to the electrostatic repulsion. Meanwhile, the intercalated Ru(phen) 3 2+ in the grooves of dsDNA works as an ECL signal reporter instead of the labor-intensive labeling steps and can generate much more ECL signal than that from the labeling probe. In the presence of target, the aptamer prefers to form an aptamer-target complex in lieu of dsDNA, which induces the releasing of Ru(phen) 3 2+ from the dsDNA-Ru(phen) 3 2+ complex into the solution. With the assistance of RecJ f exonuclease (a ssDNA specific exonuclease), the released ssDNA and the aptamer in the target-complex were digested into mononucleotides. In the meantime, the target can be also liberated from OTA-aptamer complex and induce target cycling and large amount of free Ru(phen) 3 2+ present in the solution. Since Ru(phen) 3 2+ contains positive charges, which can diffuses easily to the ITO electrode surface because of electrostatic attraction, causing an obviously enhanced ECL signal detected. Under the optimal conditions, the enhanced ECL of the system has a linear relationship with the OTA concentration in the range of 0.01-1.0 ng/mL with a detection limit of 2 pg/mL. This innovative system not only expands the immobilization-free sensors in the electrochemiluminescent fields, but also can be developed for the

dsRNA binding characterization of full length recombinant wild type and mutants Zaire ebolavirus VP35.

PubMed

Zinzula, Luca; Esposito, Francesca; Pala, Daniela; Tramontano, Enzo

2012-03-01

The Ebola viruses (EBOVs) VP35 protein is a multifunctional major virulence factor involved in EBOVs replication and evasion of the host immune system. EBOV VP35 is an essential component of the viral RNA polymerase, it is a key participant of the nucleocapsid assembly and it inhibits the innate immune response by antagonizing RIG-I like receptors through its dsRNA binding function and, hence, by suppressing the host type I interferon (IFN) production. Insights into the VP35 dsRNA recognition have been recently revealed by structural and functional analysis performed on its C-terminus protein. We report the biochemical characterization of the Zaire ebolavirus (ZEBOV) full-length recombinant VP35 (rVP35)-dsRNA binding function. We established a novel in vitro magnetic dsRNA binding pull down assay, determined the rVP35 optimal dsRNA binding parameters, measured the rVP35 equilibrium dissociation constant for heterologous in vitro transcribed dsRNA of different length and short synthetic dsRNA of 8bp, and validated the assay for compound screening by assessing the inhibitory ability of auryntricarboxylic acid (IC(50) value of 50μg/mL). Furthermore, we compared the dsRNA binding properties of full length wt rVP35 with those of R305A, K309A and R312A rVP35 mutants, which were previously reported to be defective in dsRNA binding-mediated IFN inhibition, showing that the latter have measurably increased K(d) values for dsRNA binding and modified migration patterns in mobility shift assays with respect to wt rVP35. Overall, these results provide the first characterization of the full-length wt and mutants VP35-dsRNA binding functions. Copyright © 2012 Elsevier B.V. All rights reserved.

Antenna Allocation in MIMO Radar with Widely Separated Antennas for Multi-Target Detection

PubMed Central

Gao, Hao; Wang, Jian; Jiang, Chunxiao; Zhang, Xudong

2014-01-01

In this paper, we explore a new resource called multi-target diversity to optimize the performance of multiple input multiple output (MIMO) radar with widely separated antennas for detecting multiple targets. In particular, we allocate antennas of the MIMO radar to probe different targets simultaneously in a flexible manner based on the performance metric of relative entropy. Two antenna allocation schemes are proposed. In the first scheme, each antenna is allocated to illuminate a proper target over the entire illumination time, so that the detection performance of each target is guaranteed. The problem is formulated as a minimum makespan scheduling problem in the combinatorial optimization framework. Antenna allocation is implemented through a branch-and-bound algorithm and an enhanced factor 2 algorithm. In the second scheme, called antenna-time allocation, each antenna is allocated to illuminate different targets with different illumination time. Both antenna allocation and time allocation are optimized based on illumination probabilities. Over a large range of transmitted power, target fluctuations and target numbers, both of the proposed antenna allocation schemes outperform the scheme without antenna allocation. Moreover, the antenna-time allocation scheme achieves a more robust detection performance than branch-and-bound algorithm and the enhanced factor 2 algorithm when the target number changes. PMID:25350505

Antenna allocation in MIMO radar with widely separated antennas for multi-target detection.

PubMed

Gao, Hao; Wang, Jian; Jiang, Chunxiao; Zhang, Xudong

2014-10-27

In this paper, we explore a new resource called multi-target diversity to optimize the performance of multiple input multiple output (MIMO) radar with widely separated antennas for detecting multiple targets. In particular, we allocate antennas of the MIMO radar to probe different targets simultaneously in a flexible manner based on the performance metric of relative entropy. Two antenna allocation schemes are proposed. In the first scheme, each antenna is allocated to illuminate a proper target over the entire illumination time, so that the detection performance of each target is guaranteed. The problem is formulated as a minimum makespan scheduling problem in the combinatorial optimization framework. Antenna allocation is implemented through a branch-and-bound algorithm and an enhanced factor 2 algorithm. In the second scheme, called antenna-time allocation, each antenna is allocated to illuminate different targets with different illumination time. Both antenna allocation and time allocation are optimized based on illumination probabilities. Over a large range of transmitted power, target fluctuations and target numbers, both of the proposed antenna allocation schemes outperform the scheme without antenna allocation. Moreover, the antenna-time allocation scheme achieves a more robust detection performance than branch-and-bound algorithm and the enhanced factor 2 algorithm when the target number changes.

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9)

PubMed Central

Fu, Qinqin; Yuan, Y. Adam

2013-01-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA. PMID:23361462

Structural insights into RISC assembly facilitated by dsRNA-binding domains of human RNA helicase A (DHX9).

PubMed

Fu, Qinqin; Yuan, Y Adam

2013-03-01

Intensive research interest has focused on small RNA-processing machinery and the RNA-induced silencing complex (RISC), key cellular machines in RNAi pathways. However, the structural mechanism regarding RISC assembly, the primary step linking small RNA processing and RNA-mediated gene silencing, is largely unknown. Human RNA helicase A (DHX9) was reported to function as an RISC-loading factor, and such function is mediated mainly by its dsRNA-binding domains (dsRBDs). Here, we report the crystal structures of human RNA helicase A (RHA) dsRBD1 and dsRBD2 domains in complex with dsRNAs, respectively. Structural analysis not only reveals higher siRNA duplex-binding affinity displayed by dsRBD1, but also identifies a crystallographic dsRBD1 pair of physiological significance in cooperatively recognizing dsRNAs. Structural observations are further validated by isothermal titration calorimetric (ITC) assay. Moreover, co-immunoprecipitation (co-IP) assay coupled with mutagenesis demonstrated that both dsRBDs are required for RISC association, and such association is mediated by dsRNA. Hence, our structural and functional efforts have revealed a potential working model for siRNA recognition by RHA tandem dsRBDs, and together they provide direct structural insights into RISC assembly facilitated by RHA.

trans- cis Isomerism and acylimine formation in DsRed chromophore models: Intrinsic rotation barriers

NASA Astrophysics Data System (ADS)

Olsen, Seth; Smith, Sean C.

2006-07-01

The chromophore of the red fluorescent protein DsRed contains an acylimine substituent to a GFP-like chromophore structure. The acylimine is formed from the trans peptide linkage between residues F65 and Q66 in immature DsRed, but has a cis configuration in the mature protein. The relationship between acylimine formation and trans- cis isomerization is unresolved. We have calculated bond rotation profiles for models of mature and immature DsRed chromophores using B3LYP DFT. The isomerization barrier is substantially reduced in acylimine-substituted models, providing prima facie evidence that acylimine formation precedes trans- cis isomerization in DsRed chromophores.

Strong decays of DJ(3000 ) and Ds J(3040 )

NASA Astrophysics Data System (ADS)

Li, Si-Chen; Wang, Tianhong; Jiang, Yue; Tan, Xiao-Ze; Li, Qiang; Wang, Guo-Li; Chang, Chao-Hsi

2018-03-01

In this paper, we systematically calculate two-body strong decays of newly observed DJ(3000 ) and Ds J(3040 ) with 2 P (1+) and 2 P (1+') assignments in an instantaneous approximation of the Bethe-Salpeter equation method. Our results show that both resonances can be explained as the 2 P (1+') with broad width via 3P1 and 1P1 mixing in D and Ds families. For DJ(3000 ), the total width is 229.6 MeV in our calculation, close to the upper limit of experimental data, and the dominant decay channels are D2*π , D*π , and D*(2600 )π . For Ds J(3040 ), the total width is 157.4 MeV in our calculation, close to the lower limit of experimental data, and the dominant channels are D*K and D*K*. These results are consistent with observed channels in experiments. Given the very little information that has been obtained from experiments and the large error bars of the total decay widths, we recommend the detection of dominant channels in our calculation.

KiDS-450: testing extensions to the standard cosmological model

NASA Astrophysics Data System (ADS)

Joudaki, Shahab; Mead, Alexander; Blake, Chris; Choi, Ami; de Jong, Jelte; Erben, Thomas; Fenech Conti, Ian; Herbonnet, Ricardo; Heymans, Catherine; Hildebrandt, Hendrik; Hoekstra, Henk; Joachimi, Benjamin; Klaes, Dominik; Köhlinger, Fabian; Kuijken, Konrad; McFarland, John; Miller, Lance; Schneider, Peter; Viola, Massimo

2017-10-01

We test extensions to the standard cosmological model with weak gravitational lensing tomography using 450 deg2 of imaging data from the Kilo Degree Survey (KiDS). In these extended cosmologies, which include massive neutrinos, non-zero curvature, evolving dark energy, modified gravity and running of the scalar spectral index, we also examine the discordance between KiDS and cosmic microwave background (CMB) measurements from Planck. The discordance between the two data sets is largely unaffected by a more conservative treatment of the lensing systematics and the removal of angular scales most sensitive to non-linear physics. The only extended cosmology that simultaneously alleviates the discordance with Planck and is at least moderately favoured by the data includes evolving dark energy with a time-dependent equation of state (in the form of the w0 - wa parametrization). In this model, the respective S_8=σ _8√{Ω m/0.3} constraints agree at the 1σ level, and there is 'substantial concordance' between the KiDS and Planck data sets when accounting for the full parameter space. Moreover, the Planck constraint on the Hubble constant is wider than in Λ cold dark matter (ΛCDM) and in agreement with the Riess et al. (2016) direct measurement of H0. The dark energy model is moderately favoured as compared to ΛCDM when combining the KiDS and Planck measurements, and marginalized constraints in the w0-wa plane are discrepant with a cosmological constant at the 3σ level. KiDS further constrains the sum of neutrino masses to 4.0 eV (95% CL), finds no preference for time or scale-dependent modifications to the metric potentials, and is consistent with flatness and no running of the spectral index.

Concentrating Solar Power Projects - Urat 50MW Fresnel CSP project |

Science.gov Websites

Concentrating Solar Power | NREL 50MW Fresnel CSP project Status Date: September 29, 2016 Turbine Capacity: Net: 50.0 MW Gross: 50.0 MW Status: Under development Do you have more information , corrections, or comments? Background Technology: Linear Fresnel reflector Status: Under development Country

Leptonic decays of charged D and Ds mesons

NASA Astrophysics Data System (ADS)

Menaa, Nabil

Using 281 pb--1 of data taken on the psi(3770) resonance and 314 pb--1 of data near or at 4170 MeV collected with the CLEO-c detector, we present two analyses to study the purely leptonic decays of charmed and charmed strange charged mesons. In the first analysis, we extract a relatively precise value for the decay constant of the D+ meson by measuring B (D+ → mu+nu) = (4.40 +/- 0.66+0.09-0.12 ) x 10-4. We find fD + = (222.6 +/- 16.7+2.8-3.4 ) MeV, and compare with current theoretical calculations. We also set a 90% confidence upper limit on B (D+ → e +nu) < 2.4 x 10-5 which constrains new physics models. Finally with this data sample, we test whether or not the tau lepton manifests the same couplings as the mu lepton by investigating the relative decay rates in purely leptonic D+ meson decays. We limit B (D+ → tau+nu) < 2.1 x 10--3 at 90% confidence level (C. L.), thus allowing us to place the first upper limit on the ratio R = Gamma (D+ → tau+nu)/Gamma( D+ → mu+nu). The ratio of R to the Standard Model expectation of 2.65 then is <1.8 at 90% C. L., consistent with the prediction of lepton universality. In the second analysis, we examine e+ e-- → D-sD*+s and D-*sD+s interactions at 4170 MeV using the CLEO-c detector in order to measure the decay constant fD+s . We use the D+s → ℓ+nu channel, where the ℓ+ designates either a mu+ or a tau+, when the tau+ → pi+nu. Analyzing both modes independently, we determine B ( D+s → mu+nu) = (0.594 +/- 0.066 +/- 0.031)%, B ( D+s → tau+nu) = (8.0 +/- 1.3 +/- 0.4)%. We also analyze them simultaneously to find an effective value of B ( D+s → mu+nu) = (0.621 +/- 0.058 +/- 0.032)% and extract fD+s = 270 +/- 13 +/- 7 MeV. Combining with our previous determination of B (D+ → mu+nu), we also find the ratio fD+s/fD+ = 1.21 +/- 0.11 +/- 0.04. We compare with current theoretical estimates. Finally, we limit B ( D+s → e+nu) < 1.3 x 10 --4 at 90% confidence level.

Effects of multi-stakeholder platforms on multi-stakeholder innovation networks: Implications for research for development interventions targeting innovations at scale

PubMed Central

Schut, Marc; Hermans, Frans; van Asten, Piet; Leeuwis, Cees

2018-01-01

Multi-stakeholder platforms (MSPs) have been playing an increasing role in interventions aiming to generate and scale innovations in agricultural systems. However, the contribution of MSPs in achieving innovations and scaling has been varied, and many factors have been reported to be important for their performance. This paper aims to provide evidence on the contribution of MSPs to innovation and scaling by focusing on three developing country cases in Burundi, Democratic Republic of Congo, and Rwanda. Through social network analysis and logistic models, the paper studies the changes in the characteristics of multi-stakeholder innovation networks targeted by MSPs and identifies factors that play significant roles in triggering these changes. The results demonstrate that MSPs do not necessarily expand and decentralize innovation networks but can lead to contraction and centralization in the initial years of implementation. They show that some of the intended next users of interventions with MSPs–local-level actors–left the innovation networks, whereas the lead organization controlling resource allocation in the MSPs substantially increased its centrality. They also indicate that not all the factors of change in innovation networks are country specific. Initial conditions of innovation networks and funding provided by the MSPs are common factors explaining changes in innovation networks across countries and across different network functions. The study argues that investigating multi-stakeholder innovation network characteristics targeted by the MSP using a network approach in early implementation can contribute to better performance in generating and scaling innovations, and that funding can be an effective implementation tool in developing country contexts. PMID:29870559

Effects of multi-stakeholder platforms on multi-stakeholder innovation networks: Implications for research for development interventions targeting innovations at scale.

PubMed

Sartas, Murat; Schut, Marc; Hermans, Frans; Asten, Piet van; Leeuwis, Cees

2018-01-01

Multi-stakeholder platforms (MSPs) have been playing an increasing role in interventions aiming to generate and scale innovations in agricultural systems. However, the contribution of MSPs in achieving innovations and scaling has been varied, and many factors have been reported to be important for their performance. This paper aims to provide evidence on the contribution of MSPs to innovation and scaling by focusing on three developing country cases in Burundi, Democratic Republic of Congo, and Rwanda. Through social network analysis and logistic models, the paper studies the changes in the characteristics of multi-stakeholder innovation networks targeted by MSPs and identifies factors that play significant roles in triggering these changes. The results demonstrate that MSPs do not necessarily expand and decentralize innovation networks but can lead to contraction and centralization in the initial years of implementation. They show that some of the intended next users of interventions with MSPs-local-level actors-left the innovation networks, whereas the lead organization controlling resource allocation in the MSPs substantially increased its centrality. They also indicate that not all the factors of change in innovation networks are country specific. Initial conditions of innovation networks and funding provided by the MSPs are common factors explaining changes in innovation networks across countries and across different network functions. The study argues that investigating multi-stakeholder innovation network characteristics targeted by the MSP using a network approach in early implementation can contribute to better performance in generating and scaling innovations, and that funding can be an effective implementation tool in developing country contexts.

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

PubMed

Vinay, Keshavamurthy; Narang, Tarun; Saikia, Uma N; Kumaran, Muthu Sendhil; Dogra, Sunil

2017-03-01

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation. © 2016 Wiley Periodicals, Inc.

Concentrating Solar Power Projects - Dacheng Dunhuang 50MW Molten Salt

Science.gov Websites

project Status Date: September 29, 2016 Project Overview Project Name: Dacheng Dunhuang 50MW Molten Salt ., Ltd Technology: Linear Fresnel reflector Turbine Capacity: Net: 50.0 MW Gross: 50.0 MW Status: Under reflector Status: Under development Country: China City: Dunhuang Region: Gansu Province Contact(s

Concentrating Solar Power Projects - Chabei 64MW Molten Salt Parabolic

Science.gov Websites

project Status Date: September 29, 2016 Project Overview Project Name: Chabei 64MW Molten Salt Parabolic Technology: Parabolic trough Turbine Capacity: Net: 64.0 MW Gross: 64.0 MW Status: Under development Do you have more information, corrections, or comments? Background Technology: Parabolic trough Status: Under

Characterization of cellulose acetates according to DS and molar mass using two-dimensional chromatography.

PubMed

Ghareeb, Hewa Othman; Radke, Wolfgang

2013-11-06

A two-dimensional liquid chromatographic method (2D LC) was developed to analyze the heterogeneities of cellulose acetates (CA) in the DS-range DS=1.5-2.9 with respect to both, molar mass and degree of substitution (DS). The method uses gradient liquid chromatography (HPLC) as the first dimension in order to separate by DS followed by separation of the different fractions by size (SEC) in the second dimension. The 2D experiments revealed different correlations between gradient and SEC elution volume. These correlations might arise from differences in the synthetic conditions. The newly developed 2D LC separation therefore provides new insights into the heterogeneity of CAs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.

PubMed

Shallev, Lea; Kopel, Eli; Feiglin, Ariel; Leichner, Gil S; Avni, Dror; Sidi, Yechezkel; Eisenberg, Eli; Barzilai, Aviv; Levanon, Erez Y; Greenberger, Shoshana

2018-06-01

Recognition of dsRNA molecules activates the MDA5-MAVS pathway and plays a critical role in stimulating type-I interferon responses in psoriasis. However, the source of the dsRNA accumulation in psoriatic keratinocytes remains largely unknown. A-to-I RNA editing is a common co- or post-transcriptional modification that diversifies adenosine in dsRNA, and leads to unwinding of dsRNA structures. Thus, impaired RNA editing activity can result in an increased load of endogenous dsRNAs. Here we provide a transcriptome-wide analysis of RNA editing across dozens of psoriasis patients, and we demonstrate a global editing reduction in psoriatic lesions. In addition to the global alteration, we also detect editing changes in functional recoding sites located in the IGFBP7 , COPA , and FLNA genes. Accretion of dsRNA activates autoimmune responses, and therefore the results presented here, linking for the first time an autoimmune disease to reduction in global editing level, are relevant to a wide range of autoimmune diseases. © 2018 Shallev et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Multi-target detection and positioning in crowds using multiple camera surveillance

NASA Astrophysics Data System (ADS)

Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

2018-04-01

In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

Design of the LBNF Beamline Target Station

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

Tariq, S.; Ammigan, K.; Anderson, K.

2016-10-01

The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding inmore » a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.« less

Internet Voice Distribution System (IVoDS) Utilization in Remote Payload Operations

NASA Technical Reports Server (NTRS)

Best, Susan; Bradford, Bob; Chamberlain, Jim; Nichols, Kelvin; Bailey, Darrell (Technical Monitor)

2002-01-01

Due to limited crew availability to support science and the large number of experiments to be operated simultaneously, telescience is key to a successful International Space Station (ISS) science program. Crew, operations personnel at NASA centers, and researchers at universities and companies around the world must work closely together to perform scientific experiments on-board ISS. NASA has initiated use of Voice over Internet Protocol (VoIP) to supplement the existing HVoDS mission voice communications system used by researchers. The Internet Voice Distribution System (IVoDS) connects researchers to mission support "loops" or conferences via Internet Protocol networks such as the high-speed Internet 2. Researchers use IVoDS software on personal computers to talk with operations personnel at NASA centers. IVoDS also has the capability, if authorized, to allow researchers to communicate with the ISS crew during experiment operations. NODS was developed by Marshall Space Flight Center with contractors A2 Technology, Inc. FVC, Lockheed- Martin, and VoIP Group. IVoDS is currently undergoing field-testing with full deployment for up to 50 simultaneous users expected in 2002. Research is currently being performed to take full advantage of the digital world - the Personal Computer and Internet Protocol networks - to qualitatively enhance communications among ISS operations personnel. In addition to the current voice capability, video and data-sharing capabilities are being investigated. Major obstacles being addressed include network bandwidth capacity and strict security requirements. Techniques being investigated to reduce and overcome these obstacles include emerging audio-video protocols and network technology including multicast and quality-of-service.

15 MW HArdware-in-the-loop Grid Simulation Project

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

Rigas, Nikolaos; Fox, John Curtiss; Collins, Randy

2014-10-31

The 15MW Hardware-in-the-loop (HIL) Grid Simulator project was to (1) design, (2) construct and (3) commission a state-of-the-art grid integration testing facility for testing of multi-megawatt devices through a ‘shared facility’ model open to all innovators to promote the rapid introduction of new technology in the energy market to lower the cost of energy delivered. The 15 MW HIL Grid Simulator project now serves as the cornerstone of the Duke Energy Electric Grid Research, Innovation and Development (eGRID) Center. This project leveraged the 24 kV utility interconnection and electrical infrastructure of the US DOE EERE funded WTDTF project at themore » Clemson University Restoration Institute in North Charleston, SC. Additionally, the project has spurred interest from other technology sectors, including large PV inverter and energy storage testing and several leading edge research proposals dealing with smart grid technologies, grid modernization and grid cyber security. The key components of the project are the power amplifier units capable of providing up to 20MW of defined power to the research grid. The project has also developed a one of a kind solution to performing fault ride-through testing by combining a reactive divider network and a large power converter into a hybrid method. This unique hybrid method of performing fault ride-through analysis will allow for the research team at the eGRID Center to investigate the complex differences between the alternative methods of performing fault ride-through evaluations and will ultimately further the science behind this testing. With the final goal of being able to perform HIL experiments and demonstration projects, the eGRID team undertook a significant challenge with respect to developing a control system that is capable of communicating with several different pieces of equipment with different communication protocols in real-time. The eGRID team developed a custom fiber optical network that is based

A Proton Flare Triggered the Mw 8.1 Chiapos Mexican Earthquake

NASA Astrophysics Data System (ADS)

Elfaki, H.; Yousef, S.

2017-12-01

In a 2015 Cairo University M.Sc. thesis by Sarah Khodairy, very strong earthquakes were found to be highly correlated with proton flares. Strange blue and green bright flashes of light across Mexico accompanied the 8th of September 2017 Mw 1.8 Chiapas earthquake. Those lights were contemporary with a solar proton flare. Those green and blue lights are indicative of the arrival of proton streams over Mexico and their interaction with atmospheric Oxygen and Nitrogen atoms respectively in analogy with aurora lights. The proton streams attacked the weak spots of tectonic plates where the Coscos plate is being subducted below the North American plate. It is suggested that they induced telluric electric currents in the ground and in the magma thus caused motion and more subduction in the tectonic plates. Such motion immediately trigged the Chiapas earthquake in the near vicinity. The Bz component of the interplanetary magnetic field was highly negative, a door was opened in the magnetosphere and the proton stream easily leaked inside and targeted Mexico. This proton flare was accompanied by coronal mass ejection and extremely strong X.9.3- class X-ray flare as well as magnetic storms. On the other hand, the 19th of September Mw 7.1 Puebla central Mexico earthquake was initiated by fast solar wind coronal hole stream. Such stream if they hit ground they cause earthquakes, if they hit narrow seas like the Red Sea they cause flash floods. However if they target Oceans they initiate hurricanes.

Heart failure: a weak link in CHA2 DS2 -VASc.

PubMed

Friberg, Leif; Lund, Lars H

2018-06-01

In atrial fibrillation, stroke risk is assessed by the CHA 2 DS 2 -VASc score. Heart failure is included in CHA 2 DS 2 -VASc, but the rationale is uncertain. Our objective was to test if heart failure is a risk factor for stroke, independent of other risk factors in CHA 2 DS 2 -VASc. We studied 300 839 patients with atrial fibrillation in the Swedish Patient Register 2005-11. Three definitions of heart failure were used in order to assess the robustness of the results. In the main analysis, heart failure was defined by a hospital discharge diagnosis of heart failure as first or second diagnosis and a filled prescription of a diuretic within 3 months before index + 30 days. The second definition counted first or second discharge diagnoses <1 year before index + 30 days and the third definition any heart failure diagnosis in open or hospital care before index + 30 days. Associations with outcomes were assessed with multivariable Cox analyses. Patients with heart failure were older (80.5 vs. 74.0 years, P < 0.001) and had higher CHA 2 DS 2 -VASc score (4.4 vs. 2.7, P < 0.001). The 1 year incidence of ischaemic stroke without warfarin was 4.4% with heart failure and 3.1% without. Adjustment for the cofactors in CHA 2 DS 2 -VASc eradicated the difference in stroke risk between patients with and without heart failure (hazard ratio 1.01 with 95% confidence interval 0.96-1.05). The area under the receiver operating characteristic curve for CHA 2 DS 2 -VASc was not improved by points for heart failure. A clinical diagnosis of heart failure was not an independent risk factor for stroke in patients with atrial fibrillation, which may have implications for anticoagulation management. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Phosphoric acid fuel cell 1.3 MW plant in Milan

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

Colombo, M.; Vigano, A.

1997-07-01

At the end of the 80`s Aem, ENEA and Ansaldo Ricerche began to design and build a 1.3 MW phosphoric-acid-fuel-cell power plant for the production of electrical power and heat; this plant was built and installed in the Bicocca site, in the north-east area of Milan, where a great development is being promoted. Aem has been taking over the plant since July 1995. Its aim is to test the extensively advantages of this technology for both conversion efficiency and low environmental impact. The experimentation will have to recognize the key elements in order to plan and create the multi-megawatt plantsmore » with the phosphoric acid technology, opening the experimentation to international partners, like users, industries and Universities interested in the development and the application of these new systems of energy cogeneration.« less

CasA mediates Cas3-catalyzed target degradation during CRISPR RNA-guided interference.

PubMed

Hochstrasser, Megan L; Taylor, David W; Bhat, Prashant; Guegler, Chantal K; Sternberg, Samuel H; Nogales, Eva; Doudna, Jennifer A

2014-05-06

In bacteria, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) DNA-targeting complex Cascade (CRISPR-associated complex for antiviral defense) uses CRISPR RNA (crRNA) guides to bind complementary DNA targets at sites adjacent to a trinucleotide signature sequence called the protospacer adjacent motif (PAM). The Cascade complex then recruits Cas3, a nuclease-helicase that catalyzes unwinding and cleavage of foreign double-stranded DNA (dsDNA) bearing a sequence matching that of the crRNA. Cascade comprises the CasA-E proteins and one crRNA, forming a structure that binds and unwinds dsDNA to form an R loop in which the target strand of the DNA base pairs with the 32-nt RNA guide sequence. Single-particle electron microscopy reconstructions of dsDNA-bound Cascade with and without Cas3 reveal that Cascade positions the PAM-proximal end of the DNA duplex at the CasA subunit and near the site of Cas3 association. The finding that the DNA target and Cas3 colocalize with CasA implicates this subunit in a key target-validation step during DNA interference. We show biochemically that base pairing of the PAM region is unnecessary for target binding but critical for Cas3-mediated degradation. In addition, the L1 loop of CasA, previously implicated in PAM recognition, is essential for Cas3 activation following target binding by Cascade. Together, these data show that the CasA subunit of Cascade functions as an essential partner of Cas3 by recognizing DNA target sites and positioning Cas3 adjacent to the PAM to ensure cleavage.

Description of an 8 MW reference wind turbine

NASA Astrophysics Data System (ADS)

Desmond, Cian; Murphy, Jimmy; Blonk, Lindert; Haans, Wouter

2016-09-01

An 8 MW wind turbine is described in terms of mass distribution, dimensions, power curve, thrust curve, maximum design load and tower configuration. This turbine has been described as part of the EU FP7 project LEANWIND in order to facilitate research into logistics and naval architecture efficiencies for future offshore wind installations. The design of this 8 MW reference wind turbine has been checked and validated by the design consultancy DNV-GL. This turbine description is intended to bridge the gap between the NREL 5 MW and DTU 10 reference turbines and thus contribute to the standardisation of research and development activities in the offshore wind energy industry.

Computer-aided design of multi-target ligands at A1R, A2AR and PDE10A, key proteins in neurodegenerative diseases.

PubMed

Kalash, Leen; Val, Cristina; Azuaje, Jhonny; Loza, María I; Svensson, Fredrik; Zoufir, Azedine; Mervin, Lewis; Ladds, Graham; Brea, José; Glen, Robert; Sotelo, Eddy; Bender, Andreas

2017-12-30

Compounds designed to display polypharmacology may have utility in treating complex diseases, where activity at multiple targets is required to produce a clinical effect. In particular, suitable compounds may be useful in treating neurodegenerative diseases by promoting neuronal survival in a synergistic manner via their multi-target activity at the adenosine A 1 and A 2A receptors (A 1 R and A 2A R) and phosphodiesterase 10A (PDE10A), which modulate intracellular cAMP levels. Hence, in this work we describe a computational method for the design of synthetically feasible ligands that bind to A 1 and A 2A receptors and inhibit phosphodiesterase 10A (PDE10A), involving a retrosynthetic approach employing in silico target prediction and docking, which may be generally applicable to multi-target compound design at several target classes. This approach has identified 2-aminopyridine-3-carbonitriles as the first multi-target ligands at A 1 R, A 2A R and PDE10A, by showing agreement between the ligand and structure based predictions at these targets. The series were synthesized via an efficient one-pot scheme and validated pharmacologically as A 1 R/A 2A R-PDE10A ligands, with IC 50 values of 2.4-10.0 μM at PDE10A and K i values of 34-294 nM at A 1 R and/or A 2A R. Furthermore, selectivity profiling of the synthesized 2-amino-pyridin-3-carbonitriles against other subtypes of both protein families showed that the multi-target ligand 8 exhibited a minimum of twofold selectivity over all tested off-targets. In addition, both compounds 8 and 16 exhibited the desired multi-target profile, which could be considered for further functional efficacy assessment, analog modification for the improvement of selectivity towards A 1 R, A 2A R and PDE10A collectively, and evaluation of their potential synergy in modulating cAMP levels.

Incidence of diverse dsRNA mycoviruses in Trichoderma spp. causing green mold disease of shiitake Lentinula edodes.

PubMed

Yun, Suk-Hyun; Lee, Song Hee; So, Kum-Kang; Kim, Jung-Mi; Kim, Dae-Hyuk

2016-09-22

A total of 315 fungal isolates causing green mold disease were collected from contaminated artificial logs and sawdust bags used for cultivating shiitake Lentinula edodes in Korea and were analyzed for the presence of double-stranded RNA (dsRNA). dsRNA, which was purified using dsRNA-specific chromatography and verified by dsRNA-specific RNaseIII digestion, was detected in 32 isolates. The molecular taxonomy of dsRNA-infected isolates indicated that all isolates belonged to the Trichoderma spp.. The number and size of dsRNAs varied among isolates and the band patterns could be categorized into 15 groups. Although there were seven dsRNA groups observed in multiple isolates, eight groups were found to occur in single isolates. The most common dsRNA group, group VI, which contained a band of 10 kb, occurred in 10 isolates encompassing three species of Trichoderma Partial sequence analysis of two selected dsRNA groups revealed a high degree of similarity to sequences of a RNA-dependent RNA polymerase, hypothetical protein, and polyprotein genes of other hypoviruses such as Macrophomina phaseolina hypovirus 1, Trichoderma hypovirus, and Fusarium graminearum hypovirus 2, respectively, indicating the occurrence of mycoviruses in Trichoderma spp.. Northern blot analysis suggested that many different mycoviruses, which have not been identified yet, exist in Trichoderma. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Visualizing double-stranded RNA distribution and dynamics in living cells by dsRNA binding-dependent fluorescence complementation

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

Cheng, Xiaofei; College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang 310036; Deng, Ping

Double-stranded RNA (dsRNA) is an important type of RNA that plays essential roles in diverse cellular processes in eukaryotic organisms and a hallmark in infections by positive-sense RNA viruses. Currently, no in vivo technology has been developed for visualizing dsRNA in living cells. Here, we report a dsRNA binding-dependent fluorescence complementation (dRBFC) assay that can be used to efficiently monitor dsRNA distribution and dynamics in vivo. The system consists of two dsRNA-binding proteins, which are fused to the N- and C-terminal halves of the yellow fluorescent protein (YFP). Binding of the two fusion proteins to a common dsRNA brings themore » split YFP halves in close proximity, leading to the reconstitution of the fluorescence-competent structure and restoration of fluorescence. Using this technique, we were able to visualize the distribution and trafficking of the replicative RNA intermediates of positive-sense RNA viruses in living cells. - Highlights: • A live-cell imaging system was developed for visualizing dsRNA in vivo. • It uses dsRNA binding proteins fused with two halves of a fluorescent protein. • Binding to a common dsRNA enables the reporter to become fluorescent. • The system can efficiently monitor viral RNA replication in living cells.« less

Development of 70 MW class superconducting generator with quick-response excitation

NASA Astrophysics Data System (ADS)

Miyaike, Kiyoshi; Kitajima, Toshio; Ito, Tetsuo

2002-03-01

The development of a superconducting generator had been carried out for 12 years under the first stage of a Super GM project. The 70 MW class model machine with quick response excitation was manufactured and evaluated in the project. This type of superconducting generator improves power system stability against rapid load fluctuations at the power system faults. This model machine achieved all development targets including high stability during rapid excitation control. It was also connected to the actual 77 kV electrical power grid as a synchronous condenser and proved advantages and high-operation reliability of the superconducting generator.

Profile of Ph.Ds in Canada.

ERIC Educational Resources Information Center

von Zur-Muehlen, Max

A profile of the socio-economic characteristics of the permanent residents of Canada holding an earned doctorate is presented. In 1973, there were 27,410 Canadian residents who had obtained an earned doctorate. (Holders of such professional doctoral degrees as Doctor of Medicine are excluded from this study.) Only 9 percent of the Ph.Ds were…

ROBIN: a platform for evaluating automatic target recognition algorithms: II. Protocols used for evaluating algorithms and results obtained on the SAGEM DS database

NASA Astrophysics Data System (ADS)

Duclos, D.; Lonnoy, J.; Guillerm, Q.; Jurie, F.; Herbin, S.; D'Angelo, E.

2008-04-01

Over the five past years, the computer vision community has explored many different avenues of research for Automatic Target Recognition. Noticeable advances have been made and we are now in the situation where large-scale evaluations of ATR technologies have to be carried out, to determine what the limitations of the recently proposed methods are and to determine the best directions for future works. ROBIN, which is a project funded by the French Ministry of Defence and by the French Ministry of Research, has the ambition of being a new reference for benchmarking ATR algorithms in operational contexts. This project, headed by major companies and research centers involved in Computer Vision R&D in the field of Defense (Bertin Technologies, CNES, ECA, DGA, EADS, INRIA, ONERA, MBDA, SAGEM, THALES) recently released a large dataset of several thousands of hand-annotated infrared and RGB images of different targets in different situations. Setting up an evaluation campaign requires us to define, accurately and carefully, sets of data (both for training ATR algorithms and for their evaluation), tasks to be evaluated, and finally protocols and metrics for the evaluation. ROBIN offers interesting contributions to each one of these three points. This paper first describes, justifies and defines the set of functions used in the ROBIN competitions and relevant for evaluating ATR algorithms (Detection, Localization, Recognition and Identification). It also defines the metrics and the protocol used for evaluating these functions. In the second part of the paper, the results obtained by several state-of-the-art algorithms on the SAGEM DS database (a subpart of ROBIN) are presented and discussed

Global calibration of multi-cameras with non-overlapping fields of view based on photogrammetry and reconfigurable target

NASA Astrophysics Data System (ADS)

Xia, Renbo; Hu, Maobang; Zhao, Jibin; Chen, Songlin; Chen, Yueling

2018-06-01

Multi-camera vision systems are often needed to achieve large-scale and high-precision measurement because these systems have larger fields of view (FOV) than a single camera. Multiple cameras may have no or narrow overlapping FOVs in many applications, which pose a huge challenge to global calibration. This paper presents a global calibration method for multi-cameras without overlapping FOVs based on photogrammetry technology and a reconfigurable target. Firstly, two planar targets are fixed together and made into a long target according to the distance between the two cameras to be calibrated. The relative positions of the two planar targets can be obtained by photogrammetric methods and used as invariant constraints in global calibration. Then, the reprojection errors of target feature points in the two cameras’ coordinate systems are calculated at the same time and optimized by the Levenberg–Marquardt algorithm to find the optimal solution of the transformation matrix between the two cameras. Finally, all the camera coordinate systems are converted to the reference coordinate system in order to achieve global calibration. Experiments show that the proposed method has the advantages of high accuracy (the RMS error is 0.04 mm) and low cost and is especially suitable for on-site calibration.

A Student’s t Mixture Probability Hypothesis Density Filter for Multi-Target Tracking with Outliers

PubMed Central

Liu, Zhuowei; Chen, Shuxin; Wu, Hao; He, Renke; Hao, Lin

2018-01-01

In multi-target tracking, the outliers-corrupted process and measurement noises can reduce the performance of the probability hypothesis density (PHD) filter severely. To solve the problem, this paper proposed a novel PHD filter, called Student’s t mixture PHD (STM-PHD) filter. The proposed filter models the heavy-tailed process noise and measurement noise as a Student’s t distribution as well as approximates the multi-target intensity as a mixture of Student’s t components to be propagated in time. Then, a closed PHD recursion is obtained based on Student’s t approximation. Our approach can make full use of the heavy-tailed characteristic of a Student’s t distribution to handle the situations with heavy-tailed process and the measurement noises. The simulation results verify that the proposed filter can overcome the negative effect generated by outliers and maintain a good tracking accuracy in the simultaneous presence of process and measurement outliers. PMID:29617348

Powerful inner/outer controlled multi-target magnetic nanoparticle drug carrier prepared by liquid photo-immobilization

NASA Astrophysics Data System (ADS)

Guan, Yan-Qing; Zheng, Zhe; Huang, Zheng; Li, Zhibin; Niu, Shuiqin; Liu, Jun-Ming

2014-05-01

Nanomagnetic materials offer exciting avenues for advancing cancer therapies. Most researches have focused on efficient delivery of drugs in the body by incorporating various drug molecules onto the surface of nanomagnetic particles. The challenge is how to synthesize low toxic nanocarriers with multi-target drug loading. The cancer cell death mechanisms associated with those nanocarriers remain unclear either. Following the cell biology mechanisms, we develop a liquid photo-immobilization approach to attach doxorubicin, folic acid, tumor necrosis factor-α, and interferon-γ onto the oleic acid molecules coated Fe3O4 magnetic nanoparticles to prepare a kind of novel inner/outer controlled multi-target magnetic nanoparticle drug carrier. In this work, this approach is demonstrated by a variety of structural and biomedical characterizations, addressing the anti-cancer effects in vivo and in vitro on the HeLa, and it is highly efficient and powerful in treating cancer cells in a valuable programmed cell death mechanism for overcoming drug resistance.

New materials for high temperature turbines; ONERA's DS composites confronted with blade problems

NASA Technical Reports Server (NTRS)

Bibring, H.

1977-01-01

ONERA's refractory DS composites were cited as materials required for use in advanced aircraft turbines, operating at high temperatures. These materials were found to be reliable in the construction of turbine blades. Requirements for a blade material in aircraft turbines operating at higher temperatures were compared with the actual performance as found in COTAC DS composite testing. The structure and properties of the more fully developed 74 and 741 types were specified. High temperature structural stability, impact of thermal and mechanical fatigue, oxidation resistance and coating capability were thoroughly evaluated. The problem of cooling passages in DS eutectic blades is also outlined.

Adsorption properties of BSA and DsRed proteins deposited on thin SiO2 layers: optically non-absorbing versus absorbing proteins

NASA Astrophysics Data System (ADS)

Scarangella, A.; Soumbo, M.; Villeneuve-Faure, C.; Mlayah, A.; Bonafos, C.; Monje, M.-C.; Roques, C.; Makasheva, K.

2018-03-01

Protein adsorption on solid surfaces is of interest for many industrial and biomedical applications, where it represents the conditioning step for micro-organism adhesion and biofilm formation. To understand the driving forces of such an interaction we focus in this paper on the investigation of the adsorption of bovine serum albumin (BSA) (optically non-absorbing, model protein) and DsRed (optically absorbing, naturally fluorescent protein) on silica surfaces. Specifically, we propose synthesis of thin protein layers by means of dip coating of the dielectric surface in protein solutions with different concentrations (0.01-5.0 g l-1). We employed spectroscopic ellipsometry as the most suitable and non-destructive technique for evaluation of the protein layers’ thickness and optical properties (refractive index and extinction coefficient) after dehydration, using two different optical models, Cauchy for BSA and Lorentz for DsRed. We demonstrate that the thickness, the optical properties and the wettability of the thin protein layers can be finely controlled by proper tuning of the protein concentration in the solution. These results are correlated with the thin layer morphology, investigated by AFM, FTIR and PL analyses. It is shown that the proteins do not undergo denaturation after dehydration on the silica surface. The proteins arrange themselves in a lace-like network for BSA and in a rod-like structure for DsRed to form mono- and multi-layers, due to different mechanisms driving the organization stage.

Source characteristics of the 2015 MW 7.8 Gorkha (Nepal) earthquake and its MW 7.2 aftershock from space geodesy

NASA Astrophysics Data System (ADS)

Feng, Wanpeng; Lindsey, Eric; Barbot, Sylvain; Samsonov, Sergey; Dai, Keren; Li, Peng; Li, Zhenhong; Almeida, Rafael; Chen, Jiajun; Xu, Xiaohua

2017-08-01

On April 25, 2015, a destructive MW 7.8 earthquake struck the capital of Nepal, Kathmandu, killing more than 8800 people and destroying numerous historical structures. We analyze six coseismic interferograms from several satellites (ALOS-2, Sentinel-1 A, and RADARSAT-2), as well as three-dimensional displacements at six GPS stations to investigate fault structure and slip distribution of the Gorkha earthquake. Using a layered crustal structure, the best-fit slip model shows that the preferred dip angle of the mainshock fault is 6 ± 3.5° and the major slip is concentrated within depths of 8-15 km. The maximum slip of 6.0 m occurs at a depth of 11 km, 70 km south east of the epicenter. The coseismic rupture extends 150 km eastward of the epicentre with a cumulative geodetic moment of 7.8 × 1020 Nm, equivalent to an earthquake of MW 7.84. We also investigate the MW 7.2 aftershock on 12 May 2015 using another three postseismic interferograms from ALOS2, RADARSAT-2, and Sentinel-1 A. The InSAR-based best-fit slip model of the largest aftershock implies that its major slip is next to the eastern lower end of the mainshock rupture with a similar maximum slip of 6 m at a depth of 13 km. This study generates various coseismic geodetic measurements to determine the source parameters of the MW 7.8 Gorkha earthquake and 12 May MW 7.2 afershock, providing an additional chance to understand the local fault structure and slip extent.

Development of a 5 MW reference gearbox for offshore wind turbines: 5 MW reference gearbox

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

Nejad, Amir Rasekhi; Guo, Yi; Gao, Zhen

2015-07-27

This paper presents detailed descriptions, modeling parameters and technical data of a 5MW high-speed gearbox developed for the National Renewable Energy Laboratory offshore 5MW baseline wind turbine. The main aim of this paper is to support the concept studies and research for large offshore wind turbines by providing a baseline gearbox model with detailed modeling parameters. This baseline gearbox follows the most conventional design types of those used in wind turbines. It is based on the four-point supports: two main bearings and two torque arms. The gearbox consists of three stages: two planetary and one parallel stage gears. The gearmore » ratios among the stages are calculated in a way to obtain the minimum gearbox weight. The gearbox components are designed and selected based on the offshore wind turbine design codes and validated by comparison to the data available from large offshore wind turbine prototypes. All parameters required to establish the dynamic model of the gearbox are then provided. Moreover, a maintenance map indicating components with high to low probability of failure is shown. The 5 MW reference gearbox can be used as a baseline for research on wind turbine gearboxes and comparison studies. It can also be employed in global analysis tools to represent a more realistic model of a gearbox in a coupled analysis.« less

Integrating the 3Ds: a nursing perspective.

PubMed

Villarruel, Antonia M; Bigelow, April; Alvarez, Carmen

2014-01-01

The 3Ds (diversity, disparities, and determinants) that serve as a framework for this supplement are concepts that are key foundations of nursing education, practice, and research. Despite this fact, however, the nursing profession has faced challenges recognizing the full potential of these concepts. While their importance is documented and acknowledged, they are not clearly evident or easily recognized within the nursing profession. In fact, there are many barriers to the integration of these concepts. We identify and address two barriers to addressing health disparities and increasing diversity: disconnects and discrimination. Furthermore, we discuss three factors-dissemination, durability, and data-that may facilitate nursing's efforts to integrate the 3Ds into the profession. Five pivotal models that address these barriers and facilitators are presented as exemplars that have the potential to guide efforts to address diversity, disparities, and social determinants of health and act as catalysts for change within the nursing profession.

Integrating the 3Ds: A Nursing Perspective

PubMed Central

Bigelow, April; Alvarez, Carmen

2014-01-01

The 3Ds (diversity, disparities, and determinants) that serve as a framework for this supplement are concepts that are key foundations of nursing education, practice, and research. Despite this fact, however, the nursing profession has faced challenges recognizing the full potential of these concepts. While their importance is documented and acknowledged, they are not clearly evident or easily recognized within the nursing profession. In fact, there are many barriers to the integration of these concepts. We identify and address two barriers to addressing health disparities and increasing diversity: disconnects and discrimination. Furthermore, we discuss three factors—dissemination, durability, and data—that may facilitate nursing's efforts to integrate the 3Ds into the profession. Five pivotal models that address these barriers and facilitators are presented as exemplars that have the potential to guide efforts to address diversity, disparities, and social determinants of health and act as catalysts for change within the nursing profession. PMID:24385663

Component Identification in Multi-Chemical Mixtures With Swept-Wavelength Resonant-Raman Spectroscopy

DTIC Science & Technology

2011-03-18

efficiency of the OPO, but ranges from up to 15 mW on target in the UV to 50 mW in the visible. This ability to illuminate a target with a broad...been back illuminated and coated for enhanced UV response. The run file which automates the collection process uses several input parameters to...analyzed by a Agilent spectrophotometer to determine absorbance characteristics of the liquid. The remaining mixture was then placed into a standard UV

Recognition of a 30,000 MW antigen of Giardia muris trophozoites by intestinal IgA from Giardia-infected mice.

PubMed

Heyworth, M F; Pappo, J

1990-08-01

The principal aims of this work were (i) to identify the molecular weight (MW) of Giardia muris trophozoite antigens that are recognized by IgA in small intestinal secretions from G. muris-infected mice, and (ii) to determine whether mouse intestinal Giardia-specific IgA is directed against trophozoite surfaces. BALB/c mice were infected with G. muris cysts, and intestinal secretions were harvested from these mice at various times after the start of Giardia infection, and from uninfected mice. Flow cytometry showed that intestinal IgA from G. muris-infected mice, but not from uninfected mice, became bound to trophozoite surfaces in vitro. Western blotting of trophozoite proteins with mouse intestinal secretions showed that IgA from Giardia-infected mice reacted specifically with a broad protein band of approximately 30,000 MW. This finding suggests that one or more trophozoite proteins of approximately 30,000 MW are targets for intestinal antibody in mice infected with G. muris.

Recognition of a 30,000 MW antigen of Giardia muris trophozoites by intestinal IgA from Giardia-infected mice.

PubMed Central

Heyworth, M F; Pappo, J

1990-01-01

The principal aims of this work were (i) to identify the molecular weight (MW) of Giardia muris trophozoite antigens that are recognized by IgA in small intestinal secretions from G. muris-infected mice, and (ii) to determine whether mouse intestinal Giardia-specific IgA is directed against trophozoite surfaces. BALB/c mice were infected with G. muris cysts, and intestinal secretions were harvested from these mice at various times after the start of Giardia infection, and from uninfected mice. Flow cytometry showed that intestinal IgA from G. muris-infected mice, but not from uninfected mice, became bound to trophozoite surfaces in vitro. Western blotting of trophozoite proteins with mouse intestinal secretions showed that IgA from Giardia-infected mice reacted specifically with a broad protein band of approximately 30,000 MW. This finding suggests that one or more trophozoite proteins of approximately 30,000 MW are targets for intestinal antibody in mice infected with G. muris. Images Figure 4 PMID:2394467

An Updated Catalog of Taiwan Earthquakes (1900-2011) with Homogenized Mw Magnitudes

NASA Astrophysics Data System (ADS)

Chen, K.; Tsai, Y.; Chang, W.

2012-12-01

A complete and consistent catalog of earthquakes can provide good data for studying the distribution of earthquakes in a region as function of space, time and magnitude. Therefore, it is a basic tool for studying seismic hazard and mitigating hazard, and we can get the seismicity with magnitude equal to or greater than Mw from the data set. In the article for completeness and consistence, we apply a catalog of earthquakes from 1900 to 2006 with homogenized magnitude (Mw) (Chen and Tsai, 2008) as a base, and we also refer to the Hsu (1989) to incorporate available supplementary data (total 188 data) for the period 1900-1935, the supplementary data lead the cutoff threshold magnitude to be from Mw 5.5 down to 5.0, this indicates that we add the additional data has enriched the magnitude > 5.0 content. For this study, the catalog has been updated to include earthquakes up to 2011, and it is complete for Mw > 5.0, this will increase the reliability for studying seismic hazard. It is found that it is saturated for original catalog of Taiwan earthquakes compared with Harvard Mw or USGS M for magnitude > 6.5. Although, we modified the original catalog into seismic moment magnitude Mw, it still does not overcome the drawback. But, it is found for Mw < 6.5, our unified Mw are most greater than Harvard Mw or USGS M, the phenomenon indicates our unified Mw to supplement the gap above magnitude > 6.0 and somewhere magnitude > 5.5 during the time period 1973-1991 for original catalog. Therefore, it is better with Mw to report the earthquake magnitude.

Convective Heating of the LIFE Engine Target During Injection

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

Holdener, D S; Tillack, M S; Wang, X R

2011-10-24

Target survival in the hostile, high temperature xenon environment of the proposed Laser Inertial Fusion Energy (LIFE) engine is critical. This work focuses on the flow properties and convective heat load imposed upon the surface of the indirect drive target while traveling through the xenon gas. While this rarefied flow is traditionally characterized as being within the continuum regime, it is approaching transition where conventional CFD codes reach their bounds of operation. Thus ANSYS, specifically the Navier-Stokes module CFX, will be used in parallel with direct simulation Monte Carlo code DS2V and analytically and empirically derived expressions for heat transfermore » to the hohlraum for validation. Comparison of the viscous and thermal boundary layers of ANSYS and DS2V were shown to be nearly identical, with the surface heat flux varying less than 8% on average. From the results herein, external baffles have been shown to reduce this heat transfer to the sensitive laser entrance hole (LEH) windows and optimize target survival independent of other reactor parameters.« less

The myeloid-binding peptide adenoviral vector enables multi-organ vascular endothelial gene targeting.

PubMed

Lu, Zhi Hong; Kaliberov, Sergey; Zhang, Jingzhu; Muz, Barbara; Azab, Abdel K; Sohn, Rebecca E; Kaliberova, Lyudmila; Du, Yingqiu; Curiel, David T; Arbeit, Jeffrey M

2014-08-01

Vascular endothelial cells (ECs) are ideal gene therapy targets as they provide widespread tissue access and are the first contact surfaces following intravenous vector administration. Human recombinant adenovirus serotype 5 (Ad5) is the most frequently used gene transfer system because of its appreciable transgene payload capacity and lack of somatic mutation risk. However, standard Ad5 vectors predominantly transduce liver but not the vasculature following intravenous administration. We recently developed an Ad5 vector with a myeloid cell-binding peptide (MBP) incorporated into the knob-deleted, T4 fibritin chimeric fiber (Ad.MBP). This vector was shown to transduce pulmonary ECs presumably via a vector handoff mechanism. Here we tested the body-wide tropism of the Ad.MBP vector, its myeloid cell necessity, and vector-EC expression dose response. Using comprehensive multi-organ co-immunofluorescence analysis, we discovered that Ad.MBP produced widespread EC transduction in the lung, heart, kidney, skeletal muscle, pancreas, small bowel, and brain. Surprisingly, Ad.MBP retained hepatocyte tropism albeit at a reduced frequency compared with the standard Ad5. While binding specifically to myeloid cells ex vivo, multi-organ Ad.MBP expression was not dependent on circulating monocytes or macrophages. Ad.MBP dose de-escalation maintained full lung-targeting capacity but drastically reduced transgene expression in other organs. Swapping the EC-specific ROBO4 for the CMV promoter/enhancer abrogated hepatocyte expression but also reduced gene expression in other organs. Collectively, our multilevel targeting strategy could enable therapeutic biological production in previously inaccessible organs that pertain to the most debilitating or lethal human diseases.

Magnetic Multi-Scale Mapping to Characterize Anthropogenic Targets

NASA Astrophysics Data System (ADS)

Le Maire, P.; Munschy, M.

2017-12-01

The discovery of buried anthropic objects on construction sites can cause delays and/or dangers for workers and for the public. Indeed, every year 500 tons of Unexploded-ordnance are discovered in France. Magnetic measurements are useful to localize magnetized objects. Moreover, it is the cheapest geophysical method which does not impact environment and which is relatively fast to perform. Fluxgate magnetometers (three components) are used to measure magnetic properties bellow the ground. These magnetic sensors are not absolute, so they need to be calibrated before the onset of the measurements. The advantage is that they allow magnetic compensation of the equipment attached to the sensor. So the choice of this kind sensor gives the opportunity to install the equipment aboard different magnetized supports: boat, quad bike, unmanned aerial vehicle, aircraft,... Indeed, this methodology permits to perform magnetic mapping with different scale and different elevation above ground level. An old French aerial military plant was chosen to perform this multi-scale approach. The advantage of the site is that it contains a lot of different targets with variable sizes and depth, e.g. buildings, unexploded-ordnances of the two world wars, trenches, pipes,… By comparison between the different magnetic anomaly maps at different elevations some of the geometric parameters of the magnetic sources can be characterized. The comparison between measured maps at different elevations and the prolonged map highlights the maximum distance for the target's detection (figure).

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

3rd-generation MW/LWIR sensor engine for advanced tactical systems

NASA Astrophysics Data System (ADS)

King, Donald F.; Graham, Jason S.; Kennedy, Adam M.; Mullins, Richard N.; McQuitty, Jeffrey C.; Radford, William A.; Kostrzewa, Thomas J.; Patten, Elizabeth A.; McEwan, Thomas F.; Vodicka, James G.; Wootan, John J.

2008-04-01

Raytheon has developed a 3rd-Generation FLIR Sensor Engine (3GFSE) for advanced U.S. Army systems. The sensor engine is based around a compact, productized detector-dewar assembly incorporating a 640 x 480 staring dual-band (MW/LWIR) focal plane array (FPA) and a dual-aperture coldshield mechanism. The capability to switch the coldshield aperture and operate at either of two widely-varying f/#s will enable future multi-mode tactical systems to more fully exploit the many operational advantages offered by dual-band FPAs. RVS has previously demonstrated high-performance dual-band MW/LWIR FPAs in 640 x 480 and 1280 x 720 formats with 20 μm pitch. The 3GFSE includes compact electronics that operate the dual-band FPA and variable-aperture mechanism, and perform 14-bit analog-to-digital conversion of the FPA output video. Digital signal processing electronics perform "fixed" two-point non-uniformity correction (NUC) of the video from both bands and optional dynamic scene-based NUC; advanced enhancement processing of the output video is also supported. The dewar-electronics assembly measures approximately 4.75 x 2.25 x 1.75 inches. A compact, high-performance linear cooler and cooler electronics module provide the necessary FPA cooling over a military environmental temperature range. 3GFSE units are currently being assembled and integrated at RVS, with the first units planned for delivery to the US Army.

2μm all fiber multi-wavelength Tm/Ho co-doped fiber laser

NASA Astrophysics Data System (ADS)

Zhang, Junhong; Jiang, Qiuxia; Wang, Xiaofa

2017-10-01

A 2 μm all fiber multi-wavelength Tm/Ho co-doped fiber laser based on a simple ring cavity is experimentally demonstrated. Compared with other 2 μm multi-wavelength Tm/Ho co-doped fiber lasers, the multi-wavelength fiber laser is obtained by the gain saturation effect and inhomogeneous broadening effect without any frequency selector component, filter component or polarization-dependent component. When the pump power is about 304 mW, the fiber laser enters into single-wavelength working state around 1967.76 nm. Further increasing the pump power to 455 mW, a stable dual-wavelength laser is obtained at room temperature. The bimodal power difference between λ1 and λ2 is 5.528 dB. The fluctuations of wavelength and power are less than 0.03 nm and 0.264 dB in an hour, which demonstrates that the multi-wavelength fiber laser works at a stable state. Furthermore, a research about the relationship between the pump power and the output spectra has been made.

Lipopolysaccharide-binding alkylpolyamine DS-96 inhibits Chlamydia trachomatis infection by blocking attachment and entry.

PubMed

Osaka, Ichie; Hefty, P Scott

2014-06-01

Vaginally delivered microbicides are being developed to offer women self-initiated protection against transmission of sexually transmitted infections such as Chlamydia trachomatis. A small molecule, DS-96, rationally designed for high affinity to Escherichia coli lipid A, was previously demonstrated to bind and neutralize lipopolysaccharide (LPS) from a wide variety of Gram-negative bacteria (D. Sil et al., Antimicrob. Agents Chemother. 51: 2811-2819, 2007, doi:10.1128/AAC.00200-07). Aside from the lack of the repeating O antigen, chlamydial lipooligosaccharide (LOS) shares general molecular architecture features with E. coli LPS. Importantly, the portion of lipid A where the interaction with DS-96 is expected to take place is well conserved between the two organisms, leading to the hypothesis that DS-96 inhibits Chlamydia infection by binding to LOS and compromising the function. In this study, antichlamydial activity of DS-96 was examined in cell culture. DS-96 inhibited the intercellular growth of Chlamydia in a dose-dependent manner and offered a high level of inhibition at a relatively low concentration (8 μM). The data also revealed that infectious elementary bodies (EBs) were predominantly blocked at the attachment step, as indicated by the reduced number of EBs associated with the host cell surface following pretreatment. Of those EBs that were capable of attachment, the vast majority was unable to gain entry into the host cell. Inhibition of EB attachment and entry by DS-96 suggests that Chlamydia LOS is critical to these processes during the developmental cycle. Importantly, given the low association of host toxicity previously reported by Sil et al., DS-96 is expected to perform well in animal studies as an active antichlamydial compound in a vaginal microbicide. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Concentrating Solar Power Projects - Gansu Akesai 50MW Molten Salt Trough

Science.gov Websites

project | Concentrating Solar Power | NREL Gansu Akesai 50MW Molten Salt Trough project Status . Technology: Parabolic trough Turbine Capacity: Net: 50.0 MW Gross: 50.0 MW Status: Under development Do you have more information, corrections, or comments? Background Technology: Parabolic trough Status: Under

48 CFR 9903.202-10 - Illustration of Disclosure Statement Form, CASB DS-2.

Code of Federal Regulations, 2012 CFR

2012-10-01

... of Disclosure Statement Form, CASB DS-2. The data which are required to be disclosed by educational institutions are set forth in detail in the Disclosure Statement Form, CASB DS-2, which is illustrated below... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Illustration of Disclosure...

48 CFR 9903.202-10 - Illustration of Disclosure Statement Form, CASB DS-2.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of Disclosure Statement Form, CASB DS-2. The data which are required to be disclosed by educational institutions are set forth in detail in the Disclosure Statement Form, CASB DS-2, which is illustrated below... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Illustration of Disclosure...

Infrared and visible image fusion with the target marked based on multi-resolution visual attention mechanisms

NASA Astrophysics Data System (ADS)

Huang, Yadong; Gao, Kun; Gong, Chen; Han, Lu; Guo, Yue

2016-03-01

During traditional multi-resolution infrared and visible image fusion processing, the low contrast ratio target may be weakened and become inconspicuous because of the opposite DN values in the source images. So a novel target pseudo-color enhanced image fusion algorithm based on the modified attention model and fast discrete curvelet transformation is proposed. The interesting target regions are extracted from source images by introducing the motion features gained from the modified attention model, and source images are performed the gray fusion via the rules based on physical characteristics of sensors in curvelet domain. The final fusion image is obtained by mapping extracted targets into the gray result with the proper pseudo-color instead. The experiments show that the algorithm can highlight dim targets effectively and improve SNR of fusion image.

Concentrating Solar Power Projects - Shangyi 50MW DSG Tower CSP project |

Science.gov Websites

Concentrating Solar Power | NREL Shangyi 50MW DSG Tower CSP project Status Date: September 27 : 50.0 MW Gross: 50.0 MW Status: Under development Do you have more information, corrections, or comments ? Background Technology: Power tower Status: Under development Country: China City: Shangyi Region: Hebei

Concentrating Solar Power Projects - Yumen 100MW Molten Salt Tower CSP

Science.gov Websites

project | Concentrating Solar Power | NREL 100MW Molten Salt Tower CSP project Status Date Turbine Capacity: Net: 100.0 MW Gross: 100.0 MW Status: Under development Do you have more information , corrections, or comments? Background Technology: Power tower Status: Under development Country: China City

Multi-Mode, Multi-Antenna Software Defined Radar for Adaptive Tracking and Identification of Targets in Urban Environments

DTIC Science & Technology

2011-10-31

designs with code division multiple access ( CDMA ). Analog chirp filters were used to produce an up-chirp, which is used as a radar waveform, coupled with...signals. A potential shortcoming of CDMA techniques is that the addition of two signals will result in a non-constant amplitude signal which will be...of low-frequency A/ Ds . As an example for a multiple carrier signal all the received signals from the multiple carriers are aliased onto the

An anti-DNA antibody prefers damaged dsDNA over native.

PubMed

Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

2017-01-01

DNA-protein interactions, including DNA-antibody complexes, have both fundamental and practical significance. In particular, antibodies against double-stranded DNA play an important role in the pathogenesis of autoimmune diseases. Elucidation of structural mechanisms of an antigen recognition and interaction of anti-DNA antibodies provides a basis for understanding the role of DNA-containing immune complexes in human pathologies and for new treatments. Here we used Molecular Dynamic simulations of bimolecular complexes of a segment of dsDNA with a monoclonal anti-DNA antibody's Fab-fragment to obtain detailed structural and physical characteristics of the dynamic intermolecular interactions. Using a computationally modified crystal structure of a Fab-DNA complex (PDB: 3VW3), we studied in silico equilibrium Molecular Dynamics of the Fab-fragment associated with two homologous dsDNA fragments, containing or not containing dimerized thymine, a product of DNA photodamage. The Fab-fragment interactions with the thymine dimer-containing DNA was thermodynamically more stable than with the native DNA. The amino acid residues constituting a paratope and the complementary nucleotide epitopes for both Fab-DNA constructs were identified. Stacking and electrostatic interactions were shown to play the main role in the antibody-dsDNA contacts, while hydrogen bonds were less significant. The aggregate of data show that the chemically modified dsDNA (containing a covalent thymine dimer) has a higher affinity toward the antibody and forms a stronger immune complex. These findings provide a mechanistic insight into formation and properties of the pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus, associated with skin photosensibilization and DNA photodamage.

Measurement of B_{s}^{0} and D_{s}^{-} Meson Lifetimes.

PubMed

Aaij, R; Adeva, B; Adinolfi, M; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Archilli, F; d'Argent, P; Arnau Romeu, J; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Babuschkin, I; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baker, S; Balagura, V; Baldini, W; Baranov, A; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Baryshnikov, F; Baszczyk, M; Batozskaya, V; Batsukh, B; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Beiter, A; Bel, L J; Bellee, V; Belloli, N; Belous, K; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Beranek, S; Berezhnoy, A; Bernet, R; Bertolin, A; Betancourt, C; Betti, F; Bettler, M-O; van Beuzekom, M; Bezshyiko, Ia; Bifani, S; Billoir, P; Birnkraut, A; Bitadze, A; Bizzeti, A; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Boettcher, T; Bondar, A; Bondar, N; Bonivento, W; Bordyuzhin, I; Borgheresi, A; Borghi, S; Borisyak, M; Borsato, M; Bossu, F; Boubdir, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britton, T; Brodzicka, J; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Campora Perez, D H; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cavallero, G; Cenci, R; Chamont, D; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S-F; Chobanova, V; Chrzaszcz, M; Chubykin, A; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombs, G; Coquereau, S; Corti, G; Corvo, M; Costa Sobral, C M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Da Cunha Marinho, F; Dall'Occo, E; Dalseno, J; David, P N Y; Davis, A; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Serio, M; De Simone, P; Dean, C T; Decamp, D; Deckenhoff, M; Del Buono, L; Dembinski, H-P; Demmer, M; Dendek, A; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Nezza, P; Dijkstra, H; Dordei, F; Dorigo, M; Dosil Suárez, A; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Dungs, K; Durante, P; Dzhelyadin, R; Dziewiecki, M; Dziurda, A; Dzyuba, A; Déléage, N; Easo, S; Ebert, M; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Farley, N; Farry, S; Fay, R; Fazzini, D; Ferguson, D; Fernandez, G; Fernandez Prieto, A; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fini, R A; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Franco Lima, V; Frank, M; Frei, C; Fu, J; Funk, W; Furfaro, E; Färber, C; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; Garcia Martin, L M; García Pardiñas, J; Garra Tico, J; Garrido, L; Garsed, P J; Gascon, D; Gaspar, C; Gavardi, L; Gazzoni, G; Gerick, D; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gianì, S; Gibson, V; Girard, O G; Giubega, L; Gizdov, K; Gligorov, V V; Golubkov, D; Golutvin, A; Gomes, A; Gorelov, I V; Gotti, C; Govorkova, E; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graverini, E; Graziani, G; Grecu, A; Greim, R; Griffith, P; Grillo, L; Gruberg Cazon, B R; Grünberg, O; Gushchin, E; Guz, Yu; Gys, T; Göbel, C; Hadavizadeh, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hamilton, B; Han, X; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hatch, M; He, J; Head, T; Heister, A; Hennessy, K; Henrard, P; Henry, L; van Herwijnen, E; Heß, M; Hicheur, A; Hill, D; Hombach, C; Hopchev, H; Huard, Z-C; Hulsbergen, W; Humair, T; Hushchyn, M; Hutchcroft, D; Idzik, M; Ilten, P; Jacobsson, R; Jalocha, J; Jans, E; Jawahery, A; Jiang, F; John, M; Johnson, D; Jones, C R; Joram, C; Jost, B; Jurik, N; Kandybei, S; Karacson, M; Kariuki, J M; Karodia, S; Kecke, M; Kelsey, M; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Klimkovich, T; Koliiev, S; Kolpin, M; Komarov, I; Kopecna, R; Koppenburg, P; Kosmyntseva, A; Kotriakhova, S; Kozachuk, A; Kozeiha, M; Kravchuk, L; Kreps, M; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kurek, K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Leflat, A; Lefrançois, J; Lefèvre, R; Lemaitre, F; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, T; Li, Y; Li, Z; Likhomanenko, T; Lindner, R; Lionetto, F; Liu, X; Loh, D; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusiani, A; Lyu, X; Machefert, F; Maciuc, F; Maev, O; Maguire, K; Malde, S; Malinin, A; Maltsev, T; Manca, G; Mancinelli, G; Manning, P; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marinangeli, M; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurice, E; Maurin, B; Mazurov, A; McCann, M; McNab, A; McNulty, R; Meadows, B; Meier, F; Melnychuk, D; Merk, M; Merli, A; Michielin, E; Milanes, D A; Minard, M-N; Mitzel, D S; Mogini, A; Molina Rodriguez, J; Monroy, I A; Monteil, S; Morandin, M; Morello, M J; Morgunova, O; Moron, J; Morris, A B; Mountain, R; Muheim, F; Mulder, M; Mussini, M; Müller, D; Müller, J; Müller, K; Müller, V; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, T D; Nguyen-Mau, C; Nieswand, S; Niet, R; Nikitin, N; Nikodem, T; Nogay, A; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Oldeman, R; Onderwater, C J G; Ossowska, A; Otalora Goicochea, J M; Owen, P; Oyanguren, A; Pais, P R; Palano, A; Palutan, M; Papanestis, A; Pappagallo, M; Pappalardo, L L; Pappenheimer, C; Parker, W; Parkes, C; Passaleva, G; Pastore, A; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petrov, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Placinta, V; Playfer, S; Plo Casasus, M; Poikela, T; Polci, F; Poli Lener, M; Poluektov, A; Polyakov, I; Polycarpo, E; Pomery, G J; Ponce, S; Popov, A; Popov, D; Popovici, B; Poslavskii, S; Potterat, C; Price, E; Prisciandaro, J; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, C; Qian, W; Quagliani, R; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Ratnikov, F; Raven, G; Redi, F; Reichert, S; Dos Reis, A C; Remon Alepuz, C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Rogozhnikov, A; Roiser, S; Rollings, A; Romanovskiy, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Rudolph, M S; Ruf, T; Ruiz Valls, P; Saborido Silva, J J; Sadykhov, E; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Gonzalo, D; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schellenberg, M; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schreiner, H F; Schubert, K; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Sergi, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Simone, S; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, I T; Smith, J; Smith, M; Soares Lavra, L; Sokoloff, M D; Soler, F J P; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefko, P; Stefkova, S; Steinkamp, O; Stemmle, S; Stenyakin, O; Stevens, H; Stoica, S; Stone, S; Storaci, B; Stracka, S; Stramaglia, M E; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Syropoulos, V; Szczekowski, M; Szumlak, T; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, E; van Tilburg, J; Tilley, M J; Tisserand, V; Tobin, M; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Toriello, F; Tourinho Jadallah Aoude, R; Tournefier, E; Tourneur, S; Trabelsi, K; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tully, A; Tuning, N; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valassi, A; Valat, S; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Venkateswaran, A; Verlage, T A; Vernet, M; Vesterinen, M; Viana Barbosa, J V; Viaud, B; Vieira, D; Vieites Diaz, M; Viemann, H; Vilasis-Cardona, X; Vitti, M; Volkov, V; Vollhardt, A; Voneki, B; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Vázquez Sierra, C; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Wark, H M; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Winn, M A; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wyllie, K; Xie, Y; Xing, Z; Xu, Z; Yang, Z; Yang, Z; Yao, Y; Yin, H; Yu, J; Yuan, X; Yushchenko, O; Zarebski, K A; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zheng, Y; Zhu, X; Zhukov, V; Zucchelli, S

2017-09-08

We report on a measurement of the flavor-specific B_{s}^{0} lifetime and of the D_{s}^{-} lifetime using proton-proton collisions at center-of-mass energies of 7 and 8 TeV, collected by the LHCb experiment and corresponding to 3.0  fb^{-1} of integrated luminosity. Approximately 407 000 B_{s}^{0}→D_{s}^{(*)-}μ^{+}ν_{μ} decays are partially reconstructed in the K^{+}K^{-}π^{-}μ^{+} final state. The B_{s}^{0} and D_{s}^{-} natural widths are determined using, as a reference, kinematically similar B^{0}→D^{(*)-}μ^{+}ν_{μ} decays reconstructed in the same final state. The resulting differences between widths of B_{s}^{0} and B^{0} mesons and of D_{s}^{-} and D^{-} mesons are Δ_{Γ}(B)=-0.0115±0.0053(stat)±0.0041(syst)  ps^{-1} and Δ_{Γ}(D)=1.0131±0.0117(stat)±0.0065(syst)  ps^{-1}, respectively. Combined with the known B^{0} and D^{-} lifetimes, these yield the flavor-specific B_{s}^{0} lifetime, τ_{B_{s}^{0}}^{fs}=1.547±0.013(stat)±0.010(syst)±0.004(τ_{B})  ps and the D_{s}^{-} lifetime, τ_{D_{s}^{-}}=0.5064±0.0030(stat)±0.0017(syst)±0.0017(τ_{D})  ps. The last uncertainties originate from the limited knowledge of the B^{0} and D^{-} lifetimes. The results improve upon current determinations.

The Folding of de Novo Designed Protein DS119 via Molecular Dynamics Simulations.

PubMed

Wang, Moye; Hu, Jie; Zhang, Zhuqing

2016-04-26

As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD) simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD) simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5-10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design.

Endothelial Targeting of Semi-permeable Polymer Nanocarriers for Enzyme Therapies

PubMed Central

Dziubla, Thomas D; Shuvaev, Vladimir V.; Hong, Nan Kang; Hawkins, Brian; Muniswamy, Madesh; Takano, Hajime; Simone, Eric; Nakada, Marian T.; Fisher, Aron; Albelda, Steven M.; Muzykantov, Vladimir R.

2007-01-01

The medical utility of proteins, e.g. therapeutic enzymes, is greatly restricted by their liable nature and inadequate delivery. Most therapeutic enzymes do not accumulate in their targets and are inactivated by proteases. Targeting of enzymes encapsulated into substrate-permeable Polymeric Nano-Carriers (PNC) impermeable for proteases might overcome these limitations. To test this hypothesis, we designed endothelial targeted PNC loaded with catalase, the H2O2-detoxifying enzyme, and tested if this approach protects against vascular oxidative stress, a pathological process implicated in ischemia-reperfusion and other disease conditions. Encapsulation of catalase (MW 240KD), peroxidase (MW 42kD) and xanthine oxidase (XO, MW 300 kD) into ~300nm diameter PNC composed of co-polymers of PEG-PLGA (polyethylene glycol and poly-lactic/poly-glycolic acid) was in the range ~10% for all enzymes. PNC/catalase and PNC/peroxidase were protected from external proteolysis and exerted the enzymatic activity on their PNC diffusible substrates, H2O2 and ortho-phenylendiamine, whereas activity of encapsulated XO was negligible due to polymer impermeability to the substrate. PNC targeted to platelet-endothelial cell adhesion molecule-1 delivered active encapsulated catalase to endothelial cells and protected the endothelium against oxidative stress in cell culture and animal studies. Vascular targeting of PNC-loaded detoxifying enzymes may find wide medical applications including management of oxidative stress and other toxicities. PMID:17950837

Concentrating Solar Power Projects - SunCan Dunhuang 100 MW Phase II |

Science.gov Websites

Concentrating Solar Power | NREL 0 MW Phase II Status Date: January 11, 2017 Project Overview ): Beijing Shouhang IHW Technology: Power tower Turbine Capacity: Net: 100.0 MW Gross: 100.0 MW Status: Under construction Do you have more information, corrections, or comments? Background Technology: Power tower Status

Concentrating Solar Power Projects - Yumen 50MW Thermal Oil Trough CSP

Science.gov Websites

project | Concentrating Solar Power | NREL Thermal Oil Trough CSP project Status Date : September 28, 2016 Project Overview Project Name: Yumen 50MW Thermal Oil Trough CSP project Country: China : Thermal Oil Power Block Turbine Capacity (Gross): 50.0 MW Turbine Capacity (Net): 50.0 MW Output Type

CADD Modeling of Multi-Target Drugs Against Alzheimer's Disease.

PubMed

Ambure, Pravin; Roy, Kunal

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder that is described by multiple factors linked with the progression of the disease. The currently approved drugs in the market are not capable of curing AD; instead, they merely provide symptomatic relief. Development of multi-target directed ligands (MTDLs) is an emerging strategy for improving the quality of the treatment against complex diseases like AD. Polypharmacology is a branch of pharmaceutical sciences that deals with the MTDL development. In this mini-review, we have summarized and discussed different strategies that are reported in the literature to design MTDLs for AD. Further, we have discussed the role of different in silico techniques and online resources in computer-aided drug discovery (CADD), for designing or identifying MTDLs against AD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

RNA-dependent RNA polymerases of dsRNA bacteriophages.

PubMed

Makeyev, Eugene V; Grimes, Jonathan M

2004-04-01

Genome replication and transcription of riboviruses are catalyzed by an RNA-dependent RNA polymerase (RdRP). RdRPs are normally associated with other virus- or/and host-encoded proteins that modulate RNA polymerization activity and template specificity. The polymerase complex of double-stranded dsRNA viruses is a large icosahedral particle (inner core) containing RdRP as a minor constituent. In phi6 and other dsRNA bacteriophages from the Cystoviridae family, the inner core is composed of four virus-specific proteins. Of these, protein P2, or Pol subunit, has been tentatively identified as RdRP by sequence comparisons, but the role of this protein in viral RNA synthesis has not been studied until recently. Here, we overview the work on the Pol subunits of phi6 and related viruses from the standpoints of function, structure and evolution.

Absolute measurement of hadronic branching fractions of the Ds+ meson.

PubMed

Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Mehrabyan, S; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Libby, J; Powell, A; Wilkinson, G; Ecklund, K M; Love, W; Savinov, V; Lopez, A; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Mountain, R; Nisar, S; Randrianarivony, K; Sultana, N; Skwarnicki, T; Stone, S; Wang, J C; Zhang, L M; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Rademacker, J; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L

2008-04-25

The branching fractions of D(s)(+/-) meson decays serve to normalize many measurements of processes involving charm quarks. Using 298 pb(-1) of e(+)e(-) collisions recorded at a center of mass energy of 4.17 GeV, we determine absolute branching fractions for eight D(s)(+/-) decays with a double tag technique. In particular we determine the branching fraction B(D(s)(+)-->K(-)K(+}pi(+))=(5.50+/-0.23+/-0.16)%, where the uncertainties are statistical and systematic, respectively. We also provide partial branching fractions for kinematic subsets of the K(-)K(+)pi(+) decay mode.

Subthreshold social cognitive deficits may be a key to distinguish 22q11.2DS from schizophrenia.

PubMed

Peyroux, Elodie; Rigard, Caroline; Saucourt, Guillaume; Poisson, Alice; Plasse, Julien; Franck, Nicolas; Demily, Caroline

2018-03-25

Social cognitive impairments are core features in 22q11.2 deletion syndrome (22q11.2DS) and schizophrenia (SCZ). Indeed, adults with 22q.11.2 DS often have poorer social competence as well as poorer performance on measures of social cognitive skills (emotion recognition and theory of mind, ToM) compared with typically developing people. However, studies comparing specific social cognitive components in 22q11.2DS and SCZ have not yet been widely conducted. In this study we compared performances of 22q11.2DS and SCZ on both facial emotion recognition and ToM. Patients with 22q11.2DS (n = 18) and matched SCZ patients were recruited. After neuropsychological testing, the facial emotion recognition test assessed the patients' ability to recognize six basic, universal emotions (joy, anger, sadness, fear, disgust, and contempt). The Versailles-situational intentional reading evaluated ToM with six scenes from movies showing characters in complex interactions (involving hints, lies, and indirect speech). We show that 22q11.2DS exhibited significantly lower performance in emotion recognition than SCZ patients did, especially for disgust, contempt, and fear. This impairment seems to be a core cognitive phenotype in 22q11.2DS, regardless of the presence of SCZ symptoms. Concerning ToM, our results may highlight the same impairment level in 22q11.2DS and SCZ but require to be replicated in a larger cohort. Our results document the existence of threshold social cognitive deficits distinguishing 22q11.2DS from SCZ. © 2018 John Wiley & Sons Australia, Ltd.

Design and Prototype Implementation of non-Triggered Database-driven Real-time Tsunami Forecast System using Multi-index Method

NASA Astrophysics Data System (ADS)

Yamamoto, N.; Aoi, S.; Suzuki, W.; Hirata, K.; Takahashi, N.; Kunugi, T.; Nakamura, H.

2016-12-01

We have launched a new project to develop real-time tsunami inundation forecast system for the Pacific coast of Chiba prefecture (Kujukuri-Sotobo region), Japan (Aoi et al., 2015, AGU). In this study, we design a database-driven real-time tsunami forecast system using the multi-index method (Yamamoto et al., 2016, EPS) and implement a prototype system. In the previous study (Yamamoto et al., 2015, AGU), we assumed that the origin-time of tsunami was known before a forecast based on comparing observed and calculated ocean-bottom pressure waveforms stored in the Tsunami Scenario Bank (TSB). As shown in the figure, we assume the scenario origin-times by defining the scenario elapsed timeτp to compare observed and calculated waveforms. In this design, when several appropriate tsunami scenarios were selected by multiple indices (two variance reductions and correlation coefficient), the system could make tsunami forecast using the selected tsunami scenarios for the target coastal region without any triggered information derived from observed seismic and/or tsunami data. In addition, we define the time range Tq shown in the figure for masking perturbations contaminated by ocean-acoustic and seismic waves on the observed pressure records (Saito, 2015, JpGU). Following the proposed design, we implement a prototype system of real-time tsunami inundation forecast system for the exclusive use of the target coastal region using ocean-bottom pressure data from the Seafloor Observation Network for Earthquakes and Tsunamis along the Japan Trench (S-net) (Kanazawa et al., 2012, JpGU; Uehira et al., 2015, IUGG), which is constructed by National Research institute for Earth Science and Disaster Resilience (NIED). For the prototype system, we construct a prototype TSB using interplate earthquake fault models located along the Japan Trench (Mw 7.6-9.8), the Sagami Trough (Mw 7.6-8.6), and the Nankai Trough (Mw 7.6-8.6) as well as intraplate earthquake fault models (Mw 7.6-8.6) within

Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.

PubMed

Tarkang, Protus Arrey; Appiah-Opong, Regina; Ofori, Michael F; Ayong, Lawrence S; Nyarko, Alexander K

2016-01-01

There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction.

PubMed

Oliveira, Rodrigo C; Oliveira, Isabela S; Santiago, Mittermayer B; Sousa Atta, Maria L B; Atta, Ajax M

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

The 140 GHZ, 1 MW Gyrotron - Status and Recent Results

NASA Astrophysics Data System (ADS)

Gantenbein, G.; Dammertz, G.; Illy, S.; Kern, S.; Leonhardt, W.; Piosczyk, B.; Schmid, M.; Thumm, M.; Braune, H.; Erckmann, V.; Laqua, H. P.; Michel, G.; Kasparek, W.; Lechte, C.; Legrand, F.; Lievin, C.; Prinz, O.

2009-04-01

A 10 MW ECRH system is currently under construction for the stellarator W7-X which will be built up and operated by IPP in Greifswald, Germany. The present status of the complete system is reported in [1]. The RF power will be provided by 10 gyrotrons. A European collaboration has been established to develop and build the 10 gyrotrons each with an output power of 1 MW for continuous wave (CW) operation [2]. Nine gyrotrons are being manufactured by Thales Electron Devices (TED), Vélizy, France, one gyrotron was produced by CPI, Palo Alto, CA and passed the acceptance tests at IPP. The acceptance tests of the TED gyrotrons are performed at the test stand at FZK and on site at IPP. The first series tube yielded a total output power of 0.98 MW, with an efficiency of 31 % (without a single stage depressed collector) in short pulse operation and of 0.92 MW in pulses of 1800 s (efficiency of almost 45 % at a depression voltage of 29 kV) [3], The Gaussian mode output power was 0.91 MW. The RF power, measured in a calorimetric load at the end of a 25 m long quasi-optical transmission line with seven mirrors, was 0.87 MW. In this contribution typical results of the next series gyrotrons will be reported.

Multi-ligand nanoparticles for targeted drug delivery to the injured vascular wall

NASA Astrophysics Data System (ADS)

Kona, Soujanya

Pathological conditions like coronary artery disease, acute myocardial infarction, stroke, and peripheral artery diseases as well as cardiovascular interventions used in the treatment of coronary artery diseases such as angioplasty and stenting damage/injure the blood vessel wall, leading to inflamed or activated endothelial cells that have been implicated in events leading to thrombosis, inflammation, and restenosis. Oral administration of anti-coagulant and anti-inflammatory drugs causes systemic toxicity, bleeding, patient incompliance, and inadequate amounts of drugs at the injured area. Though drug-eluting stents have shown therapeutic benefits, complications such as in-stent restenosis and late thrombosis still remain and are a cause for concern. Rapid growth in the field of nanotechnology and nanoscience in recent years has paved the way for new targeted and controlled drug delivery strategies. In this perspective, the development of biodegradable nanoparticles for targeted intracellular drug delivery to the inflamed endothelial cells may offer an improved avenue for treatment of cardiovascular diseases. The major objective of this research was to develop "novel multi-ligand nanoparticles," as drug carriers that can efficiently target and deliver therapeutic agents to the injured/inflamed vascular cells under dynamic flow conditions. Our approach mimics the natural binding ability of platelets to injured/activated endothelial cells through glycoprotein Ib (GPIb) bound to P-selectin expressed on inflamed endothelial cells and to the subendothelium through GPIb binding to von Willebrand factor (vWF) deposited onto the injured vascular wall. Our design also exploits the natural cell membrane translocation ability of the internalizing cell peptide - trans-activating transcriptor (TAT) to enhance the nanoparticle uptake by the targeted cells. Our hypothesis is that these multi-ligand nanoparticles would show an increased accumulation at the injury site since GPIb

Containers of DS-2 Decontaminating Solution

DTIC Science & Technology

1982-03-01

percent sodium hydroxide, and the remainder is ethylene glycol monomethyl ether. Because of its reactivity, it must be protected from moisture and... carbon dioxide. It has been demonstrated that DS-2 does not corrode terneplate or steel. However, satisfactory terneplate and steel containers are...not produce a pail with a polyethylene insert. However, Mr. Wood told me that Hedwin Corporation (a subsidiary of Solvay ) does produce this kind of

[Dobutamine stress magnetic resonance imaging (DS-MRI), a valuable tool for the diagnosis of ischemic heart disease].

PubMed

van Dijkman, P R M; Kuijpers, Th J A; Blom, B M; van Herpen, G

2002-07-13

Assessment of the clinical applicability of DS-MRI for the detection of myocardial ischemia and myocardial viability. Prospective. In the period from 1 November 1999 to 31 October 2000, patients with suspected coronary artery disease who could not be studied by means of conventional bicycle ergometry underwent breath-hold DS-MRI (1 Tesla) 4 days after cessation of anti-ischemic medication. Three left ventricular short-axis planes were examined for the occurrence of disorders in wall movement during infusion of increasing doses of dobutamine (10, 20, 30 and 40 micrograms/kg/min). Temporary recovery of wall thickening in a previously diminished or non-contracting segment under 5 micrograms/kg/min of dobutamine was considered proof of viability. Development of hypo-, a- or dyskinesia at higher doses of dobutamine was taken to indicate ischemia. If the DS-MRI test was positive for ischemia, coronary angiography was performed. If indicated, this was followed by revascularisation. If DS-MRI did not reveal ischemia, the patient was seen at the outpatient department. Of the 100 patients (62 men and 38 women with an average age of 62 years, SD = 12) subjected to DS-MRI, 95 yielded results that were suitable for diagnosis. Of the 42 patients with DS-MRI scans that were considered positive for ischemia and in whom coronary angiography was subsequently performed, 41 had such coronary abnormalities that revascularisation was indicated. One patient was false-positive. All 53 patients with non-ischemic DS-MRI scans were followed-up for 11-23 months (mean 17 months). One patient died suddenly 2 weeks after the MRI-test. The other 52 patients did not experience any coronary events nor sudden cardiac death. The predictive value of a positive DS-MRI scan for ischemia was 98% and the predictive value of a negative DS-MRI scan was also 98%. DS-MRI is a safe diagnostic method for the detection or exclusion of myocardial ischemia and viability in patients with suspected coronary artery

Protein chainmail variants in dsDNA viruses

PubMed Central

Zhou, Z. Hong; Chiou, Joshua

2017-01-01

First discovered in bacteriophage HK97, biological chainmail is a highly stable system formed by concatenated protein rings. Each subunit of the ring contains the HK97-like fold, which is characterized by its submarine-like shape with a 5-stranded β sheet in the axial (A) domain, spine helix in the peripheral (P) domain, and an extended (E) loop. HK97 capsid consists of covalently-linked copies of just one HK97-like fold protein and represents the most effective strategy to form highly stable chainmail needed for dsDNA genome encapsidation. Recently, near-atomic resolution structures enabled by cryo electron microscopy (cryoEM) have revealed a range of other, more complex variants of this strategy for constructing dsDNA viruses. The first strategy, exemplified by P22-like phages, is the attachment of an insertional (I) domain to the core 5-stranded β sheet of the HK97-like fold. The atomic models of the Bordetella phage BPP-1 showcases an alternative topology of the classic HK97 topology of the HK97-like fold, as well as the second strategy for constructing stable capsids, where an auxiliary jellyroll protein dimer serves to cement the non-covalent chainmail formed by capsid protein subunits. The third strategy, found in lambda-like phages, uses auxiliary protein trimers to stabilize the underlying non-covalent chainmail near the 3-fold axis. Herpesviruses represent highly complex viruses that use a combination of these strategies, resulting in four-level hierarchical organization including a non-covalent chainmail formed by the HK97-like fold domain found in the floor region. A thorough understanding of these structures should help unlock the enigma of the emergence and evolution of dsDNA viruses and inform bioengineering efforts based on these viruses. PMID:29177192

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders.

PubMed

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Okun, Ilya

2016-05-25

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2-2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41-3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer's disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis.

AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders

PubMed Central

Ivachtchenko, Alexandre V.; Lavrovsky, Yan; Okun, Ilya

2016-01-01

Lack of efficacy of many new highly selective and specific drug candidates in treating diseases with poorly understood or complex etiology, as are many of central nervous system (CNS) diseases, encouraged an idea of developing multi-modal (multi-targeted) drugs. In this manuscript, we describe molecular pharmacology, in vitro ADME, pharmacokinetics in animals and humans (part of the Phase I clinical studies), bio-distribution, bioavailability, in vivo efficacy, and safety profile of the multimodal drug candidate, AVN-101. We have carried out development of a next generation drug candidate with a multi-targeted mechanism of action, to treat CNS disorders. AVN-101 is a very potent 5-HT7 receptor antagonist (Ki = 153 pM), with slightly lesser potency toward 5-HT6, 5-HT2A, and 5HT-2C receptors (Ki = 1.2–2.0 nM). AVN-101 also exhibits a rather high affinity toward histamine H1 (Ki = 0.58 nM) and adrenergic α2A, α2B, and α2C (Ki = 0.41–3.6 nM) receptors. AVN-101 shows a good oral bioavailability and facilitated brain-blood barrier permeability, low toxicity, and reasonable efficacy in animal models of CNS diseases. The Phase I clinical study indicates the AVN-101 to be well tolerated when taken orally at doses of up to 20 mg daily. It does not dramatically influence plasma and urine biochemistry, nor does it prolong QT ECG interval, thus indicating low safety concerns. The primary therapeutic area for AVN-101 to be tested in clinical trials would be Alzheimer’s disease. However, due to its anxiolytic and anti-depressive activities, there is a strong rational for it to also be studied in such diseases as general anxiety disorders, depression, schizophrenia, and multiple sclerosis. PMID:27232215

Revolution rather than rotation of AAA+ hexameric phi29 nanomotor for viral dsDNA packaging without coiling☆

PubMed Central

Schwartz, Chad; De Donatis, Gian Marco; Zhang, Hui; Fang, Huaming; Guo, Peixuan

2013-01-01

It has long been believed that the DNA-packaging motor of dsDNA viruses utilizes a rotation mechanism. Here we report a revolution rather than rotation mechanism for the bacteriophage phi29 DNA packaging motor. The phi29 motor contains six copies of the ATPase (Schwartz et al., this issue); ATP binding to one ATPase subunit stimulates the ATPase to adopt a conformation with a high affinity for dsDNA. ATP hydrolysis induces a new conformation with a lower affinity, thus transferring the dsDNA to an adjacent subunit by a power stroke. DNA revolves unidirectionally along the hexameric channel wall of the ATPase, but neither the dsDNA nor the ATPase itself rotates along its own axis. One ATP is hydrolyzed in each transitional step, and six ATPs are consumed for one helical turn of 360°. Transition of the same dsDNA chain along the channel wall, but at a location 60° different from the last contact, urges dsDNA to move forward 1.75 base pairs each step (10.5 bp per turn/6ATP=1.75 bp per ATP). Each connector subunit tilts with a left-handed orientation at a 30° angle in relation to its vertical axis that runs anti-parallel to the right-handed dsDNA helix, facilitating the one-way traffic of dsDNA. The connector channel has been shown to cause four steps of transition due to four positively charged lysine rings that make direct contact with the negatively charged DNA phosphate backbone. Translocation of dsDNA into the procapsid by revolution avoids the difficulties during rotation that are associated with DNA supercoiling. Since the revolution mechanism can apply to any stoichiometry, this motor mechanism might reconcile the stoichiometry discrepancy in many phage systems where the ATPase has been found as a tetramer, hexamer, or nonamer. PMID:23763768

The Folding of de Novo Designed Protein DS119 via Molecular Dynamics Simulations

PubMed Central

Wang, Moye; Hu, Jie; Zhang, Zhuqing

2016-01-01

As they are not subjected to natural selection process, de novo designed proteins usually fold in a manner different from natural proteins. Recently, a de novo designed mini-protein DS119, with a βαβ motif and 36 amino acids, has folded unusually slowly in experiments, and transient dimers have been detected in the folding process. Here, by means of all-atom replica exchange molecular dynamics (REMD) simulations, several comparably stable intermediate states were observed on the folding free-energy landscape of DS119. Conventional molecular dynamics (CMD) simulations showed that when two unfolded DS119 proteins bound together, most binding sites of dimeric aggregates were located at the N-terminal segment, especially residues 5–10, which were supposed to form β-sheet with its own C-terminal segment. Furthermore, a large percentage of individual proteins in the dimeric aggregates adopted conformations similar to those in the intermediate states observed in REMD simulations. These results indicate that, during the folding process, DS119 can easily become trapped in intermediate states. Then, with diffusion, a transient dimer would be formed and stabilized with the binding interface located at N-terminals. This means that it could not quickly fold to the native structure. The complicated folding manner of DS119 implies the important influence of natural selection on protein-folding kinetics, and more improvement should be achieved in rational protein design. PMID:27128902

Commentary: PhDs in Biochemistry Education--5 Years Later

ERIC Educational Resources Information Center

Offerdahl, Erika G.; Momsen, Jennifer L.; Osgood, Marcy

2014-01-01

In this commentary, the discussion of PhDs in biochemistry education research is expanded to explore a number of diverse pathways leading to a competitive research program in biochemistry education research.

[Targeted public funding for health research in the Netherlands].

PubMed

Viergever, Roderik F; Hendriks, Thom C C

2014-01-01

The Dutch government funds health research in several ways. One component of public funding consists of funding programmes issued by the Netherlands Organisation for Health Research and Development (ZonMw). The majority of ZonMw's programmes provide funding for research in specific health research areas. Such targeted funding plays an important role in addressing knowledge gaps and in generating products for which there is a need. Good governance of the allocation of targeted funding for health research requires three elements: a research agenda, an overview of the health research currently being conducted, and a transparent decision-making process regarding the distribution of funds. In this article, we describe how public funding for health research is organized in the Netherlands and how the allocation of targeted funds is governed. By describing the questions that the current model of governance raises, we take a first step towards a debate about the governance of targeted public funding for health research in the Netherlands.

Suppressed decays of D(s)(+) mesons to two pseudoscalar mesons.

PubMed

Adams, G S; Anderson, M; Cummings, J P; Danko, I; Hu, D; Moziak, B; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H; Yang, F; Artuso, M; Blusk, S; Khalil, S; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Naik, P; Briere, R A; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Cassel, D G; Duboscq, J E; Ehrlich, R; Fields, L; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Mohapatra, D; Onyisi, P U E; Patterson, J R; Peterson, D; Riley, D; Ryd, A; Sadoff, A J; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Athar, S B; Patel, R; Yelton, J; Rubin, P; Eisenstein, B I; Karliner, I; Lowrey, N; Selen, M; White, E J; Wiss, J; Mitchell, R E; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Zweber, P; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Ernst, J; Ecklund, K M; Severini, H; Love, W; Savinov, V; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Ge, J Y; Miller, D H; Sanghi, B; Shipsey, I P J; Xin, B

2007-11-09

Using data collected near the D{s}{*+}D{s}{-} peak production energy E_{cm}=4170 MeV by the CLEO-c detector, we study the decays of D{s}{+} mesons to two pseudoscalar mesons. We report on searches for the singly Cabibbo-suppressed D{s}{+} decay modes K{+}eta, K{+}eta', pi{+}K{S}{0}, K{+}pi{0}, and the isospin-forbidden decay mode D{s}{+}-->pi{+}pi{0}. We normalize with respect to the Cabibbo-favored D{s}{+} modes pi{+}eta, pi{+}eta', and K{+}K{S}{0}, and obtain ratios of branching fractions: B(D{s}{+}-->K{+}eta)/B(D{s}{+}-->pi{+}eta)=(8.9+/-1.5+/-0.4)%, B(D{s}{+}-->K{+}eta')/B(D{s}{+}-->pi{+}eta')=(4.2+/-1.3+/-0.3)%, B(D{s}{+}-->pi{+}K{S}{0})/B(D{s}{+}-->K{+}K{S}{0})=(8.2+/-0.9+/-0.2)%, B(D{s}{+}-->K{+}pi{0})/B(D{s}{+}-->K{+}K{S}{0})=(5.5+/-1.3+/-0.7)%, and B(D{s}{+}-->pi{+}pi{0})/B(D{s}{+}-->K{+}K{S}{0})<4.1% at 90% C.L., where the uncertainties are statistical and systematic, respectively.

Development of a new real-time GNSS data analysis system in GEONET for rapid Mw estimates in Japan

NASA Astrophysics Data System (ADS)

Kawamoto, S.; Miyagawa, K.; Yahagi, T.; Yamaguchi, K.; Tsuji, H.; Nishimura, T.; Ohta, Y.; Hino, R.; Miura, S.

2013-12-01

The 2011 off the Pacific Coast of Tohoku Earthquake (Mw 9.0) occurred on March 11, 2011. The earthquake and following tsunami caused serious damages to the broad coastal area of east Japan. Japan Meteorological Agency (JMA) operates the Tsunami Warning system, which is designed to forecast the tsunami height and its arrival time around 3 minutes after a large event. However, the first estimated magnitude of Mj, which was used for Tsunami Warning issuance, was far below the real one at the Tohoku event because of a saturation problem. In principle, as well as most other magnitude scales, Mj is saturated at certain values around 8.0. On the other hand, Mw represents the earthquake energy itself and it can be directly calculated by permanent displacements derived from geodetic measurements without the saturation problem. GNSS Earth Observation Network System (GEONET) is one of the densest real-time GNSS networks in the world operated by Geospatial Information Authority of Japan (GSI). The GEONET data and recent rapid advancement of GNSS analysis techniques motivate us to develop a new system for tackling the tsunami disasters. In order to provide the more reliable magnitude for Tsunami Warning, GSI and Tohoku University have jointly developed a new real-time analysis system in GEONET for quasi real-time Mw estimation. Its targets are large earthquakes, especially ones of Mw > 8.0, which would be saturated by the Tsunami Warning system. The real-time analysis system in GEONET mainly consists of three parts: (1) real-time GNSS positioning, (2) automated extraction of displacement fields due to the large earthquake, and (3) automated estimation of Mw by an approximated single rectangular fault. The positions of each station are calculated by using RTKLIB 2.4.1 (Takasu, 2011) with the baseline mode and the predicted part of the IGS Ultra Rapid precise orbit. For the event detection, we adopt the 'RAPiD' algorithm (Ohta et al., 2012) or Earthquake Early Warning issued by

High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

PubMed Central

Oliveira, Rodrigo C.; Oliveira, Isabela S.; Santiago, Mittermayer B.; Sousa Atta, Maria L. B.; Atta, Ajax M.

2015-01-01

We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA) dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA). Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction. PMID:26583157

Evaluation of glycodendron and synthetically-modified dextran clearing agents for multi-step targeting of radioisotopes for molecular imaging and radioimmunotherapy

PubMed Central

Cheal, Sarah M.; Yoo, Barney; Boughdad, Sarah; Punzalan, Blesida; Yang, Guangbin; Dilhas, Anna; Torchon, Geralda; Pu, Jun; Axworthy, Don B.; Zanzonico, Pat; Ouerfelli, Ouathek; Larson, Steven M.

2014-01-01

A series of N-acetylgalactosamine-dendrons (NAG-dendrons) and dextrans bearing biotin moieties were compared for their ability to complex with and sequester circulating bispecific anti-tumor antibody (scFv4) streptavidin (SA) fusion protein (scFv4-SA) in vivo, to improve tumor to normal tissue concentration ratios for targeted radioimmunotherapy and diagnosis. Specifically, a total of five NAG-dendrons employing a common synthetic scaffold structure containing 4, 8, 16, or 32 carbohydrate residues and a single biotin moiety were prepared (NAGB), and for comparative purposes, a biotinylated-dextran with average molecular weight (MW) of 500 kD was synthesized from amino-dextran (DEXB). One of the NAGB compounds, CA16, has been investigated in humans; our aim was to determine if other NAGB analogs (e.g. CA8 or CA4) were bioequivalent to CA16 and/or better suited as MST reagents. In vivo studies included dynamic positron-emission tomography (PET) imaging of 124I-labelled-scFv4-SA clearance and dual-label biodistribution studies following multi-step targeting (MST) directed at subcutaneous (s.c.) human colon adenocarcinoma xenografts in mice. The MST protocol consists of three injections: first, a bispecific antibody specific for an anti-tumor associated glycoprotein (TAG-72) single chain genetically-fused with SA (scFv4-SA); second, CA16 or other clearing agent; and third, radiolabeled biotin. We observed using PET imaging of 124I-labelled-scFv4-SA clearance that the spatial arrangement of ligands conjugated to NAG (i.e. biotin) can impact the binding to antibody in circulation and subsequent liver uptake of the NAG-antibody complex. Also, NAGB CA32-LC or CA16-LC can be utilized during MST to achieve comparable tumor- to-blood ratios and absolute tumor uptake seen previously with CA16. Finally, DEXB was equally effective as NAGB CA32-LC at lowering scFv4-SA in circulation, but at the expense of reducing absolute tumor uptake of radiolabeled biotin. PMID:24219178

Reaction of the immune system to low-level RF/MW exposures.

PubMed

Szmigielski, Stanislaw

2013-06-01

Radiofrequency (RF) and microwave (MW) radiation have been used in the modern world for many years. The rapidly increasing use of cellular phones in recent years has seen increased interest in relation to the possible health effects of exposure to RF/MW radiation. In 2011 a group of international experts organized by the IARC (International Agency for Research on Cancer in Lyon) concluded that RF/MW radiations should be listed as a possible carcinogen (group 2B) for humans. The incomplete knowledge of RF/MW-related cancer risks has initiated searches for biological indicators sensitive enough to measure the "weak biological influence" of RF/MWs. One of the main candidates is the immune system, which is able to react in a measurable way to discrete environmental stimuli. In this review, the impacts of weak RF/MW fields, including cell phone radiation, on various immune functions, both in vitro and in vivo, are discussed. The bulk of available evidence clearly indicates that various shifts in the number and/or activity of immunocompetent cells are possible, however the results are inconsistent. For example, a number of lymphocyte functions have been found to be enhanced and weakened within single experiments based on exposure to similar intensities of MW radiation. Certain premises exist which indicate that, in general, short-term exposure to weak MW radiation may temporarily stimulate certain humoral or cellular immune functions, while prolonged irradiation inhibits the same functions. Copyright © 2013. Published by Elsevier B.V.

Characterization of wash-off from urban impervious surfaces and SuDS design criteria for source control under semi-arid conditions.

PubMed

Andrés-Doménech, Ignacio; Hernández-Crespo, Carmen; Martín, Miguel; Andrés-Valeri, Valerio C

2018-01-15

Knowledge about pollutant wash-off from urban impervious surfaces is a key feature for developing effective management strategies. Accordingly, further information is required about urban areas under semi-arid climate conditions at the sub-catchment scale. This is important for designing source control systems for pollution. In this study, a characterization of pollutant wash-off has been performed over sixteen months, at the sub-catchment scale for urban roads as impervious surfaces. The study was conducted in Valencia, Spain, a city with a Mediterranean climate. The results show high event mean concentrations for suspended solids (98mg/l), organic matter (142mgCOD/l, 25mgBOD 5 /l), nutrients (3.7mgTN/l, 0.4mgTP/l), and metals (0.23, 0.32, 0.62 and 0.17mg/l for Cu, Ni, Pb, and Zn, respectively). The results of the runoff characterization highlight the need to control this pollution at its source, separately from wastewater because of their different characteristics. The wash-off, defined in terms of mobilized mass (g/m 2 ) fits well with both process-based and statistical models, with the runoff volume and rainfall depth being the main explanatory variables. Based on these results and using information collected from hydrographs and pollutographs, an approach for sizing sustainable urban drainage systems (SuDS), focusing on water quality and quantity variables, has been proposed. By setting a concentration-based target (TSS discharged to receiving waters <35mg/l), the results indicate that for a SuDS type detention basin (DB), an off-line configuration performs better than an on-line configuration. The resulting design criterion, expressed as SuDS volume per unit catchment area, assuming a DB type SuDS, varies between 7 and 10l/m 2 . Copyright © 2017 Elsevier B.V. All rights reserved.

Nanogenerators consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes using flexoelectric effects

PubMed Central

Han, Jin Kyu; Jeon, Do Hyun; Cho, Sam Yeon; Kang, Sin Wook; Yang, Sun A.; Bu, Sang Don; Myung, Sung; Lim, Jongsun; Choi, Moonkang; Lee, Minbaek; Lee, Min Ku

2016-01-01

We report the first attempt to prepare a flexoelectric nanogenerator consisting of direct-grown piezoelectrics on multi-walled carbon nanotubes (mwCNT). Direct-grown piezoelectrics on mwCNTs are formed by a stirring and heating method using a Pb(Zr0.52Ti0.48)O3 (PZT)-mwCNT precursor solution. We studied the unit cell mismatch and strain distribution of epitaxial PZT nanoparticles, and found that lattice strain is relaxed along the growth direction. A PZT-mwCNT nanogenerator was found to produce a peak output voltage of 8.6 V and an output current of 47 nA when a force of 20 N is applied. Direct-grown piezoelectric nanogenerators generate a higher voltage and current than simple mixtures of PZT and CNTs resulting from the stronger connection between PZT crystals and mwCNTs and an enhanced flexoelectric effect caused by the strain gradient. These experiments represent a significant step toward the application of nanogenerators using piezoelectric nanocomposite materials. PMID:27406631

Prediction of effective RNA interference targets and pathway-related genes in lepidopteran insects by RNA sequencing analysis.

PubMed

Guan, Ruo-Bing; Li, Hai-Chao; Miao, Xue-Xia

2018-06-01

When using RNA interference (RNAi) to study gene functions in Lepidoptera insects, we discovered that some genes could not be suppressed; instead, their expression levels could be up-regulated by double-stranded RNA (dsRNA). To predict which genes could be easily silenced, we treated the Asian corn borer (Ostrinia furnacalis) with dsGFP (green fluorescent protein) and dsMLP (muscle lim protein). A transcriptome sequence analysis was conducted using the cDNAs 6 h after treatment with dsRNA. The results indicated that 160 genes were up-regulated and 44 genes were down-regulated by the two dsRNAs. Then, 50 co-up-regulated, 25 co-down-regulated and 43 unaffected genes were selected to determine their RNAi responses. All the 25 down-regulated genes were knocked down by their corresponding dsRNA. However, several of the up-regulated and unaffected genes were up-regulated when treated with their corresponding dsRNAs instead of being knocked down. The genes up-regulated by the dsGFP treatment may be involved in insect immune responses or the RNAi pathway. When the immune-related genes were excluded, only seven genes were induced by dsGFP, including ago-2 and dicer-2. These results not only provide a reference for efficient RNAi target predications, but also provide some potential RNAi pathway-related genes for further study. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Network anomaly detection system with optimized DS evidence theory.

PubMed

Liu, Yuan; Wang, Xiaofeng; Liu, Kaiyu

2014-01-01

Network anomaly detection has been focused on by more people with the fast development of computer network. Some researchers utilized fusion method and DS evidence theory to do network anomaly detection but with low performance, and they did not consider features of network-complicated and varied. To achieve high detection rate, we present a novel network anomaly detection system with optimized Dempster-Shafer evidence theory (ODS) and regression basic probability assignment (RBPA) function. In this model, we add weights for each sensor to optimize DS evidence theory according to its previous predict accuracy. And RBPA employs sensor's regression ability to address complex network. By four kinds of experiments, we find that our novel network anomaly detection model has a better detection rate, and RBPA as well as ODS optimization methods can improve system performance significantly.

Local gene silencing in plants via synthetic dsRNA and carrier peptide.

PubMed

Numata, Keiji; Ohtani, Misato; Yoshizumi, Takeshi; Demura, Taku; Kodama, Yutaka

2014-10-01

Quick and facile transient RNA interference (RNAi) is one of the most valuable plant biotechnologies for analysing plant gene functions. To establish a novel double-strand RNA (dsRNA) delivery system for plants, we developed an ionic complex of synthetic dsRNA with a carrier peptide in which a cell-penetrating peptide is fused with a polycation sequence as a gene carrier. The dsRNA-peptide complex is 100-300 nm in diameter and positively charged. Infiltration of the complex into intact leaf cells of Arabidopsis thaliana successfully induced rapid and efficient down-regulation of exogenous and endogenous genes such as yellow fluorescent protein and chalcone synthase. The present method realizes quick and local gene silencing in specific tissues and/or organs in plants. © 2014 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Biotechnological engineering of heparin/heparan sulphate: a novel area of multi-target drug discovery.

PubMed

Rusnati, Marco; Oreste, Pasqua; Zoppetti, Giorgio; Presta, Marco

2005-01-01

Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA not l&r arrow N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target "biotechnological heparin/HS" molecules are outlined.

A multi-layered active target for the study of neutron-unbound nuclides at NSCL

NASA Astrophysics Data System (ADS)

Freeman, Jessica; Gueye, Paul; Redpath, Thomas; MoNA Collaboration

2017-01-01

The characteristics of neutron-unbound nuclides were investigated using a multi-layered Si/Be active target designed for use with the MoNA/LISA setup at the National Superconducting Cyclotron (NSCL). The setup consists of the MoNA/LISA arrays (for neutron detection) and a superconducting sweeper magnet (for charged separation) to identify products following the decay of neutron unbound states. The segmented target consisted of three 700 mg/cm2 beryllium targets and four 0.14 mm thick 62x62 mm2 silicon detectors. As a commissioning experiment for the target the decay of two-neutron unbound 26O populated in a one-proton removal reaction from a radioactive 27F beam was performed. The 27F secondary radioactive beam from the NSCL's Coupled Cyclotron Facility was produced from the fragmentation of a 140 MeV/u 48Ca beam incident on a thick beryllium target and then cleanly selected by the A1900 fragment separator. The energy loss and position spectra of the incoming beam and reaction products were used to calibrate the Silicon detectors to within 1.5% in both energy and position. A dedicated Geant4 model of the target was developed to simulate the energy loss within the target. A description of the experimental setup, simulation work, and energy and position calibration will be presented. DoE/NNSA - DE-NA0000979.

78 FR 50437 - U.S. Extractive Industries Transparency Initiative Multi-Stakeholder Group (USEITI MSG) Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-19

... DEPARTMENT OF THE INTERIOR Office of the Secretary [Docket No. ONRR-2012-0003; DS63600000 DR2PS0000.PX8000 134D0102R2] U.S. Extractive Industries Transparency Initiative Multi- Stakeholder Group...: This notice announces the next three meetings of the United States Extractive Industries Transparency...

78 FR 64525 - U.S. Extractive Industries Transparency Initiative Multi-Stakeholder Group (USEITI MSG) Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... DEPARTMENT OF THE INTERIOR Office of the Secretary [Docket No. ONRR-2012-0003; DS63600000 DR2PS0000.PX8000 134D0102R2] U.S. Extractive Industries Transparency Initiative Multi- Stakeholder Group...: This notice announces the rescheduling of the U.S. Extractive Industries Transparency Initiative...

78 FR 60304 - U.S. Extractive Industries Transparency Initiative Multi-Stakeholder Group (USEITI MSG) Advisory...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-01

... DEPARTMENT OF THE INTERIOR Office of the Secretary [Docket No. ONRR-2012-0003; DS63600000 DR2PS0000.PX8000 134D0102R2] U.S. Extractive Industries Transparency Initiative Multi- Stakeholder Group...: This notice announces the meeting date change of the United States Extractive Industries Transparency...

Multi-laboratory evaluations of the performance of Catellicoccus marimammalium PCR assays developed to target gull fecal sources

EPA Science Inventory

Here we report results from a multi-laboratory (n=11) evaluation of four different PCR methods targeting the 16S rRNA gene of Catellicoccus marimammalium used to detect fecal contamination from birds in coastal environments. The methods included conventional end-point PCR, a SYBR...

Design and test of a 2.25-MW transformer rectifier assembly

NASA Technical Reports Server (NTRS)

Cormier, R.; Daeges, J.

1989-01-01

A new 2.25-MW transformer rectifier assembly was fabricated for DSS-13 at Goldstone, California. The transformer rectifier will provide constant output power of 2.25 MW at any voltage from 31 kV to 125 kV. This will give a new capability of 1 MW of RF power at X-band, provided appropriate microwave tubes are in the power amplifier. A description of the design and test results is presented.

Integration of multi-source and multi-scale datasets for 3D structural modeling for subsurface exploration targeting, Luanchuan Mo-polymetallic district, China

NASA Astrophysics Data System (ADS)

Wang, Gongwen; Ma, Zhenbo; Li, Ruixi; Song, Yaowu; Qu, Jianan; Zhang, Shouting; Yan, Changhai; Han, Jiangwei

2017-04-01

In this paper, multi-source (geophysical, geochemical, geological and remote sensing) datasets were used to construct multi-scale (district-, deposit-, and orebody-scale) 3D geological models and extract 3D exploration criteria for subsurface Mo-polymetallic exploration targeting in the Luanchuan district in China. The results indicate that (i) a series of region-/district-scale NW-trending thrusts controlled main Mo-polymetallic forming, and they were formed by regional Indosinian Qinling orogenic events, the secondary NW-trending district-scale folds and NE-trending faults and the intrusive stock structure are produced based on thrust structure in Caledonian-Indosinian orogenic events; they are ore-bearing zones and ore-forming structures; (ii) the NW-trending district-scale and NE-trending deposit-scale normal faults were crossed and controlled by the Jurassic granite stocks in 3D space, they are associated with the magma-skarn Mo polymetallic mineralization (the 3D buffer distance of ore-forming granite stocks is 600 m) and the NW-trending hydrothermal Pb-Zn deposits which are surrounded by the Jurassic granite stocks and constrained by NW-trending or NE-trending faults (the 3D buffer distance of ore-forming fault is 700 m); and (iii) nine Mo polymetallic and four Pb-Zn targets were identified in the subsurface of the Luanchuan district.

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) Scale: Comprehensive Assessment of Psychopathology in Down Syndrome.

PubMed

Dekker, Alain D; Sacco, Silvia; Carfi, Angelo; Benejam, Bessy; Vermeiren, Yannick; Beugelsdijk, Gonny; Schippers, Mieke; Hassefras, Lyanne; Eleveld, José; Grefelman, Sharina; Fopma, Roelie; Bomer-Veenboer, Monique; Boti, Mariángeles; Oosterling, G Danielle E; Scholten, Esther; Tollenaere, Marleen; Checkley, Laura; Strydom, André; Van Goethem, Gert; Onder, Graziano; Blesa, Rafael; Zu Eulenburg, Christine; Coppus, Antonia M W; Rebillat, Anne-Sophie; Fortea, Juan; De Deyn, Peter P

2018-01-01

People with Down syndrome (DS) are prone to develop Alzheimer's disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. 83 behavioral items in 12 clinically defined sections were evaluated. The central aim was to identify items that change in relation to the dementia status, and thus may differentiate between diagnostic groups. Structured interviews were conducted with informants of persons with DS without dementia (DS, n = 149), with questionable dementia (DS+Q, n = 65), and with diagnosed dementia (DS+AD, n = 67). First exploratory data suggest promising interrater, test-retest, and internal consistency reliability measures. Concerning item relevance, group comparisons revealed pronounced increases in frequency and severity in items of anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and eating/drinking behavior. The proportion of individuals presenting an increase was highest in DS+AD, intermediate in DS+Q, and lowest in DS. Interestingly, among DS+Q individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy, and depressive symptoms, suggesting that these changes occur early in the course of AD. Future efforts should optimize the scale based on current results and clinical experiences, and further study applicability, reliability, and validity. Future application of the scale in daily care may aid caregivers to understand changes, and contribute to timely interventions and adaptation of caregiving.

The Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) Scale: Comprehensive Assessment of Psychopathology in Down Syndrome

PubMed Central

Dekker, Alain D.; Sacco, Silvia; Carfi, Angelo; Benejam, Bessy; Vermeiren, Yannick; Beugelsdijk, Gonny; Schippers, Mieke; Hassefras, Lyanne; Eleveld, José; Grefelman, Sharina; Fopma, Roelie; Bomer-Veenboer, Monique; Boti, Mariángeles; Oosterling, G. Danielle E.; Scholten, Esther; Tollenaere, Marleen; Checkley, Laura; Strydom, André; Van Goethem, Gert; Onder, Graziano; Blesa, Rafael; zu Eulenburg, Christine; Coppus, Antonia M.W.; Rebillat, Anne-Sophie; Fortea, Juan; De Deyn, Peter P.

2018-01-01

People with Down syndrome (DS) are prone to develop Alzheimer’s disease (AD). Behavioral and psychological symptoms of dementia (BPSD) are core features, but have not been comprehensively evaluated in DS. In a European multidisciplinary study, the novel Behavioral and Psychological Symptoms of Dementia in Down Syndrome (BPSD-DS) scale was developed to identify frequency and severity of behavioral changes taking account of life-long characteristic behavior. 83 behavioral items in 12 clinically defined sections were evaluated. The central aim was to identify items that change in relation to the dementia status, and thus may differentiate between diagnostic groups. Structured interviews were conducted with informants of persons with DS without dementia (DS, n = 149), with questionable dementia (DS+Q, n = 65), and with diagnosed dementia (DS+AD, n = 67). First exploratory data suggest promising interrater, test-retest, and internal consistency reliability measures. Concerning item relevance, group comparisons revealed pronounced increases in frequency and severity in items of anxiety, sleep disturbances, agitation & stereotypical behavior, aggression, apathy, depressive symptoms, and eating/drinking behavior. The proportion of individuals presenting an increase was highest in DS+AD, intermediate in DS+Q, and lowest in DS. Interestingly, among DS+Q individuals, a substantial proportion already presented increased anxiety, sleep disturbances, apathy, and depressive symptoms, suggesting that these changes occur early in the course of AD. Future efforts should optimize the scale based on current results and clinical experiences, and further study applicability, reliability, and validity. Future application of the scale in daily care may aid caregivers to understand changes, and contribute to timely interventions and adaptation of caregiving. PMID:29689719

A low-loss, single-pole, four-throw RF MEMS switch driven by a double stop comb drive

NASA Astrophysics Data System (ADS)

Kang, S.; Kim, H. C.; Chun, K.

2009-03-01

Our goal was to develop a single-pole four-throw (SP4T) radio frequency microelectromechanical system (RF MEMS) switch for band selection in a multi-band, multi-mode, front-end module of a wireless transceiver system. The SP4T RF MEMS switch was based on an arrangement of four single-pole single-throw (SPST) RF MEMS switches. The SP4T RF MEMS switch was driven by a double stop (DS) comb drive, with a lateral resistive contact, and composed of single crystalline silicon (SCS) on glass. A large contact force at a low-drive voltage was achieved by electrostatic actuation of the DS comb drive. Good RF characteristics were achieved by the large contact force and the lateral resistive Au-to-Au contact. Mechanical reliability was achieved by using SCS which has no residual stress as a structure material. The developed SP4T RF MEMS switch has a drive voltage of 15 V, an insertion loss below 0.31 dB at 6 GHz after more than one million cycles under a 10 mW signal, a return loss above 20 dB and an isolation value above 36 dB.

KiDS-450: tomographic cross-correlation of galaxy shear with Planck lensing

NASA Astrophysics Data System (ADS)

Harnois-Déraps, Joachim; Tröster, Tilman; Chisari, Nora Elisa; Heymans, Catherine; van Waerbeke, Ludovic; Asgari, Marika; Bilicki, Maciej; Choi, Ami; Erben, Thomas; Hildebrandt, Hendrik; Hoekstra, Henk; Joudaki, Shahab; Kuijken, Konrad; Merten, Julian; Miller, Lance; Robertson, Naomi; Schneider, Peter; Viola, Massimo

2017-10-01

We present the tomographic cross-correlation between galaxy lensing measured in the Kilo Degree Survey (KiDS-450) with overlapping lensing measurements of the cosmic microwave background (CMB), as detected by Planck 2015. We compare our joint probe measurement to the theoretical expectation for a flat Λ cold dark matter cosmology, assuming the best-fitting cosmological parameters from the KiDS-450 cosmic shear and Planck CMB analyses. We find that our results are consistent within 1σ with the KiDS-450 cosmology, with an amplitude re-scaling parameter AKiDS = 0.86 ± 0.19. Adopting a Planck cosmology, we find our results are consistent within 2σ, with APlanck = 0.68 ± 0.15. We show that the agreement is improved in both cases when the contamination to the signal by intrinsic galaxy alignments is accounted for, increasing A by ∼0.1. This is the first tomographic analysis of the galaxy lensing - CMB lensing cross-correlation signal, and is based on five photometric redshift bins. We use this measurement as an independent validation of the multiplicative shear calibration and of the calibrated source redshift distribution at high redshifts. We find that constraints on these two quantities are strongly correlated when obtained from this technique, which should therefore not be considered as a stand-alone competitive calibration tool.

MW-Class Electric Propulsion System Designs

NASA Technical Reports Server (NTRS)

LaPointe, Michael R.; Oleson, Steven; Pencil, Eric; Mercer, Carolyn; Distefano, Salvador

2011-01-01

Electric propulsion systems are well developed and have been in commercial use for several years. Ion and Hall thrusters have propelled robotic spacecraft to encounters with asteroids, the Moon, and minor planetary bodies within the solar system, while higher power systems are being considered to support even more demanding future space science and exploration missions. Such missions may include orbit raising and station-keeping for large platforms, robotic and human missions to near earth asteroids, cargo transport for sustained lunar or Mars exploration, and at very high-power, fast piloted missions to Mars and the outer planets. The Advanced In-Space Propulsion Project, High Efficiency Space Power Systems Project, and High Power Electric Propulsion Demonstration Project were established within the NASA Exploration Technology Development and Demonstration Program to develop and advance the fundamental technologies required for these long-range, future exploration missions. Under the auspices of the High Efficiency Space Power Systems Project, and supported by the Advanced In-Space Propulsion and High Power Electric Propulsion Projects, the COMPASS design team at the NASA Glenn Research Center performed multiple parametric design analyses to determine solar and nuclear electric power technology requirements for representative 300-kW class and pulsed and steady-state MW-class electric propulsion systems. This paper describes the results of the MW-class electric power and propulsion design analysis. Starting with the representative MW-class vehicle configurations, and using design reference missions bounded by launch dates, several power system technology improvements were introduced into the parametric COMPASS simulations to determine the potential system level benefits such technologies might provide. Those technologies providing quantitative system level benefits were then assessed for technical feasibility, cost, and time to develop. Key assumptions and primary

DS2 Container and Weatherproofing Study

DTIC Science & Technology

1990-12-01

compatible with polyurethane based coating systems in general? Is it compatible with alkyd -based coatings? 10. How well do the labels placed on the...of the (older) alkyd enamel and (more recently) polyurethane camouflage coatings, leading eventually to seepage of the DS2. A shrink-wrap overpack...by John Wiley and Sons, Inc., Vol. 2, pp. 118- 119; Vol. 4, p. 3 and pp. 284-295; Vol. I, p. 133. 8. Fiber Composite Hybrid Materials, N.L. Hancox

Startup, Commissioning and Operation of Fenyi 100MW CFB Boiler

NASA Astrophysics Data System (ADS)

Wang, Zhiwei; Yu, Wugao; Bo, Shi

The first 100MW CFB boiler, designed by the Thermal Power Research Institute and manufactured by Harbin Boiler Company Limited, has been successfully running in Jiangxi Fenyi Power Plant since 2003. Local high ash content anthracite and lean coal that are very difficult to burn out are used in the 100 MW CFB boiler. The results of the 100MW CFB boiler shows that the CFB boiler can run in 30% MCR and startup with two under bed burners, and the boiler efficiency higher than 88% can be got after the combustion modification test. The CFB boiler can be operated with full load and reaches design parameters. The emissions of NO, N2O and CO are less than 7Omg/m3, 30mg/m3, and 125mg/m3, respectively, and SO2 less than 400mg/m3 after limestone injection. The bottom ash temperature from bed ash coolers is less than 120°C after its modification. Coal blockage at the coal storage silo is the main problem influencing the CFB boiler continuous operation. The running experiences for 5 years proved that the CFB boiler performance is successful, and the results were applied in 210 MW and 330 MW CFB Boiler design of Fenyi Power Plant.

Invasive species compendium: Salvinia molesta D.S. Mitchell

USDA-ARS?s Scientific Manuscript database

Salvinia molesta D.S. Mitchell is an invasive aquatic fern native to a small area of south-eastern Brazil. It has spread throughout the world, forming thick mats of vegetation that decrease dissolved oxygen and pH while outcompeting native vegetation. It has been introduced and established into many...

Benzoate-mediated changes on expression profile of soluble proteins in Serratia sp. DS001.

PubMed

Pandeeti, E V P; Chinnaboina, M R; Siddavattam, D

2009-05-01

To assess differences in protein expression profile associated with shift in carbon source from succinate to benzoate in Serratia sp. DS001 using a proteomics approach. A basic proteome map was generated for the soluble proteins extracted from Serratia sp. DS001 grown in succinate and benzoate. The differently and differentially expressed proteins were identified using ImageMaster 2D Platinum software (GE Healthcare). The identity of the proteins was determined by employing MS or MS/MS. Important enzymes such as Catechol 1,2 dioxygenase and transcriptional regulators that belong to the LysR superfamily were identified. Nearly 70 proteins were found to be differentially expressed when benzoate was used as carbon source. Based on the protein identity and degradation products generated from benzoate it is found that ortho pathway is operational in Serratia sp. DS001. Expression profile of the soluble proteins associated with shift in carbon source was mapped. The study also elucidates degradation pathway of benzoate in Serratia sp. DS001 by correlating the proteomics data with the catabolites of benzoate.

Lightweight MgB2 superconducting 10 MW wind generator

NASA Astrophysics Data System (ADS)

Marino, I.; Pujana, A.; Sarmiento, G.; Sanz, S.; Merino, J. M.; Tropeano, M.; Sun, J.; Canosa, T.

2016-02-01

The offshore wind market demands a higher power rate and more reliable turbines in order to optimize capital and operational costs. The state-of-the-art shows that both geared and direct-drive conventional generators are difficult to scale up to 10 MW and beyond due to their huge size and weight. Superconducting direct-drive wind generators are considered a promising solution to achieve lighter weight machines. This work presents an innovative 10 MW 8.1 rpm direct-drive partial superconducting generator using MgB2 wire for the field coils. It has a warm iron rotor configuration with the superconducting coils working at 20 K while the rotor core and the armature are at ambient temperature. A cooling system based on cryocoolers installed in the rotor extracts the heat from the superconducting coils by conduction. The generator's main parameters are compared against a permanent magnet reference machine, showing a significant weight and size reduction. The 10 MW superconducting generator concept will be experimentally validated with a small-scale magnetic machine, which has innovative components such as superconducting coils, modular cryostats and cooling systems, and will have similar size and characteristics as the 10 MW generator.

The nature of the force-induced conformation transition of dsDNA studied by using single molecule force spectroscopy.

PubMed

Liu, Ningning; Bu, Tianjia; Song, Yu; Zhang, Wei; Li, Jinjing; Zhang, Wenke; Shen, Jiacong; Li, Hongbin

2010-06-15

Single-stranded DNA binding proteins (SSB) interact with single-stranded DNA (ssDNA) specifically. Taking advantage of this character, we have employed Bacillus subtilis SSB protein to investigate the nature of force-induced conformation transition of double-stranded DNA (dsDNA) by using AFM-based single molecule force spectroscopy (SMFS) technique. Our results show that, when a dsDNA is stretched beyond its contour length, the dsDNA is partially melted, producing some ssDNA segments which can be captured by SSB proteins. We have also systematically investigated the effects of stretching length, waiting time, and salt concentration on the conformation transition of dsDNA and SSB-ssDNA interactions, respectively. Furthermore, the effect of proflavine, a DNA intercalator, on the SSB-DNA interactions has been investigated, and the results indicate that the proflavine-saturated dsDNA can be stabilized to the extent that the dsDNA will no longer melt into ssDNA under the mechanical force even up to 150 pN, and no SSB-DNA interactions are detectable.

The Effects of Green Cards on the Wages and Innovations of New PhDs

ERIC Educational Resources Information Center

Lan, Xiaohuan

2013-01-01

Visa policies in the United States restrict job opportunities and job mobility for U.S.-trained PhDs who hold a temporary visa, a group that accounts for 40 percent of newly graduated PhDs in science and engineering. The Chinese Student Protection Act of 1992 (CSPA) allowed Chinese students to be eligible for permanent residence in the United…

Physical characteristics of GE Senographe Essential and DS digital mammography detectors.

PubMed

Ghetti, Caterina; Borrini, Adriano; Ortenzia, Ornella; Rossi, Raffaella; Ordóñez, Pedro L

2008-02-01

The purpose of this study was to investigate physical characteristics of two full field digital mammography (FFDM) systems (GE Senographe Essential and DS). Both are indirect conversion (x ray to light) alpha-Si flat panels coupled with a CsI(Tl) scintillator. The examined systems have the same pixel size (100 microm) but a different field of view: a conventional size 23 x 19.2 cm2 and a large field 24 X 30.7 cm2, specifically designed to image large breasts. In the GE Senographe Essential model relevant improvements in flat panel design were implemented and new deposition tools for metal, alpha-Si, and CsI(Tl) were introduced by GE. These changes in detector design are expected to be beneficial for advanced applications such as breast tomosynthesis. The presampling modulation transfer function (MTF), normalized noise power spectrum (NNPS), and detective quantum efficiency (DQE) were measured for a wide range of exposure (25-240 microGy) with a RQA-M2 technique (28 kVp with a Mo/Mo target/filter combination and 2 mm of additional aluminum filtration). At 1, 2, and at 4 lp/mm MTF is equal to 0.9, 0.76, and 0.46 for the conventional field detector and to 0.85, 0.59, and 0.24 for the large field detector. The latter detector exhibits an improved NNPS due to a lower electronic noise and a better DQE that reaches 60%. In addition a contrast-detail analysis was performed with CDMAM 3.4 phantom and CDCOM software: GE Senographe DS showed statistically significant poorer detection ability in comparison with the GE Senographe Essential. These results could have been expected, at least qualitatively, considering the relative DQE of the two systems.

Network Anomaly Detection System with Optimized DS Evidence Theory

PubMed Central

Liu, Yuan; Wang, Xiaofeng; Liu, Kaiyu

2014-01-01

Network anomaly detection has been focused on by more people with the fast development of computer network. Some researchers utilized fusion method and DS evidence theory to do network anomaly detection but with low performance, and they did not consider features of network—complicated and varied. To achieve high detection rate, we present a novel network anomaly detection system with optimized Dempster-Shafer evidence theory (ODS) and regression basic probability assignment (RBPA) function. In this model, we add weights for each senor to optimize DS evidence theory according to its previous predict accuracy. And RBPA employs sensor's regression ability to address complex network. By four kinds of experiments, we find that our novel network anomaly detection model has a better detection rate, and RBPA as well as ODS optimization methods can improve system performance significantly. PMID:25254258

The development and testing of the thermal break divertor monoblock target design delivering 20 MW m-2 heat load capability

NASA Astrophysics Data System (ADS)

Fursdon, M.; Barrett, T.; Domptail, F.; Evans, Ll M.; Luzginova, N.; Greuner, N. H.; You, J.-H.; Li, M.; Richou, M.; Gallay, F.; Visca, E.

2017-12-01

The design and development of a novel plasma facing component (for fusion power plants) is described. The component uses the existing ‘monoblock’ construction which consists of a tungsten ‘block’ joined via a copper interlayer to a through CuCrZr cooling pipe. In the new concept the interlayer stiffness and conductivity properties are tuned so that stress in the principal structural element of the component (the cooling pipe) is reduced. Following initial trials with off-the-shelf materials, the concept was realized by machined features in an otherwise solid copper interlayer. The shape and distribution of the features were tuned by finite element analyses subject to ITER structural design criterion in-vessel components (SDC-IC) design rules. Proof of concept mock-ups were manufactured using a two stage brazing process verified by tomography and micrographic inspection. Full assemblies were inspected using ultrasound and thermographic (SATIR) test methods at ENEA and CEA respectively. High heat flux tests using IPP’s GLADIS facility showed that 200 cycles at 20 MW m-2 and five cycles at 25 MW m-2 could be sustained without apparent component damage. Further testing and component development is planned.

Concentrating Solar Power Projects - Hami 50 MW CSP Project | Concentrating

Science.gov Websites

Solar Power | NREL Hami 50 MW CSP Project Status Date: April 6, 2018 Project Overview Project MW Status: Under construction Do you have more information, corrections, or comments? Background Technology: Power tower Status: Under construction Country: China City: Hami Region: Xinjiang Autonomous

Tumor targeting profiling of hyaluronan-coated lipid based-nanoparticles

NASA Astrophysics Data System (ADS)

Mizrahy, Shoshy; Goldsmith, Meir; Leviatan-Ben-Arye, Shani; Kisin-Finfer, Einat; Redy, Orit; Srinivasan, Srimeenakshi; Shabat, Doron; Godin, Biana; Peer, Dan

2014-03-01

Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression. Low Mw (LMw, <10 kDa) HA has been reported to provoke inflammatory responses, such as induction of cytokines, chemokines, reactive nitrogen species and growth factors. Herein, we prepared and characterized two types of HA coated (LMw and HMw) lipid-based targeted and stabilized nanoparticles (tsNPs) and tested their binding to tumor cells expressing the HA receptor (CD44), systemic immunotoxicity, and biodistribution in tumor bearing mice. In vitro, the Mw of the surface anchored HA had a significant influence on the affinity towards CD44 on B16F10 murine melanoma cells. LMw HA-tsNPs exhibited weak binding, while binding of tsNPs coated with HMw HA was characterized by high binding. Both types of tsNPs had no measured effect on cytokine induction in vivo following intravenous administration to healthy C57BL/6 mice suggesting no immune activation. HMw HA-tsNPs showed enhanced circulation time and tumor targeting specificity, mainly by accumulating in the tumor and its vicinity compared with LMw HA-tsNPs. Finally, we show that methotrexate (MTX), a drug commonly used in cancer chemotherapy, entrapped in HMw HA-tsNPs slowly diffused from the particles with a half-life of 13.75 days, and improved the therapeutic outcome in a murine B16F10 melanoma model compared with NPs suggesting an active cellular targeting beyond the Enhanced Permeability and Retention (EPR) effect. Taken together, these findings have major implications for the use of high molecular weight HA in nanomedicine as a selective and safe active cellular targeting moiety.Hyaluronan (HA), a naturally occurring high Mw (HMw) glycosaminoglycan, has been shown to play crucial roles in cell growth, embryonic development, healing processes, inflammation, and tumor development and progression

Concentrating Solar Power Projects - Delingha 50MW Thermal Oil Parabolic

Science.gov Websites

Trough project | Concentrating Solar Power | NREL Delingha 50MW Thermal Oil Parabolic Trough project Status Date: April 17, 2017 Project Overview Project Name: Delingha 50MW Thermal Oil Parabolic Contractor: IDOM : Thermal energy storage system engineering Plant Configuration Solar Field # of Loops: 190

Concentrating Solar Power Projects - Rayspower Yumen 50MW Thermal Oil

Science.gov Websites

Trough project | Concentrating Solar Power | NREL Rayspower Yumen 50MW Thermal Oil Trough project Status Date: January 31, 2017 Project Overview Project Name: Rayspower Yumen 50MW Thermal Oil . Plant Configuration Solar Field Heat-Transfer Fluid Type: Thermal oil Power Block Turbine Capacity

Concentrating Solar Power Projects - Gulang 100MW Thermal Oil Parabolic

Science.gov Websites

Trough project | Concentrating Solar Power | NREL Gulang 100MW Thermal Oil Parabolic Trough project Status Date: September 29, 2016 Project Overview Project Name: Gulang 100MW Thermal Oil Parabolic ): Webmaster Solar Participants Developer(s): Changzhou Royal Tech Solar Thermal Equipment Co., Ltd. Owner(s

Therapy reduction in patients with Down syndrome and myeloid leukemia: the international ML-DS 2006 trial.

PubMed

Uffmann, Madita; Rasche, Mareike; Zimmermann, Martin; von Neuhoff, Christine; Creutzig, Ursula; Dworzak, Michael; Scheffers, Lenie; Hasle, Henrik; Zwaan, C Michel; Reinhardt, Dirk; Klusmann, Jan-Henning

2017-06-22

Children with myeloid leukemia associated with Down syndrome (ML-DS) have superior outcome compared with non-DS patients, but suffer from higher constitutional cytotoxic drug susceptibility. We analyzed the outcome of 170 pediatric patients with ML-DS enrolled in the prospective, multicenter, open-label, nonrandomized ML-DS 2006 trial by Nordic Society for Pediatric Hematology and Oncology (NOPHO), Dutch Childhood Oncology Group (DCOG), and Acute Myeloid Leukemia-Berlin-Frankfurt-Münster (AML-BFM) study group. Compared with the historical control arm (reduced-intensity protocol for ML-DS patients from the AML-BFM 98 trial), treatment intensity was reduced by lowering the cumulative dose of etoposide (950 to 450 mg/m 2 ) and intrathecal central nervous system prophylaxis while omitting maintenance therapy. Still, 5-year overall survival (89% ± 3% vs 90% ± 4%; P log-rank = .64), event-free survival (EFS; 87% ± 3% vs 89% ± 4%; P log-rank = .71), and cumulative incidence of relapse/nonresponse (CIR/NR; 6% ± 3% vs 6% ± 2%; P Gray = .03) did not significantly differ between the ML-DS 2006 trial and the historical control arm. Poor early treatment response (5-year EFS, 58% ± 16% vs 88% ± 3%; P log rank = .0008) and gain of chromosome 8 (CIR/NR, 16% ± 7% vs 3% ± 2%, P Gray = .02; 5-year EFS, 73% ± 8% vs 91% ± 4%, P log rank = .018) were identified as independent prognostic factors predicting a worse EFS. Five of 7 relapsed patients (71%) with cytogenetic data had trisomy 8. Our study reveals prognostic markers for children with ML-DS and illustrates that reducing therapy did not impair excellent outcome. The trial was registered at EudraCT as #2007-006219-2. © 2017 by The American Society of Hematology.

Multi-bounce laser-based sails

NASA Astrophysics Data System (ADS)

Metzger, Robert A.; Landis, Geoffrey

2001-02-01

A laser-based lightsail craft is proposed in which the laser beam is operated in a multi-bounce mode, such that after first striking the lightsail, the beam is reflected back to a source reflector where it is again directed to the lightsail. Recent developments in nearly ideal reflectors permit more than 1000 bounces, which reduce the laser power requirements by a factor of 1000 as compared to conventional laser-based lightsail proposals. Using the multi-bounce lightsail approach coupled with lasers operating in the power range of 100 MW to 1 GW, the details of a mission to Mars requiring only a sub-100 day transit, and an orbital transfer vehicle designed to transport cargo between Phobos and Deimos are examined. .

Bystander killing effect of DS-8201a, a novel anti-human epidermal growth factor receptor 2 antibody-drug conjugate, in tumors with human epidermal growth factor receptor 2 heterogeneity.

PubMed

Ogitani, Yusuke; Hagihara, Katsunobu; Oitate, Masataka; Naito, Hiroyuki; Agatsuma, Toshinori

2016-07-01

Antibody-drug conjugates deliver anticancer agents selectively and efficiently to tumor tissue and have significant antitumor efficacy with a wide therapeutic window. DS-8201a is a human epidermal growth factor receptor 2 (HER2)-targeting antibody-drug conjugate prepared using a novel linker-payload system with a potent topoisomerase I inhibitor, exatecan derivative (DX-8951 derivative, DXd). It was effective against trastuzumab emtansine (T-DM1)-insensitive patient-derived xenograft models with both high and low HER2 expression. In this study, the bystander killing effect of DS-8201a was evaluated and compared with that of T-DM1. We confirmed that the payload of DS-8201a, DXd (1), was highly membrane-permeable whereas that of T-DM1, Lys-SMCC-DM1, had a low level of permeability. Under a coculture condition of HER2-positive KPL-4 cells and negative MDA-MB-468 cells in vitro, DS-8201a killed both cells, whereas T-DM1 and an antibody-drug conjugate with a low permeable payload, anti-HER2-DXd (2), did not. In vivo evaluation was carried out using mice inoculated with a mixture of HER2-positive NCI-N87 cells and HER2-negative MDA-MB-468-Luc cells by using an in vivo imaging system. In vivo, DS-8201a reduced the luciferase signal of the mice, indicating suppression of the MDA-MB-468-Luc population; however, T-DM1 and anti-HER2-DXd (2) did not. Furthermore, it was confirmed that DS-8201a was not effective against MDA-MB-468-Luc tumors inoculated at the opposite side of the NCI-N87 tumor, suggesting that the bystander killing effect of DS-8201a is observed only in cells neighboring HER2-positive cells, indicating low concern in terms of systemic toxicity. These results indicated that DS-8201a has a potent bystander effect due to a highly membrane-permeable payload and is beneficial in treating tumors with HER2 heterogeneity that are unresponsive to T-DM1. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer

ESAM: Endocrine inspired Sensor Activation Mechanism for multi-target tracking in WSNs

NASA Astrophysics Data System (ADS)

Adil Mahdi, Omar; Wahab, Ainuddin Wahid Abdul; Idris, Mohd Yamani Idna; Znaid, Ammar Abu; Khan, Suleman; Al-Mayouf, Yusor Rafid Bahar

2016-10-01

Target tracking is a significant application of wireless sensor networks (WSNs) in which deployment of self-organizing and energy efficient algorithms is required. The tracking accuracy increases as more sensor nodes are activated around the target but more energy is consumed. Thus, in this study, we focus on limiting the number of sensors by forming an ad-hoc network that operates autonomously. This will reduce the energy consumption and prolong the sensor network lifetime. In this paper, we propose a fully distributed algorithm, an Endocrine inspired Sensor Activation Mechanism for multi target-tracking (ESAM) which reflecting the properties of real life sensor activation system based on the information circulating principle in the endocrine system of the human body. Sensor nodes in our network are secreting different hormones according to certain rules. The hormone level enables the nodes to regulate an efficient sleep and wake up cycle of nodes to reduce the energy consumption. It is evident from the simulation results that the proposed ESAM in autonomous sensor network exhibits a stable performance without the need of commands from a central controller. Moreover, the proposed ESAM generates more efficient and persistent results as compared to other algorithms for tracking an invading object.

Simulated Lidar Images of Human Pose using a 3DS Max Virtual Laboratory

DTIC Science & Technology

2015-12-01

developed in Autodesk 3DS Max, with an animated, biofidelic 3D human mesh biped character ( avatar ) as the subject. The biped animation modifies the digital...character ( avatar ) as the subject. The biped animation modifies the digital human model through a time sequence of motion capture data representing an...AFB. Mr. Isiah Davenport from Infoscitex Corp developed the method for creating the biofidelic avatars from laboratory data and 3DS Max code for

A Mw 6.3 earthquake scenario in the city of Nice (southeast France): ground motion simulations

NASA Astrophysics Data System (ADS)

Salichon, Jérome; Kohrs-Sansorny, Carine; Bertrand, Etienne; Courboulex, Françoise

2010-07-01

The southern Alps-Ligurian basin junction is one of the most seismically active zone of the western Europe. A constant microseismicity and moderate size events (3.5 < M < 5) are regularly recorded. The last reported historical event took place in February 1887 and reached an estimated magnitude between 6 and 6.5, causing human losses and extensive damages (intensity X, Medvedev-Sponheuer-Karnik). Such an event, occurring nowadays, could have critical consequences given the high density of population living on the French and Italian Riviera. We study the case of an offshore Mw 6.3 earthquake located at the place where two moderate size events (Mw 4.5) occurred recently and where a morphotectonic feature has been detected by a bathymetric survey. We used a stochastic empirical Green’s functions (EGFs) summation method to produce a population of realistic accelerograms on rock and soil sites in the city of Nice. The ground motion simulations are calibrated on a rock site with a set of ground motion prediction equations (GMPEs) in order to estimate a reasonable stress-drop ratio between the February 25th, 2001, Mw 4.5, event taken as an EGF and the target earthquake. Our results show that the combination of the GMPEs and EGF techniques is an interesting tool for site-specific strong ground motion estimation.

Reliability and validity of DS-ADHD: A decision support system on attention deficit hyperactivity disorders.

PubMed

Chu, Kuo-Chung; Huang, Yu-Shu; Tseng, Chien-Fu; Huang, Hsin-Jou; Wang, Chih-Huan; Tai, Hsin-Yi

2017-03-01

The purpose of this study is to examine the reliability of the clinical use of the self-built decision support system, diagnosis-supported attention deficit hyperactivity disorder (DS-ADHD), in an effort to develop the DS-ADHD system, by probing into the development of indicating patterns of past screening support systems for ADHD. The study collected data based on 107 subjects, who were divided into two groups, non-ADHD and ADHD, based on the doctor's determination, using the DSM-IV diagnostic standards. The two groups then underwent Test of Variables of Attention (TOVA) and DS-ADHD testing. The survey and testing results underwent one-way ANOVA and split-half method statistical analysis, in order to further understand whether there were any differences between the DS-ADHD and the identification tools used in today's clinical trials. The results of the study are as follows: 1) The ROC area between the TOVA and the clinical identification rate is 0.787 (95% confidence interval: 0.701-0.872); 2) The ROC area between the DS-ADHD and the clinical identification rate is 0.867 (95% confidence interval: 0.801-0.933). The study results show that DS-ADHD has the characteristics of screening for ADHD, based on its reliability and validity. It does not display any statistical differences when compared with TOVA systems that are currently on the market. However, the system is more effective and the accuracy rate is better than TOVA. It is a good tool to screen ADHD not only in Chinese children, but also in western country. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Dramatically reduced surface expression of NK cell receptor KIR2DS3 is attributed to multiple residues throughout the molecule.

PubMed

VandenBussche, C J; Mulrooney, T J; Frazier, W R; Dakshanamurthy, S; Hurley, C K

2009-03-01

Using flow cytometry, fluorescent microscopy and examination of receptor glycosylation status, we demonstrate that an entire killer cell immunoglobulin-like receptor (KIR) locus (KIR2DS3)--assumed earlier to be surface expressed--appears to have little appreciable surface expression in transfected cells. This phenotype was noted for receptors encoded by three allelic variants including the common KIR2DS3*001 allele. Comparing the surface expression of KIR2DS3 with that of the better-studied KIR2DS1 molecule in two different cell lines, mutational analysis identified multiple polymorphic amino-acid residues that significantly alter the proportion of molecules present on the cell surface. A simultaneous substitution of five residues localized to the leader peptide (residues -18 and -7), second domain (residues 123 and 150) and transmembrane region (residue 234) was required to restore KIR2DS3 to the expression level of KIR2DS1. Corresponding simultaneous substitutions of KIR2DS1 to the KIR2DS3 residues resulted in a dramatically decreased surface expression. Molecular modeling was used to predict how these substitutions contribute to this phenotype. Alterations in receptor surface expression are likely to affect the balance of immune cell signaling impacting the characteristics of the response to pathogens or malignancy.

Baby de Sitter black holes and dS3/CFT2

NASA Astrophysics Data System (ADS)

de Buyl, Sophie; Detournay, Stéphane; Giribet, Gaston; Ng, Gim Seng

2014-02-01

Unlike three-dimensional Einstein gravity, three-dimensional massive gravity admits asymptotically de Sitter space (dS) black hole solutions. These black holes present interesting features and provide us with toy models to study the dS/CFT correspondence. A remarkable property of these black holes is that they are always in thermal equilibrium with the cosmological horizon of the space that hosts them. This invites us to study the thermodynamics of these solutions within the context of dS/CFT. We study the asymptotic symmetry group of the theory and find that it indeed coincides with the local two-dimensional conformal algebra. The charge algebra associated to the asymptotic Killing vectors consists of two copies of the Virasoro algebra with non-vanishing central extension. We compute the mass and angular momentum of the dS black holes and verify that a naive application of Cardy's formula exactly reproduces the entropy of both the black hole and the cosmological horizon. By adapting the holographic renormalization techniques to the case of dS space, we define the boundary stress tensor of the dual Euclidean conformal field theory.

Electrochemical study of the interaction between dsDNA and copper(I) using carbon paste and hanging mercury drop electrode.

PubMed

Stanić, Z; Girousi, S

2008-06-30

The interaction of copper(I) with double-stranded (ds) calf thymus DNA was studied in solution and at the electrode surface by means of transfer voltammetry using a carbon paste electrode (CPE) as working electrode in 0.2 M acetate buffer solution (pH 5.0). As a result of the interaction of Cu(I) between the base pairs of the dsDNA, the characteristic peaks of dsDNA, due to the oxidation of guanine and adenine, increased and after a certain concentration of Cu(I) a new peak at +1.37 V appeared, probably due to the formation of a purine-Cu(I) complex (dsDNA-Cu(I) complex). Accordingly, the interaction of copper(I) with calf thymus dsDNA was studied in solution as well as at the electrode surface using hanging mercury drop electrode (HMDE) by means of alternating current voltammetry (AC voltammetry) in 0.3 M NaCl and 50 mM sodium phosphate buffer (pH 8.5) as supporting electrolyte. Its interaction with DNA is shown to be time dependent. Significant changes in the characteristic peaks of dsDNA were observed after addition of higher concentration of Cu(I) to a solution containing dsDNA, as a result of the interaction between Cu(I) and dsDNA. All the experimental results indicate that Cu(I) can bind to DNA by electrostatic binding and form an association complex.

Intelligent multi-spectral IR image segmentation

NASA Astrophysics Data System (ADS)

Lu, Thomas; Luong, Andrew; Heim, Stephen; Patel, Maharshi; Chen, Kang; Chao, Tien-Hsin; Chow, Edward; Torres, Gilbert

2017-05-01

This article presents a neural network based multi-spectral image segmentation method. A neural network is trained on the selected features of both the objects and background in the longwave (LW) Infrared (IR) images. Multiple iterations of training are performed until the accuracy of the segmentation reaches satisfactory level. The segmentation boundary of the LW image is used to segment the midwave (MW) and shortwave (SW) IR images. A second neural network detects the local discontinuities and refines the accuracy of the local boundaries. This article compares the neural network based segmentation method to the Wavelet-threshold and Grab-Cut methods. Test results have shown increased accuracy and robustness of this segmentation scheme for multi-spectral IR images.

Complete genome sequence of Parvibaculum lavamentivorans type strain (DS-1(T)).

PubMed

Schleheck, David; Weiss, Michael; Pitluck, Sam; Bruce, David; Land, Miriam L; Han, Shunsheng; Saunders, Elizabeth; Tapia, Roxanne; Detter, Chris; Brettin, Thomas; Han, James; Woyke, Tanja; Goodwin, Lynne; Pennacchio, Len; Nolan, Matt; Cook, Alasdair M; Kjelleberg, Staffan; Thomas, Torsten

2011-12-31

Parvibaculum lavamentivorans DS-1(T) is the type species of the novel genus Parvibaculum in the novel family Rhodobiaceae (formerly Phyllobacteriaceae) of the order Rhizobiales of Alphaproteobacteria. Strain DS-1(T) is a non-pigmented, aerobic, heterotrophic bacterium and represents the first tier member of environmentally important bacterial communities that catalyze the complete degradation of synthetic laundry surfactants. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 3,914,745 bp long genome with its predicted 3,654 protein coding genes is the first completed genome sequence of the genus Parvibaculum, and the first genome sequence of a representative of the family Rhodobiaceae.

76 FR 10082 - 60-Day Notice of Proposed Information Collection: DS-157, Supplemental Nonimmigrant Visa Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-23

... Information Collection: DS-157, Supplemental Nonimmigrant Visa Application ACTION: Notice of request for...: Supplemental Nonimmigrant Visa Application. OMB Control Number: 1405-0134. Type of Request: Extension of a...). Form Number: DS-157. Respondents: Nonimmigrant visa applicants legally required to provide additional...

Deployment Design of Wireless Sensor Network for Simple Multi-Point Surveillance of a Moving Target

PubMed Central

Tsukamoto, Kazuya; Ueda, Hirofumi; Tamura, Hitomi; Kawahara, Kenji; Oie, Yuji

2009-01-01

In this paper, we focus on the problem of tracking a moving target in a wireless sensor network (WSN), in which the capability of each sensor is relatively limited, to construct large-scale WSNs at a reasonable cost. We first propose two simple multi-point surveillance schemes for a moving target in a WSN and demonstrate that one of the schemes can achieve high tracking probability with low power consumption. In addition, we examine the relationship between tracking probability and sensor density through simulations, and then derive an approximate expression representing the relationship. As the results, we present guidelines for sensor density, tracking probability, and the number of monitoring sensors that satisfy a variety of application demands. PMID:22412326

Common multiple dsRNAs are present in populations of the fungus Discula destructiva originating from widely separated geographic locations.

PubMed

Rong, R; Rao, S; Scott, S W; Tainter, F H

2001-02-01

DsRNAs were detected in 85/108 isolates of Discula destructiva, the cause of dogwood anthracnose, collected in South Carolina, Idaho, and Alabama. The eastern isolates contained a greater diversity of dsRNA than did Idaho isolates, but most isolates, irrespective of state of origin, contained two small bands (ca. 1.5-2.5 kb) with sequence homology indicated by Northern hybridization. Differences in the banding patterns suggest that genetic diversity of dsRNA in D. destructiva is generated rapidly and that D. destructiva can be simultaneously infected by multiple dsRNA viruses.

Commentary: PhDs in biochemistry education-5 years later.

PubMed

Offerdahl, Erika G; Momsen, Jennifer L; Osgood, Marcy

2014-01-01

In this commentary, the discussion of PhDs in biochemistry education research is expanded to explore a number of diverse pathways leading to a competitive research program in biochemistry education research. © 2013 by The International Union of Biochemistry and Molecular Biology.

Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants

PubMed Central

Moreira-Filho, Carlos Alberto; Bando, Silvia Yumi; Bertonha, Fernanda Bernardi; Silva, Filipi Nascimento; da Fontoura Costa, Luciano; Ferreira, Leandro Rodrigues; Furlanetto, Glaucio; Chacur, Paulo; Zerbini, Maria Claudia Nogueira; Carneiro-Sampaio, Magda

2016-01-01

Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the “canonical” way of thymus functioning. Conversely, DS networks represent a “non-canonical” way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. PMID:26848775

Distribution of Unlinked Transpositions of a Ds Element from a T-DNA Locus on Tomato Chromosome 4

PubMed Central

Briza, J.; Carroll, B. J.; Klimyuk, V. I.; Thomas, C. M.; Jones, D. A.; Jones, JDG.

1995-01-01

In maize, receptor sites for unlinked transpositions of Activator (Ac) elements are not distributed randomly. To test whether the same is true in tomato, the receptor sites for a Dissociation (Ds) element derived from Ac, were mapped for 26 transpositions unlinked to a donor T-DNA locus on chromosome 4. Four independent transposed Dss mapped to sites on chromosome 4 genetically unlinked to the donor T-DNA, consistent with a preference for transposition to unlinked sites on the same chromosome as opposed to sites on other chromosomes. There was little preference among the nondonor chromosomes, except perhaps for chromosome 2, which carried seven transposed Dss, but these could not be proven to be independent. However, these data, when combined with those from other studies in tomato examining the distribution of transposed Acs or Dss among nondonor chromosomes, suggest there may be absolute preferences for transposition irrespective of the chromosomal location of the donor site. If true, transposition to nondonor chromosomes in tomato would differ from that in maize, where the preference seems to be determined by the spatial arrangement of chromosomes in the interphase nucleus. The tomato lines carrying Ds elements at known locations are available for targeted transposon tagging experiments. PMID:8536985

Determination of the radius of comet 19P/Borrelly in support of the NMP DS1 Flyby

NASA Astrophysics Data System (ADS)