Bioluminescence methodology for the detection of protein-protein interactions within the voltage-gated sodium channel macromolecular complex.

PubMed

Shavkunov, Alexander; Panova, Neli; Prasai, Anesh; Veselenak, Ron; Bourne, Nigel; Stoilova-McPhie, Svetla; Laezza, Fernanda

2012-04-01

Protein-protein interactions are critical molecular determinants of ion channel function and emerging targets for pharmacological interventions. Yet, current methodologies for the rapid detection of ion channel macromolecular complexes are still lacking. In this study we have adapted a split-luciferase complementation assay (LCA) for detecting the assembly of the voltage-gated Na+ (Nav) channel C-tail and the intracellular fibroblast growth factor 14 (FGF14), a functionally relevant component of the Nav channelosome that controls gating and targeting of Nav channels through direct interaction with the channel C-tail. In the LCA, two complementary N-terminus and C-terminus fragments of the firefly luciferase were fused, respectively, to a chimera of the CD4 transmembrane segment and the C-tail of Nav1.6 channel (CD4-Nav1.6-NLuc) or FGF14 (CLuc-FGF14). Co-expression of CLuc-FGF14 and CD4-Nav1.6-NLuc in live cells led to a robust assembly of the FGF14:Nav1.6 C-tail complex, which was attenuated by introducing single-point mutations at the predicted FGF14:Nav channel interface. To evaluate the dynamic regulation of the FGF14:Nav1.6 C-tail complex by signaling pathways, we investigated the effect of kinase inhibitors on the complex formation. Through a platform of counter screenings, we show that the p38/MAPK inhibitor, PD169316, and the IκB kinase inhibitor, BAY 11-7082, reduce the FGF14:Nav1.6 C-tail complementation, highlighting a potential role of the p38MAPK and the IκB/NFκB pathways in controlling neuronal excitability through protein-protein interactions. We envision the methodology presented here as a new valuable tool to allow functional evaluations of protein-channel complexes toward probe development and drug discovery targeting ion channels implicated in human disorders.

State/federal interaction of LANDSAT system and related technical assistance

NASA Technical Reports Server (NTRS)

Tesser, P. A.

1981-01-01

The history of state involvement in LANDSAT systems planning and related efforts is described. Currently 16 states have visual LANDSAT capabilities and 10 others are planning on developing such capabilities. The federal government's future plans for the LANDSAT system, the impacts of recent budget decisions on the systems, and the FY 82 budget process are examined.

Teacher-Student Dialogue during One-to-One Interactions in a Post-16 Mathematics Classroom

ERIC Educational Resources Information Center

Grandi, Clarissa

2013-01-01

Current reforms in mathematics education place dialogue at the heart of the development of conceptual understanding. Underlying these ideas is strong criticism of transmissive teaching styles, often referred to as "teaching by telling" However, there is little in terms of specific guidance for teachers about how best to achieve these…

Measurement of the neutrino-oxygen neutral-current interaction cross section by observing nuclear deexcitation γ rays

NASA Astrophysics Data System (ADS)

Abe, K.; Adam, J.; Aihara, H.; Akiri, T.; Andreopoulos, C.; Aoki, S.; Ariga, A.; Ariga, T.; Assylbekov, S.; Autiero, D.; Barbi, M.; Barker, G. J.; Barr, G.; Bass, M.; Batkiewicz, M.; Bay, F.; Bentham, S. W.; Berardi, V.; Berger, B. E.; Berkman, S.; Bertram, I.; Bhadra, S.; Blaszczyk, F. d. M.; Blondel, A.; Bojechko, C.; Bordoni, S.; Boyd, S. B.; Brailsford, D.; Bravar, A.; Bronner, C.; Buchanan, N.; Calland, R. G.; Caravaca Rodríguez, J.; Cartwright, S. L.; Castillo, R.; Catanesi, M. G.; Cervera, A.; Cherdack, D.; Christodoulou, G.; Clifton, A.; Coleman, J.; Coleman, S. J.; Collazuol, G.; Connolly, K.; Cremonesi, L.; Dabrowska, A.; Danko, I.; Das, R.; Davis, S.; de Perio, P.; De Rosa, G.; Dealtry, T.; Dennis, S. R.; Densham, C.; Dewhurst, D.; Di Lodovico, F.; Di Luise, S.; Drapier, O.; Duboyski, T.; Duffy, K.; Dufour, F.; Dumarchez, J.; Dytman, S.; Dziewiecki, M.; Emery-Schrenk, S.; Ereditato, A.; Escudero, L.; Finch, A. J.; Fiorentini Aguirre, G. A.; Friend, M.; Fujii, Y.; Fukuda, Y.; Furmanski, A. P.; Galymov, V.; Gaudin, A.; Giffin, S.; Giganti, C.; Gilje, K.; Goeldi, D.; Golan, T.; Gomez-Cadenas, J. J.; Gonin, M.; Grant, N.; Gudin, D.; Hadley, D. R.; Haegel, L.; Haesler, A.; Haigh, M. D.; Hamilton, P.; Hansen, D.; Hara, T.; Hartz, M.; Hasegawa, T.; Hastings, N. C.; Hayato, Y.; Hearty, C.; Helmer, R. L.; Hierholzer, M.; Hignight, J.; Hillairet, A.; Himmel, A.; Hiraki, T.; Hirota, S.; Holeczek, J.; Horikawa, S.; Huang, K.; Ichikawa, A. K.; Ieki, K.; Ieva, M.; Ikeda, M.; Imber, J.; Insler, J.; Irvine, T. J.; Ishida, T.; Ishii, T.; Ives, S. J.; Iwai, E.; Iwamoto, K.; Iyogi, K.; Izmaylov, A.; Jacob, A.; Jamieson, B.; Johnson, R. A.; Johnson, S.; Jo, J. H.; Jonsson, P.; Jung, C. K.; Kabirnezhad, M.; Kaboth, A. C.; Kajita, T.; Kakuno, H.; Kameda, J.; Kanazawa, Y.; Karlen, D.; Karpikov, I.; Katori, T.; Kearns, E.; Khabibullin, M.; Khotjantsev, A.; Kielczewska, D.; Kikawa, T.; Kilinski, A.; Kim, J.; King, S.; Kisiel, J.; Kitching, P.; Kobayashi, T.; Koch, L.; Kolaceke, A.; Konaka, A.; Kormos, L. L.; Korzenev, A.; Koseki, K.; Koshio, Y.; Kreslo, I.; Kropp, W.; Kubo, H.; Kudenko, Y.; Kumaratunga, S.; Kurjata, R.; Kutter, T.; Lagoda, J.; Laihem, K.; Lamont, I.; Larkin, E.; Laveder, M.; Lawe, M.; Lazos, M.; Lee, K. P.; Licciardi, C.; Lindner, T.; Lister, C.; Litchfield, R. P.; Longhin, A.; Ludovici, L.; Macaire, M.; Magaletti, L.; Mahn, K.; Malek, M.; Manly, S.; Marino, A. D.; Marteau, J.; Martin, J. F.; Martynenko, S.; Maruyama, T.; Marzec, J.; Mathie, E. L.; Matveev, V.; Mavrokoridis, K.; Mazzucato, E.; McCarthy, M.; McCauley, N.; McFarland, K. S.; McGrew, C.; Mefodiev, A.; Metelko, C.; Mezzetto, M.; Mijakowski, P.; Miller, C. A.; Minamino, A.; Mineev, O.; Mine, S.; Missert, A.; Miura, M.; Monfregola, L.; Moriyama, S.; Mueller, Th. A.; Murakami, A.; Murdoch, M.; Murphy, S.; Myslik, J.; Nagasaki, T.; Nakadaira, T.; Nakahata, M.; Nakai, T.; Nakamura, K.; Nakayama, S.; Nakaya, T.; Nakayoshi, K.; Nantais, C.; Naples, D.; Nielsen, C.; Nirkko, M.; Nishikawa, K.; Nishimura, Y.; Nowak, J.; O'Keeffe, H. M.; Ohta, R.; Okumura, K.; Okusawa, T.; Oryszczak, W.; Oser, S. M.; Ovsyannikova, T.; Owen, R. A.; Oyama, Y.; Palladino, V.; Palomino, J. L.; Paolone, V.; Payne, D.; Pearce, G. F.; Perevozchikov, O.; Perkin, J. D.; Petrov, Y.; Pickard, L.; Pinzon Guerra, E. S.; Pistillo, C.; Plonski, P.; Poplawska, E.; Popov, B.; Posiadala-Zezula, M.; Poutissou, J.-M.; Poutissou, R.; Przewlocki, P.; Quilain, B.; Radicioni, E.; Ratoff, P. N.; Ravonel, M.; Rayner, M. A. M.; Redij, A.; Reeves, M.; Reinherz-Aronis, E.; Riccio, C.; Retiere, F.; Robert, A.; Rodrigues, P. A.; Rojas, P.; Rondio, E.; Roth, S.; Rubbia, A.; Ruterbories, D.; Sacco, R.; Sakashita, K.; Sánchez, F.; Sato, F.; Scantamburlo, E.; Scholberg, K.; Schoppmann, S.; Schwehr, J.; Scott, M.; Seiya, Y.; Sekiguchi, T.; Sekiya, H.; Sgalaberna, D.; Shaker, F.; Shiozawa, M.; Short, S.; Shustrov, Y.; Sinclair, P.; Smith, B.; Smith, R. J.; Smy, M.; Sobczyk, J. T.; Sobel, H.; Sorel, M.; Southwell, L.; Stamoulis, P.; Steinmann, J.; Still, B.; Suda, Y.; Suzuki, A.; Suzuki, K.; Suzuki, S. Y.; Suzuki, Y.; Szeglowski, T.; Tacik, R.; Tada, M.; Takahashi, S.; Takeda, A.; Takeuchi, Y.; Tanaka, H. K.; Tanaka, H. A.; Tanaka, M. M.; Taylor, I. J.; Terhorst, D.; Terri, R.; Thompson, L. F.; Thorley, A.; Tobayama, S.; Toki, W.; Tomura, T.; Totsuka, Y.; Touramanis, C.; Tsukamoto, T.; Tzanov, M.; Uchida, Y.; Ueno, K.; Vacheret, A.; Vagins, M.; Vasseur, G.; Wachala, T.; Waldron, A. V.; Walter, C. W.; Wark, D.; Wascko, M. O.; Weber, A.; Wendell, R.; Wilkes, R. J.; Wilking, M. J.; Wilkinson, C.; Williamson, Z.; Wilson, J. R.; Wilson, R. J.; Wongjirad, T.; Yamada, Y.; Yamamoto, K.; Yanagisawa, C.; Yano, T.; Yen, S.; Yershov, N.; Yokoyama, M.; Yuan, T.; Yu, M.; Zalewska, A.; Zalipska, J.; Zambelli, L.; Zaremba, K.; Ziembicki, M.; Zimmerman, E. D.; Zito, M.; Żmuda, J.; T2K Collaboration

2014-10-01

We report the first measurement of the neutrino-oxygen neutral-current quasielastic (NCQE) cross section. It is obtained by observing nuclear deexcitation γ rays which follow neutrino-oxygen interactions at the Super-Kamiokande water Cherenkov detector. We use T2K data corresponding to 3.01 ×1 020 protons on target. By selecting only events during the T2K beam window and with well-reconstructed vertices in the fiducial volume, the large background rate from natural radioactivity is dramatically reduced. We observe 43 events in the 4-30 MeV reconstructed energy window, compared with an expectation of 51.0, which includes an estimated 16.2 background events. The background is primarily nonquasielastic neutral-current interactions and has only 1.2 events from natural radioactivity. The flux-averaged NCQE cross section we measure is 1.55 ×1 0-38 cm2 with a 68% confidence interval of (1.22 ,2.20 )×1 0-38 cm2 at a median neutrino energy of 630 MeV, compared with the theoretical prediction of 2.01 ×1 0-38 cm2 .

Toxoplasma aldolase is required for metabolism but dispensable for host-cell invasion.

PubMed

Shen, Bang; Sibley, L David

2014-03-04

Gliding motility and host-cell invasion by apicomplexan parasites depend on cell-surface adhesins that are translocated via an actin-myosin motor beneath the membrane. The current model posits that fructose-1,6-bisphosphate aldolase (ALD) provides a critical link between the cytoplasmic tails of transmembrane adhesins and the actin-myosin motor. Here we tested this model using the Toxoplasma gondii apical membrane protein 1 (TgAMA1), which binds to aldolase in vitro. TgAMA1 cytoplasmic tail mutations that disrupt ALD binding in vitro showed no correlation with host-cell invasion, indicating this interaction is not essential. Furthermore, ALD-depleted parasites were impaired when grown in glucose, yet they showed normal gliding and invasion in glucose-free medium. Depletion of ALD in the presence of glucose led to accumulation of fructose-1,6-bisphosphate, which has been associated with toxicity in other systems. Finally, TgALD knockout parasites and an ALD mutant that specifically disrupts adhesin binding in vitro also supported normal invasion when cultured in glucose-free medium. Taken together, these results suggest that ALD is primarily important for energy metabolism rather than interacting with microneme adhesins, challenging the current model for apicomplexan motility and invasion.

Effects of Prenatal Tobacco, Alcohol and Marijuana Exposure on Processing Speed, Visual-Motor Coordination, and Interhemispheric Transfer

PubMed Central

Willford, Jennifer A.; Chandler, Lynette S.; Goldschmidt, Lidush; Day, Nancy L.

2010-01-01

Deficits in motor control are often reported in children with prenatal alcohol exposure (PAE). Less is known about the effects of prenatal tobacco exposure (PTE) and prenatal marijuana exposure (PME) on motor coordination, and previous studies have not considered whether PTE, PAE, and PME interact to affect motor control. This study investigated the effects of PTE, PAE, and PME as well as current drug use on speed of processing, visual-motor coordination, and interhemispheric transfer in 16-year-old adolescents. Data were collected as part of the Maternal Health Practices and Child Development Project. Adolescents (age 16, n=320) participating in a longitudinal study of the effects of prenatal substance exposure on developmental outcomes were evaluated in this study. The computerized Bimanual Coordination Test (BCT) was used to assess each domain of function. Other important variables, such as demographics, home environment, and psychological characteristics of the mother and adolescent were also considered in the analyses. There were significant and independent effects of PTE, PAE, and PME on processing speed and interhemispheric transfer of information. PTEand PME were associated with deficits in visual motor coordination. There were no interactions between PAE, PTE, and PME. Current tobacco use predicted deficits in speed of processing. Current alcohol and marijuana use by the offspring were not associated with any measures of performance on the BCT. PMID:20600845

Mother-child interactions in depressed children and children at high risk and low risk for future depression.

PubMed

Dietz, Laura J; Birmaher, Boris; Williamson, Douglas E; Silk, Jennifer S; Dahl, Ronald E; Axelson, David A; Ehmann, Mary; Ryan, Neal D

2008-05-01

To compare mother-child interactions and parenting styles in families of children with major depressive disorder, youths at high risk for depression, and healthy controls. Currently depressed (n = 43), high-risk (n = 28), and healthy control (n = 41) youths and their mothers engaged in a standardized videotaped problem-solving interaction. Measures of affect and behavior for both mothers and children were obtained, in addition to global measures of parenting. Depressed children demonstrated more negativity and less positivity in dyadic interactions than did children at high risk and control children. Mothers of depressed children were more disengaged than control mothers. Exploratory repeated-measures analyses in a subgroup of depressed children (n = 16) suggested mother-child interactions do not significantly change when children recover from depression. Children at high risk demonstrated less positivity in dyadic interactions than did controls. Mothers with a history of major depressive disorder and mothers with higher current depressive symptoms demonstrated patterns of disengagement and low control in interactions with children. Mother-child interactions in depressed youths are marked by maternal disengagement and low child positivity that may not improve when children recover. The bidirectional effects of maternal disengagement and low levels of child positivity may precede onset of major depressive disorder in children and serve as risk factors for recurrent depression in youths.

The Ca{sup 2+} channel TRPML3 specifically interacts with the mammalian ATG8 homologue GATE16 to regulate autophagy

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

Choi, Suzy; Kim, Hyun Jin, E-mail: kimhyunjin@skku.edu

2014-01-03

Highlights: •Split-ubiquitin MY2H screen identified GATE16 as an interacting protein of TRPML3. •TRPML3 specifically binds to a mammalian ATG8 homologue GATE16, not to LC3B. •The interaction of TRPML3 with GATE16 facilitates autophagosome formation. •GATE16 is expressed in both autophagosome and extra-autophagosomal compartments. -- Abstract: TRPML3 is a Ca{sup 2+} permeable cation channel expressed in multiple intracellular compartments. Although TRPML3 is implicated in autophagy, how TRPML3 can regulate autophagy is not understood. To search interacting proteins with TRPML3 in autophagy, we performed split-ubiquitin membrane yeast two-hybrid (MY2H) screening with TRPML3-loop as a bait and identified GATE16, a mammalian ATG8 homologue. GSTmore » pull-down assay revealed that TRPML3 and TRPML3-loop specifically bind to GATE16, not to LC3B. Co-immunoprecipitation (co-IP) experiments showed that TRPML3 and TRPML3-loop pull down only the lipidated form of GATE16, indicating that the interaction occurs exclusively at the organellar membrane. The interaction of TRPML3 with GATE16 and GATE16-positive vesicle formation were increased in starvation induced autophagy, suggesting that the interaction facilitates the function of GATE16 in autophagosome formation. However, GATE16 was not required for TRPML3 trafficking to autophagosomes. Experiments using dominant-negative (DN) TRPML3(D458K) showed that GATE16 is localized not only in autophagosomes but also in extra-autophagosomal compartments, by contrast with LC3B. Since GATE16 acts at a later stage of the autophagosome biogenesis, our results suggest that TRPML3 plays a role in autophagosome maturation through the interaction with GATE16, by providing Ca{sup 2+} in the fusion process.« less

Cannabis use in early adolescence is associated with higher negative schizotypy in females.

PubMed

Albertella, L; Le Pelley, M E; Copeland, J

2017-09-01

The current study examined the relationship between early onset cannabis use (before age 16) and different schizotypy dimensions, and whether gender moderates these associations. Participants were 162 cannabis users, aged 15-24 years, who completed an online assessment examining alcohol and other drug use, psychological distress, and schizotypy. Participants were divided according to whether or not they had started using cannabis before the age of 16 (early onset=47; later onset=115) and gender (males=66; females=96). The interaction between gender and onset group was significantly associated with the dimension of introvertive anhedonia. Follow-up analyses showed that early onset cannabis use was associated with higher levels of introvertive anhedonia in females only. The current findings suggest that gender is an important moderator in the association between early onset cannabis use, schizotypy, and possibly, psychosis risk. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Plasma Interactions with Spacecraft. Volume 2, NASCAP-2K Scientific Documentation for Version 4.1

DTIC Science & Technology

2011-04-15

E expn E m2 e EF (2) Double Maxwellian                      2 2 221 1 11 E expn E m2 eE expn E...m2 e EF (3) Fontheim (electrons only) This distribution is used to model auroral electrons.      LUpower 2 gauss o gaussmax EEHEEHE EE ...to secondary electron current. ee emitted secondary current due to electron impact Y primary electron current  (16) A typical curve is shown in

Expression of CXCR6 on CD8(+) T cells was up-regulated in allograft rejection.

PubMed

Jiang, Xiaofeng; Sun, Wenyu; Zhu, Lei; Guo, Dawei; Jiang, Honglei; Ma, Dongyan; Jin, Junzhe; Zhao, Yu; Liang, Jian

2010-02-01

CXCL16/SR-PSOX is a novel transmembrane-type chemokine, which was also identified as a novel scavenger receptor for oxidized low density lipoprotein. Its receptor CXCR6 expresses on activated CD8(+) T cells, type 1-polarized CD4(+), and constitutively expresses on NKT cells. Moreover, it has been shown that CXCL16 accumulated activated CD8(+) T cells to sites of inflammation. To date, the effect of CXCL16 (SR-PSOX)/CXCR6 on CD8(+) T cells and its role in allograft rejection/acceptance are not well understood. In the current study, we show that rejected allografts showed higher expressions of CXCR6 and CXCL16. More importantly, expression of CXCR6 on CD8(+) T cells was also up-regulated by rejection. However, the blockade of CXCL16(SR-PSOX)/CXCR6 interaction could not inhibit cytotoxic activity of CD8(+) T cells, and therefore, could not prolong the cardiac graft survival time. Copyright 2009 Elsevier B.V. All rights reserved.

Visualization of fluid dynamics at NASA Ames

NASA Technical Reports Server (NTRS)

Watson, Val

1989-01-01

The hardware and software currently used for visualization of fluid dynamics at NASA Ames is described. The software includes programs to create scenes (for example particle traces representing the flow over an aircraft), programs to interactively view the scenes, and programs to control the creation of video tapes and 16mm movies. The hardware includes high performance graphics workstations, a high speed network, digital video equipment, and film recorders.

Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions.

PubMed

Schäfer, Georgia; Graham, Lisa M; Lang, Dirk M; Blumenthal, Melissa J; Bergant Marušič, Martina; Katz, Arieh A

2017-08-15

Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface events preceding oncogenic HPV internalization are poorly understood. We herein describe the identification of surface-expressed vimentin as a novel molecule not previously implicated in the infectious internalization of HPV16. Contrary to our expectations, vimentin was found to act not as a receptor but rather as a restriction factor dampening the initial steps of HPV16 infection. These results importantly contribute to our current understanding of the molecular events during the infectious internalization of HPV16 and open a new direction in the development of alternative drugs to prevent HPV infection. Copyright © 2017 Schäfer et al.

N‐glycosylation by N‐acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis

PubMed Central

Cui, Jian; Huang, Wan; Wu, Bo; Jin, Jin; Jing, Lin; Shi, Wen‐Pu; Liu, Zhen‐Yu; Yuan, Lin; Luo, Dan; Li, Ling

2018-01-01

Abstract While the importance of protein N‐glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N‐acetylglucosaminyltransferase V (GnT‐V) regulates cancer processes remain largely unknown. In the current study, we report that GnT‐V‐mediated N‐glycosylation of CD147/basigin, a tumor‐associated glycoprotein that carries β1,6‐N‐acetylglucosamine (β1,6‐GlcNAc) glycans, is upregulated during TGF‐β1‐induced epithelial‐to‐mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of β1,6‐GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin β1. These results reveal that β1,6‐branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT‐V expression and that inhibition of GnT‐V‐mediated N‐glycosylation suppressed PI3K signaling. In summary, β1,6‐branched N‐glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:29431199

Interaction of atorvastatin with the human glial transporter SLC16A1.

PubMed

Sasaki, Shotaro; Futagi, Yuya; Ideno, Masaya; Kobayashi, Masaki; Narumi, Katsuya; Furugen, Ayako; Iseki, Ken

2016-10-05

Solute carrier (SLC) 16A1 is a pH-dependent carrier of 5-oxoproline, a derivative of the amino acid. SLC16A1 interacts with carboxylate group-containing substrates, which are also present in atorvastatin, and might be the reason for its ability to interact with atorvastatin. Does atorvastatin interact with the carrier? Does it also interact with the carrier via the substrate recognition site? This study was carried out to answer these questions. Polymerase chain reaction was used to determine the expression of SLC16A1 in normal human astrocytes. We induced SLC16A1 expression in a mammalian cell line and in Xenopus laevis oocytes. We used [(3)H] 5-oxoproline for direct measurement of SLC16A1-specific transport activity. SLC16A1 was clearly observed in normal human astrocytes. 3-Hydroxy-3-methyl-glutaryl-CoA reductase inhibitors inhibited the SLC16A1-specific transport of 5-oxoproline. Atorvastatin was the most potent inhibitor, with an inhibition constant of 40μM. The drug was a non-competitive inhibitor of SLC16A1. In the present study, we showed non-competitive inhibition of SLC16A1-specific transport activity by atorvastatin. However, the affinity between the drug and the carrier was extremely low. Therefore, the interaction of atorvastatin with SLC16A1 is unlikely to be a problem in clinical practice. Copyright © 2016. Published by Elsevier B.V.

Defining the interaction of human soluble lectin ZG16p and mycobacterial phosphatidylinositol mannosides

PubMed Central

Ikeda, Akemi; Kojima-Aikawa, Kyoko; Taniguchi, Naoyuki; Varón Silva, Daniel; Feizi, Ten; Seeberger, Peter H.; Yamaguchi, Yoshiki

2018-01-01

ZG16p is a soluble mammalian lectin that interacts with mannose and heparan sulfate. Here we describe detailed analyses of the interactions of human ZG16p with mycobacterial phosphatidylinositol mannosides (PIMs), using glycan microarray and NMR. Pathogen-related glycan microarray analysis identified phosphatidylinositol mono- and di-mannosides (PIM1 and PIM2) as novel ligand candidates of ZG16p. Saturation Transfer Difference (STD) NMR and transferred NOE experiments with chemically synthesized PIM glycans indicate that PIMs preferentially interacts with ZG16p using the mannose residues. Binding site of PIMs is identified by chemical shift perturbation experiments using uniformly 15N-labeled ZG16p. NMR results with docking simulations suggest a binding mode of ZG16p and PIM glycan, which would help to consider the physiological role of ZG16p. PMID:25919894

Domain Interaction Studies of Herpes Simplex Virus 1 Tegument Protein UL16 Reveal Its Interaction with Mitochondria

PubMed Central

Chadha, Pooja; Sarfo, Akua; Zhang, Dan; Abraham, Thomas; Carmichael, Jillian

2016-01-01

ABSTRACT The UL16 tegument protein of herpes simplex virus 1 (HSV-1) is conserved among all herpesviruses and plays many roles during replication. This protein has an N-terminal domain (NTD) that has been shown to bind to several viral proteins, including UL11, VP22, and glycoprotein E, and these interactions are negatively regulated by a C-terminal domain (CTD). Thus, in pairwise transfections, UL16 binding is enabled only when the CTD is absent or altered. Based on these results, we hypothesized that direct interactions occur between the NTD and the CTD. Here we report that the separated and coexpressed functional domains of UL16 are mutually responsive to each other in transfected cells and form complexes that are stable enough to be captured in coimmunoprecipitation assays. Moreover, we found that the CTD can associate with itself. To our surprise, the CTD was also found to contain a novel and intrinsic ability to localize to specific spots on mitochondria in transfected cells. Subsequent analyses of HSV-infected cells by immunogold electron microscopy and live-cell confocal imaging revealed a population of UL16 that does not merely accumulate on mitochondria but in fact makes dynamic contacts with these organelles in a time-dependent manner. These findings suggest that the domain interactions of UL16 serve to regulate not just the interaction of this tegument protein with its viral binding partners but also its interactions with mitochondria. The purpose of this novel interaction remains to be determined. IMPORTANCE The HSV-1-encoded tegument protein UL16 is involved in multiple events of the virus replication cycle, ranging from virus assembly to cell-cell spread of the virus, and hence it can serve as an important drug target. Unfortunately, a lack of both structural and functional information limits our understanding of this protein. The discovery of domain interactions within UL16 and the novel ability of UL16 to interact with mitochondria in HSV-infected cells lays a foundational framework for future investigations aimed at deciphering the structure and function of not just UL16 of HSV-1 but also its homologs in other herpesviruses. PMID:27847362

Bell pair creation in current of Kondo-correlated dot

NASA Astrophysics Data System (ADS)

Sakano, Rui; Oguri, Akira; Nishikawa, Yunori; Abe, Eisuke

Recently, local-Fermi-liquid properties in non-linear currents and shot noises through the Kondo dot have been investigated both theoretically and experimentally. We suggest a new entangled-electron-pair generator utilizing mechanism of quasiparticle-pair creation which has been observed as enhancement of shot noise in the quantum dot. Using the renormalized perturbation theory for an orbital-degenerate impurity Anderson model and the full counting statistics, we calculate the Clauser-Horne-Shimony-Holt type Bell's correlator for currents through correlated two different channels of a Kondo correlated dot. It is shown that residual exchange-interactions of the local-Fermi-liquid create spin-entangled quasiparticle-pairs in nonlinear current and this results in violation of the Bell's inequality. This work was partially supported by JSPS KAKENHI Grant Numbers JP26220711, JP26400319, JP15K05181 and JP16K17723.

Interaction of cetyltrimethylammonium bromide and its gemini homologue bis(cetyldimethylammonium)butane dibromide with xanthine oxidase.

PubMed

Mir, Mohammad Amin; Khan, Javed Masood; Khan, Rizwan Hasan; Dar, Aijaz Ahmad; Rather, Ghulam Mohammad

2012-05-17

The interaction of xanthine oxidase (XO), a key enzyme in purine metabolism, with cetyltrimethylammonium bromide (CTAB) and bis(cetyldimethylammonium)butane dibromide (C16C4C16Br2) has been studied using tensiometry, spectrofluorometry, spectrophotometry, and circular dichroism at pH 7.4 and 25 °C. The tensiometric profiles of CTAB and C16C4C16Br2 in the presence of XO exhibit a single break at a lower surfactant concentration termed as C1 compared to their CMC in the buffered solution and show the existence of interaction between the surfactants and the enzyme. The results of the multitechnique approach showed that, although both CTAB as well as C16C4C16Br2 interact with the XO, C16C4C16Br2 interacts more strongly than its conventional single chain counterpart. Fluorescence and absorption measurements revealed that, compared to CTAB, C16C4C16Br2 is more effective in unfolding the enzyme. Change in XO activity by the surfactants was in concurrence with the structural alterations monitored by circular dichroism and showed structural stabilization of XO at higher surfactant concentrations, consistent with the aggregation results. This stabilization has been explained in light of strong tendency of C16C4C16Br2 for micellar growth and membrane/water stabilization of proteins by membrane-like fragments provided by higher concentrations of C16C4C16Br2 . The results are related to the stronger electrostatic and hydrophobic forces in C16C4C16Br2, owing to the presence of two charged headgroups and two hydrophobic tails.

Electron capture in collisions of ? with H and ? with C

NASA Astrophysics Data System (ADS)

Stancil, P. C.; Gu, J.-P.; Havener, C. C.; Krstic, P. S.; Schultz, D. R.; Kimura, M.; Zygelman, B.; Hirsch, G.; Buenker, R. J.; Bannister, M. E.

1998-08-01

A comprehensive theoretical and experimental study of electron capture in collisions of 0953-4075/31/16/017/img15 with H and 0953-4075/31/16/017/img16 with C extending over the energy range 0953-4075/31/16/017/img17 to 0953-4075/31/16/017/img18 is presented. A variety of theoretical approaches were used including those based on quantal molecular-orbital close-coupling (MOCC), multielectron hidden crossings (MEHC), quantal decay and classical trajectory Monte Carlo techniques. Radiative charge transfer cross sections were computed using the optical potential/distorted wave (OPDW) and fully quantal (FQ) approaches. The MOCC, OPDW and FQ calculations incorporated ab initio potentials, nonadiabatic coupling matrix elements and transition moments computed at the configuration-interaction level. Ab initio potential surfaces in the plane of complex internuclear distance were obtained for the MEHC calculations. Merged-beam measurements were performed between 0953-4075/31/16/017/img19 and 0953-4075/31/16/017/img20 for the 0953-4075/31/16/017/img21 collision system. Diagnostics of the 0953-4075/31/16/017/img15 beam with a crossed electron beam could find no presence of a 0953-4075/31/16/017/img15 metastable component. The current results, in conjunction with previous measurements, are used to deduce a set of recommended cross sections.

N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis.

PubMed

Cui, Jian; Huang, Wan; Wu, Bo; Jin, Jin; Jing, Lin; Shi, Wen-Pu; Liu, Zhen-Yu; Yuan, Lin; Luo, Dan; Li, Ling; Chen, Zhi-Nan; Jiang, Jian-Li

2018-05-01

While the importance of protein N-glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N-acetylglucosaminyltransferase V (GnT-V) regulates cancer processes remain largely unknown. In the current study, we report that GnT-V-mediated N-glycosylation of CD147/basigin, a tumor-associated glycoprotein that carries β1,6-N-acetylglucosamine (β1,6-GlcNAc) glycans, is upregulated during TGF-β1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of β1,6-GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin β1. These results reveal that β1,6-branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT-V expression and that inhibition of GnT-V-mediated N-glycosylation suppressed PI3K signaling. In summary, β1,6-branched N-glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Neural Darwinism and consciousness.

PubMed

Seth, Anil K; Baars, Bernard J

2005-03-01

Neural Darwinism (ND) is a large scale selectionist theory of brain development and function that has been hypothesized to relate to consciousness. According to ND, consciousness is entailed by reentrant interactions among neuronal populations in the thalamocortical system (the 'dynamic core'). These interactions, which permit high-order discriminations among possible core states, confer selective advantages on organisms possessing them by linking current perceptual events to a past history of value-dependent learning. Here, we assess the consistency of ND with 16 widely recognized properties of consciousness, both physiological (for example, consciousness is associated with widespread, relatively fast, low amplitude interactions in the thalamocortical system), and phenomenal (for example, consciousness involves the existence of a private flow of events available only to the experiencing subject). While no theory accounts fully for all of these properties at present, we find that ND and its recent extensions fare well.

BOUNDS ON LEPTON FLAVOR CHANGING CURRENTS AND THE SOLAR NEUTRINO PUZZLE:. Bounds on Lepton Flavor Changing Currents

NASA Astrophysics Data System (ADS)

degl'Innocenti, Scilla; Ricci, Barbara

We present a phenomenological analysis of a lepton flavor changing current, considering the case of interactions among leptons which change the neutrino flavor and are diagonal in the charged lepton sector. In the case of νe↔νµ transition, we derive a bound on the vector coupling constant GV≤0.16 GF from experimental data on νµ-e scattering. For a transition νe↔νx, from (anti) νe-e scattering experiments and from the analysis of advanced stellar evolutionary phases, we find GV≤0.55 GF. We discuss the compatibility of these data with a possible explanation of the solar neutrino puzzle. We also analyze how the present bounds can be improved in future long baseline neutrino experiments and atmospheric neutrino detectors.

Effects of Pulse Parameters on Weld Microstructure and Mechanical Properties of Extra Pulse Current Aided Laser Welded 2219 Aluminum Alloy Joints.

PubMed

Zhang, Xinge; Li, Liqun; Chen, Yanbin; Yang, Zhaojun; Chen, Yanli; Guo, Xinjian

2017-09-15

In order to expand the application range of laser welding and improve weld quality, an extra pulse current was used to aid laser-welded 2219 aluminum alloy, and the effects of pulse current parameters on the weld microstructure and mechanical properties were investigated. The effect mechanisms of the pulse current interactions with the weld pool were evaluated. The results indicated that the coarse dendritic structure in the weld zone changed to a fine equiaxed structure using an extra pulse current, and the pulse parameters, including medium peak current, relatively high pulse frequency, and low pulse duty ratio benefited to improving the weld structure. The effect mechanisms of the pulse current were mainly ascribed to the magnetic pinch effect, thermal effect, and electromigration effect caused by the pulse current. The effect of the pulse parameters on the mechanical properties of welded joints were consistent with that of the weld microstructure. The tensile strength and elongation of the optimal pulse current-aided laser-welded joint increased by 16.4% and 105%, respectively, compared with autogenous laser welding.

Effects of Pulse Parameters on Weld Microstructure and Mechanical Properties of Extra Pulse Current Aided Laser Welded 2219 Aluminum Alloy Joints

PubMed Central

Zhang, Xinge; Li, Liqun; Chen, Yanbin; Yang, Zhaojun; Chen, Yanli; Guo, Xinjian

2017-01-01

In order to expand the application range of laser welding and improve weld quality, an extra pulse current was used to aid laser-welded 2219 aluminum alloy, and the effects of pulse current parameters on the weld microstructure and mechanical properties were investigated. The effect mechanisms of the pulse current interactions with the weld pool were evaluated. The results indicated that the coarse dendritic structure in the weld zone changed to a fine equiaxed structure using an extra pulse current, and the pulse parameters, including medium peak current, relatively high pulse frequency, and low pulse duty ratio benefited to improving the weld structure. The effect mechanisms of the pulse current were mainly ascribed to the magnetic pinch effect, thermal effect, and electromigration effect caused by the pulse current. The effect of the pulse parameters on the mechanical properties of welded joints were consistent with that of the weld microstructure. The tensile strength and elongation of the optimal pulse current-aided laser-welded joint increased by 16.4% and 105%, respectively, compared with autogenous laser welding. PMID:28914825

In vivo multimodality imaging of miRNA-16 iron nanoparticle reversing drug resistance to chemotherapy in a mouse gastric cancer model

NASA Astrophysics Data System (ADS)

Sun, Zhongchan; Song, Xinxing; Li, Xiujuan; Su, Tao; Qi, Shun; Qiao, Ruirui; Wang, Fu; Huan, Yi; Yang, Weidong; Wang, Jing; Nie, Yongzhan; Wu, Kaichun; Gao, Mingyuan; Cao, Feng

2014-11-01

miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe3O4 nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADRfluc tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr03003f

Monte Carlo studies on neutron interactions in radiobiological experiments

PubMed Central

Shahmohammadi Beni, Mehrdad; Hau, Tak Cheong; Krstic, D.; Nikezic, D.

2017-01-01

Monte Carlo method was used to study the characteristics of neutron interactions with cells underneath a water medium layer with varying thickness. The following results were obtained. (1) The fractions of neutron interaction with 1H, 12C, 14N and 16O nuclei in the cell layer were studied. The fraction with 1H increased with increasing medium thickness, while decreased for 12C, 14N and 16O nuclei. The bulges in the interaction fractions with 12C, 14N and 16O nuclei were explained by the resonance spikes in the interaction cross-section data. The interaction fraction decreased in the order: 1H > 16O > 12C > 14N. (2) In general, as the medium thickness increased, the number of “interacting neutrons” which exited the medium and then further interacted with the cell layer increased. (3) The area under the angular distributions for “interacting neutrons” decreased with increasing incident neutron energy. Such results would be useful for deciphering the reasons behind discrepancies among existing results in the literature. PMID:28704557

Cooperative Effects of Zwitterionic-Ionic Surfactant Mixtures on the Interfacial Water Structure Revealed by Sum Frequency Generation Vibrational Spectroscopy.

PubMed

Pan, Xuecong; Yang, Fangyuan; Chen, Shunli; Zhu, Xuefeng; Wang, Chuanyi

2018-05-08

Cooperative effects of a series of equimolar binary zwitterionic-ionic surfactant mixtures on the interfacial water structure at the air-water interfaces have been studied by sum frequency generation vibrational spectroscopy (SFG-VS). For zwitterionic surfactant palmityl sulfobetaine (SNC 16 ), anionic surfactant sodium hexadecyl sulfate (SHS), and cationic surfactant cetyltrimethylammonium bromide (CTAB) with the same length of alkyl chain, significantly enhanced ordering of interfacial water molecules was observed for the zwitterionic-anionic surfactant mixtures SNC 16 -SHS, indicating that SNC 16 interacts more strongly with SHS than with CTAB because of the strong headgroup-headgroup electrostatic attraction for SNC 16 -SHS. Meanwhile, the SFG amplitude ratio of methyl and methylene symmetric stretching modes was used to verify the stronger interaction between SNC 16 and SHS. The conformational order indicator increased from 0.64 for SNC 16 to 7.17 for SNC 16 -SHS but only 0.94 for SNC 16 -CTAB. In addition, another anionic surfactant sodium dodecyl sulfate (SDS) was introduced to study the influence of chain-chain interaction. Decreased SFG amplitude of interfacial water molecules for SNC 16 -SDS was observed. Therefore, both the headgroup-headgroup electrostatic interaction and chain-chain van der Waals attractive interaction of the surfactants play an important role in enhancing the ordering of interfacial water molecules. The results provided experimental and theoretical bases for practical applications of the surfactants.

A Meta-Analysis of Factors Influencing the Development of Trust in Automation: Implications for Understanding Autonomy in Future Systems.

PubMed

Schaefer, Kristin E; Chen, Jessie Y C; Szalma, James L; Hancock, P A

2016-05-01

We used meta-analysis to assess research concerning human trust in automation to understand the foundation upon which future autonomous systems can be built. Trust is increasingly important in the growing need for synergistic human-machine teaming. Thus, we expand on our previous meta-analytic foundation in the field of human-robot interaction to include all of automation interaction. We used meta-analysis to assess trust in automation. Thirty studies provided 164 pairwise effect sizes, and 16 studies provided 63 correlational effect sizes. The overall effect size of all factors on trust development was ḡ = +0.48, and the correlational effect was [Formula: see text]  = +0.34, each of which represented medium effects. Moderator effects were observed for the human-related (ḡ  = +0.49; [Formula: see text] = +0.16) and automation-related (ḡ = +0.53; [Formula: see text] = +0.41) factors. Moderator effects specific to environmental factors proved insufficient in number to calculate at this time. Findings provide a quantitative representation of factors influencing the development of trust in automation as well as identify additional areas of needed empirical research. This work has important implications to the enhancement of current and future human-automation interaction, especially in high-risk or extreme performance environments. © 2016, Human Factors and Ergonomics Society.

The association between paternal sensitivity and infant-father attachment security: a meta-analysis of three decades of research.

PubMed

Lucassen, Nicole; Tharner, Anne; Van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J; Volling, Brenda L; Verhulst, Frank C; Lambregtse-Van den Berg, Mijke P; Tiemeier, Henning

2011-12-01

For almost three decades, the association between paternal sensitivity and infant-father attachment security has been studied. The first wave of studies on the correlates of infant-father attachment showed a weak association between paternal sensitivity and infant-father attachment security (r = .13, p < .001, k = 8, N = 546). In the current paper, a meta-analysis of the association between paternal sensitivity and infant-father attachment based on all studies currently available is presented, and the change over time of the association between paternal sensitivity and infant-father attachment is investigated. Studies using an observational measure of paternal interactive behavior with the infant, and the Strange Situation Procedure to observe the attachment relationship were included. Paternal sensitivity is differentiated from paternal sensitivity combined with stimulation in the interaction with the infant. Higher levels of paternal sensitivity were associated with more infant-father attachment security (r = .12, p < .001, k = 16, N = 1,355). Fathers' sensitive play combined with stimulation was not more strongly associated with attachment security than sensitive interactions without stimulation of play. Despite possible changes in paternal role patterns, we did not find stronger associations between paternal sensitivity and infant attachment in more recent years.

Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex

PubMed Central

Hou, Jianghui; Renigunta, Aparna; Konrad, Martin; Gomes, Antonio S.; Schneeberger, Eveline E.; Paul, David L.; Waldegger, Siegfried; Goodenough, Daniel A.

2008-01-01

Tight junctions (TJs) play a key role in mediating paracellular ion reabsorption in the kidney. Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is an inherited disorder caused by mutations in the genes encoding the TJ proteins claudin-16 (CLDN16) and CLDN19; however, the mechanisms underlying the roles of these claudins in mediating paracellular ion reabsorption in the kidney are not understood. Here we showed that in pig kidney epithelial cells, CLDN19 functioned as a Cl– blocker, whereas CLDN16 functioned as a Na+ channel. Mutant forms of CLDN19 that are associated with FHHNC were unable to block Cl– permeation. Coexpression of CLDN16 and CLDN19 generated cation selectivity of the TJ in a synergistic manner, and CLDN16 and CLDN19 were observed to interact using several criteria. In addition, disruption of this interaction by introduction of FHHNC-causing mutant forms of either CLDN16 or CLDN19 abolished their synergistic effect. Our data show that CLDN16 interacts with CLDN19 and that their association confers a TJ with cation selectivity, suggesting a mechanism for the role of mutant forms of CLDN16 and CLDN19 in the development of FHHNC. PMID:18188451

PRDM16 enhances nuclear receptor-dependent transcription of the brown fat-specific Ucp1 gene through interactions with Mediator subunit MED1.

PubMed

Iida, Satoshi; Chen, Wei; Nakadai, Tomoyoshi; Ohkuma, Yoshiaki; Roeder, Robert G

2015-02-01

PR domain-containing 16 (PRDM16) induces expression of brown fat-specific genes in brown and beige adipocytes, although the underlying transcription-related mechanisms remain largely unknown. Here, in vitro studies show that PRDM16, through its zinc finger domains, directly interacts with the MED1 subunit of the Mediator complex, is recruited to the enhancer of the brown fat-specific uncoupling protein 1 (Ucp1) gene through this interaction, and enhances thyroid hormone receptor (TR)-driven transcription in a biochemically defined system in a Mediator-dependent manner, thus providing a direct link to the general transcription machinery. Complementary cell-based studies show that upon forskolin treatment, PRDM16 induces Ucp1 expression in undifferentiated murine embryonic fibroblasts, that this induction depends on MED1 and TR, and, consistent with a direct effect, that PRDM16 is recruited to the Ucp1 enhancer. Related studies have defined MED1 and PRDM16 interaction domains important for Ucp1 versus Ppargc1a induction by PRDM16. These results reveal novel mechanisms for PRDM16 function through the Mediator complex. © 2015 Iida et al.; Published by Cold Spring Harbor Laboratory Press.

Wave-current interactions at the FloWave Ocean Energy Research Facility

NASA Astrophysics Data System (ADS)

Noble, Donald; Davey, Thomas; Steynor, Jeffrey; Bruce, Tom; Smith, Helen; Kaklis, Panagiotis

2015-04-01

Physical scale model testing is an important part of the marine renewable energy development process, allowing the study of forces and device behaviour in a controlled environment prior to deployment at sea. FloWave is a new state-of-the-art ocean energy research facility, designed to provide large scale physical modelling services to the tidal and wave sector. It has the unique ability to provide complex multi-directional waves that can be combined with currents from any direction in the 25m diameter circular tank. The facility is optimised for waves around 2s period and 0.4m height, and is capable of generating currents upwards of 1.6m/s. This offers the ability to model metocean conditions suitable for most renewable energy devices at a typical scale of between 1:10 and 1:40. The test section is 2m deep, which can be classed as intermediate-depth for most waves of interest, thus the full dispersion equation must be solved as the asymptotic simplifications do not apply. The interaction between waves and currents has been studied in the tank. This has involved producing in the tank sets of regular waves, focussed wave groups, and random sea spectra including multi-directional sea states. These waves have been both inline-with and opposing the current, as well as investigating waves at arbitrary angles to the current. Changes in wave height and wavelength have been measured, and compared with theoretical results. Using theoretical wave-current interaction models, methods have been explored to "correct" the wave height in the central test area of the tank when combined with a steady current. This allows the wave height with current to be set equal to that without a current. Thus permitting, for example, direct comparison of device motion response between tests with and without current. Alternatively, this would also permit a specific wave height and current combination to be produced in the tank, reproducing recorded conditions at a particular site of interest. The initial tests used a correction factor based on a linear combination of wave and current (Smith 1997), which was found to be reasonably accurate, although the requirement for higher order theory is also explored. FloWave is a new facility that offers the ability to study wave-current interactions at arbitrary angles with relatively fast currents. This is important as waves and tidal currents at sites of interest for renewable energy generation may not be aligned (Lewis et al. 2014), and so better understanding of these conditions is required. References Lewis, M.J. et al., 2014. Realistic wave conditions and their influence on quantifying the tidal stream energy resource. Applied Energy, 136, pp.495-508. Smith, J.M., 1997. Coastal Engineering Technical Note One-dimensional wave-current interaction (CETN IV-9), Vicksburg, MS.

ZnO sublimation using a polyenergetic pulsed electron beam source: numerical simulation and validation

NASA Astrophysics Data System (ADS)

Tricot, S.; Semmar, N.; Lebbah, L.; Boulmer-Leborgne, C.

2010-02-01

This paper details the electro-thermal study of the sublimation phase on a zinc oxide surface. This thermodynamic process occurs when a ZnO target is bombarded by a pulsed electron beam source composed of polyenergetic electrons. The source delivers short pulses of 180 ns of electrons with energies up to 16 keV. The beam total current reaches 800 A and is focused onto a spot area 2 mm in diameter. The Monte Carlo CASINO program is used to study the first stage of the interaction and to define the heat source space distribution inside the ZnO target. Simulation of the second stage of interaction is developed in a COMSOL multiphysics project. The simulated thermal field induced by space and time heat conduction is presented. Typically for a pulsed electron beam 2 mm in diameter of electrons having energies up to 16 keV, the surface temperature reaches a maximum of 7000 K. The calculations are supported by SEM pictures of the target irradiated by various beam energies and numbers of pulses.

Flow visualization of CFD using graphics workstations

NASA Technical Reports Server (NTRS)

Lasinski, Thomas; Buning, Pieter; Choi, Diana; Rogers, Stuart; Bancroft, Gordon

1987-01-01

High performance graphics workstations are used to visualize the fluid flow dynamics obtained from supercomputer solutions of computational fluid dynamic programs. The visualizations can be done independently on the workstation or while the workstation is connected to the supercomputer in a distributed computing mode. In the distributed mode, the supercomputer interactively performs the computationally intensive graphics rendering tasks while the workstation performs the viewing tasks. A major advantage of the workstations is that the viewers can interactively change their viewing position while watching the dynamics of the flow fields. An overview of the computer hardware and software required to create these displays is presented. For complex scenes the workstation cannot create the displays fast enough for good motion analysis. For these cases, the animation sequences are recorded on video tape or 16 mm film a frame at a time and played back at the desired speed. The additional software and hardware required to create these video tapes or 16 mm movies are also described. Photographs illustrating current visualization techniques are discussed. Examples of the use of the workstations for flow visualization through animation are available on video tape.

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression1

PubMed Central

Woodham, Andrew W.; Raff, Adam B.; Raff, Laura M.; Da Silva, Diane M.; Yan, Lisa; Skeate, Joseph G.; Wong, Michael K.; Lin, Yvonne G.; Kast, W. Martin

2014-01-01

High-risk human papillomaviruses (HPV) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cellsin a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the antigen presenting cells of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. Here, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by siRNA downregulation of A2t, significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein. PMID:24719459

Inhibition of Langerhans cell maturation by human papillomavirus type 16: a novel role for the annexin A2 heterotetramer in immune suppression.

PubMed

Woodham, Andrew W; Raff, Adam B; Raff, Laura M; Da Silva, Diane M; Yan, Lisa; Skeate, Joseph G; Wong, Michael K; Lin, Yvonne G; Kast, W Martin

2014-05-15

High-risk human papillomaviruses (HPVs) are sexually transmitted viruses causally associated with several cancers. During its natural life cycle, HPV16, the most common high-risk genotype, infects the epithelial basal cells in a process facilitated through a recently identified receptor, the annexin A2 heterotetramer (A2t). During infection, HPV16 also interacts with Langerhans cells (LC), the APC of the epithelium, inducing immune suppression, which is mediated by the HPV16 L2 minor capsid protein. Despite the importance of these virus-immune cell interactions, the specific mechanisms of HPV16 entry into LC and HPV16-induced immune suppression remain undefined. An N-terminal peptide of HPV16 L2 (aa 108-126) has been shown to specifically interact with A2t. In this study, we show that incubation of human LC with this peptide blocks binding of HPV16. Inhibiting this interaction with an A2t ligand or by small interfering RNA downregulation of A2t significantly decreases HPV16 internalization into LC in an L2-dependent manner. A2t is associated with suppression of LC maturation as demonstrated through attenuated secretion of Th1-associated cytokines and decreased surface expression of MHC class II on LC exposed to A2t. Conversely, small molecule inhibition of A2t prevents HPV16-induced suppression of LC immune function as indicated by significantly increased secretion of inflammatory cytokines and surface expression of CD86 in HPV16 treated LC pre-exposed to A2t inhibitors. These results demonstrate that HPV16 suppresses LC maturation through an interaction with A2t, revealing a novel role for this protein.

Structural properties of the promiscuous VP16 activation domain.

PubMed

Jonker, Hendrik R A; Wechselberger, Rainer W; Boelens, Rolf; Folkers, Gert E; Kaptein, Rob

2005-01-25

Herpes simplex virion protein 16 (VP16) contains two strong activation regions that can independently and cooperatively activate transcription in vivo. We have identified the regions and residues involved in the interaction with the human transcriptional coactivator positive cofactor 4 (PC4) and the general transcription factor TFIIB. NMR and biochemical experiments revealed that both VP16 activation regions are required for the interaction and undergo a conformational transition from random coil to alpha-helix upon binding to its target PC4. The interaction is strongly electrostatically driven and the binding to PC4 is enhanced by the presence of its amino-terminal domain. We propose models for binding of VP16 to the core domains of PC4 and TFIIB that are based on two independent docking approaches using NMR chemical shift changes observed in titration experiments. The models are consistent with results from site-directed mutagenesis and provide an explanation for the contribution of both acidic and hydrophobic residues for transcriptional activation by VP16. Both intrinsically unstructured activation domains are attracted to their interaction partner by electrostatic interactions, and adopt an alpha-helical conformation around the important hydrophobic residues. The models showed multiple distinct binding surfaces upon interaction with various partners, providing an explanation for the promiscuous properties, cooperativity, and the high activity of this activation domain.

Guiding without feeling guided: Implicit scaffolding through interactive simulation design

NASA Astrophysics Data System (ADS)

Paul, Ariel; Podolefsky, Noah; Perkins, Katherine

2013-01-01

While PhET interactive simulations (sims) were historically designed for college students, they are used at lower grade levels, and we are currently developing sims targeted at middle school (MS). In studying how MS students interact with and learn from these sims, we have been extracting insights about design for the middle-grade-levels and across K-16. This collection of work has highlighted the importance of implicit scaffolding, a design framework that reduces the amount of explicit instruction needed to facilitate learning. We present a case study of redesigning a sim - Energy Skate Park (ESP) - for effective use in MS. We conducted think-aloud interviews with MS students to identify successful features, sources of confusion or unproductive distraction, as well as features inconsistent with gradeappropriate learning goals. Drawing on these data and the principle of implicit scaffolding, we developed Energy Skate Park Basics (ESPB). Interviews on ESPB demonstrate increased usability and learning for MS students.

Measurement of single π 0 production by coherent neutral-current ν Fe interactions in the MINOS Near Detector

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

Adamson, P.; Anghel, I.; Aurisano, A.

Forward single π0 production by coherent neutral-current interactions, νA→νAπ 0, is investigated using a 2.8×10 20 protons-on-target exposure of the MINOS Near Detector. For single-shower topologies, the event distribution in production angle exhibits a clear excess above the estimated background at very forward angles for visible energy in the range 1–8 GeV. Cross sections are obtained for the detector medium comprised of 80% iron and 20% carbon nuclei withmore » $$\\langle$$A$$\\rangle$$=48, the highest-$$\\langle$$A$$\\rangle$$ target used to date in the study of this coherent reaction. In conclusion, the total cross section for coherent neutral-current single π 0 production initiated by the ν μ flux of the NuMI low-energy beam with mean (mode) E ν of 4.9 GeV (3.0 GeV), is 77.6±5.0(stat)$$+15.0\\atop{-16.8}$$(syst)×10 -40 cm 2 pernucleus. Finally, the results are in good agreement with predictions of the Berger-Sehgal model.« less

Measurement of single π 0 production by coherent neutral-current ν Fe interactions in the MINOS Near Detector

DOE PAGES

Adamson, P.; Anghel, I.; Aurisano, A.; ...

2016-10-26

Forward single π0 production by coherent neutral-current interactions, νA→νAπ 0, is investigated using a 2.8×10 20 protons-on-target exposure of the MINOS Near Detector. For single-shower topologies, the event distribution in production angle exhibits a clear excess above the estimated background at very forward angles for visible energy in the range 1–8 GeV. Cross sections are obtained for the detector medium comprised of 80% iron and 20% carbon nuclei withmore » $$\\langle$$A$$\\rangle$$=48, the highest-$$\\langle$$A$$\\rangle$$ target used to date in the study of this coherent reaction. In conclusion, the total cross section for coherent neutral-current single π 0 production initiated by the ν μ flux of the NuMI low-energy beam with mean (mode) E ν of 4.9 GeV (3.0 GeV), is 77.6±5.0(stat)$$+15.0\\atop{-16.8}$$(syst)×10 -40 cm 2 pernucleus. Finally, the results are in good agreement with predictions of the Berger-Sehgal model.« less

T cell ignorance is bliss: T cells are not tolerized by Langerhans cells presenting human papillomavirus antigens in the absence of costimulation.

PubMed

Woodham, Andrew W; Yan, Lisa; Skeate, Joseph G; van der Veen, Daniel; Brand, Heike H; Wong, Michael K; Da Silva, Diane M; Kast, W Martin

2016-12-01

Human papillomavirus type 16 (HPV16) infections are intra-epithelial, and thus, HPV16 is known to interact with Langerhans cells (LCs), the resident epithelial antigen-presenting cells (APCs). The current paradigm for APC-mediated induction of T cell anergy is through delivery of T cell receptor signals via peptides on MHC molecules (signal 1), but without costimulation (signal 2). We previously demonstrated that LCs exposed to HPV16 in vitro present HPV antigens to T cells without costimulation, but it remained uncertain if such T cells would remain ignorant, become anergic, or in the case of CD4+ T cells, differentiate into Tregs. Here we demonstrate that Tregs were not induced by LCs presenting only signal 1, and through a series of in vitro immunizations show that CD8 + T cells receiving signal 1 + 2 from LCs weeks after consistently receiving signal 1 are capable of robust effector functions. Importantly, this indicates that T cells are not tolerized but instead remain ignorant to HPV, and are activated given the proper signals.

A small-molecule inhibitor of the aberrant transcription factor CBFβ-SMMHC delays leukemia in mice

PubMed Central

Illendula, Anuradha; Pulikkan, John A.; Zong, Hongliang; Grembecka, Jolanta; Xue, Liting; Sen, Siddhartha; Zhou, Yunpeng; Boulton, Adam; Kuntimaddi, Aravinda; Gao, Yan; Rajewski, Roger A.; Guzman, Monica L.; Castilla, Lucio H.; Bushweller, John H.

2015-01-01

Acute myeloid leukemia (AML) is the most common form of adult leukemia. The transcription factor fusion CBFβ-SMMHC (core binding factor β and the smooth-muscle myosin heavy chain), expressed in AML with the chromosome inversion inv(16)(p13q22), outcompetes wild-type CBFβ for binding to the transcription factor RUNX1, deregulates RUNX1 activity in hematopoiesis, and induces AML. Current inv(16) AML treatment with nonselective cytotoxic chemotherapy results in a good initial response but limited long-term survival. Here, we report the development of a protein-protein interaction inhibitor, AI-10-49, that selectively binds to CBFβ-SMMHC and disrupts its binding to RUNX1. AI-10-49 restores RUNX1 transcriptional activity, displays favorable pharmacokinetics, and delays leukemia progression in mice. Treatment of primary inv(16) AML patient blasts with AI-10-49 triggers selective cell death. These data suggest that direct inhibition of the oncogenic CBFβ-SMMHC fusion protein may be an effective therapeutic approach for inv(16) AML, and they provide support for transcription factor targeted therapy in other cancers. PMID:25678665

The Tetrodotoxin Receptor of Voltage-Gated Sodium Channels—Perspectives from Interactions with μ-Conotoxins

PubMed Central

French, Robert J.; Yoshikami, Doju; Sheets, Michael F.; Olivera, Baldomero M.

2010-01-01

Neurotoxin receptor site 1, in the outer vestibule of the conducting pore of voltage-gated sodium channels (VGSCs), was first functionally defined by its ability to bind the guanidinium-containing agents, tetrodotoxin (TTX) and saxitoxin (STX). Subsequent studies showed that peptide μ-conotoxins competed for binding at site 1. All of these natural inhibitors block single sodium channels in an all-or-none manner on binding. With the discovery of an increasing variety of μ-conotoxins, and the synthesis of numerous derivatives, observed interactions between the channel and these different ligands have become more complex. Certain μ-conotoxin derivatives block single-channel currents partially, rather than completely, thus enabling the demonstration of interactions between the bound toxin and the channel’s voltage sensor. Most recently, the relatively small μ-conotoxin KIIIA (16 amino acids) and its variants have been shown to bind simultaneously with TTX and exhibit both synergistic and antagonistic interactions with TTX. These interactions raise new pharmacological possibilities and place new constraints on the possible structures of the bound complexes of VGSCs with these toxins. PMID:20714429

Ultrafast proton radiography of the magnetic fields generated by a laser-driven coil current

DOE PAGES

Gao, Lan; Ji, Hantao; Fiksel, Gennady; ...

2016-04-15

Magnetic fields generated by a current flowing through a U-shaped coil connecting two copper foils were measured using ultrafast proton radiography. Two ~ 1.25 kJ, 1-ns laser pulses propagated through laser entrance holes in the front foil and were focused to the back foil with an intensity of ~ 3 x 10 16 W/cm 2. The intense laser-solid interaction induced a high voltage between the copper foils and generated a large current in the connecting coil. The proton data show ~ 40-50 T magnetic fields at the center of the coil ~ 3-4 ns after laser irradiation. In conclusion, themore » experiments provide significant insight for future target designs that aim to develop a powerful source of external magnetic fields for various applications in high-energy-density science.« less

Interactions between Teachers and Learning Disabled and Non-Learning Disabled Adolescents.

ERIC Educational Resources Information Center

Powell, Lynda; And Others

An observational measurement system was used to examine the interaction of 14 learning disabled (LD) students (12-15 years old) and their teachers. Interactions were compared with those of 16 non LD students (12-16 years old). It was hypothesized that LDs would have fewer interactions with their teachers and that the proportion of negative…

Observation of extreme ultraviolet transitions in highly charged Ba{sup 16+} to Ba{sup 23+} ions with electron beam ion trap

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

Ali, S.; Shimizu, E.; Nakamura, N.

2016-03-15

We have investigated extreme ultraviolet emission from highly charged barium using a compact electron beam ion trap at the Tokyo EBIT laboratory. The spectra were recorded for several beam energies ranging from 440 to 740 eV, while keeping the electron beam current constant at 10 mA. Radiation from charge states Zr-like Ba{sup 16+} to As-like Ba{sup 23+} were recorded and identified by varying the electron beam energy across the ionization thresholds and comparing with calculated results. The calculations were performed with a detailed relativistic configuration interaction approach using the Flexible Atomic Code. Several new lines belonging to electric dipole transitions were observedmore » and identified.« less

Polymorphisms of RDH16 and VEGFR1 influence M. trapezius steatosis in Japanese Black carcass.

PubMed

Ishida, Takafumi; Noda, Kosuke; Jomane, Fortune Ntengwa; Tokunaga, Tadaaki

2017-08-01

The exact cause of steatosis, one of defects in Japanese beef carcasses, has not been elucidated to date, because it is very difficult to diagnose cyclopedically with certain reproducibility due to the bias in the outbreak. Therefore, the objective of this study was to assess the influence of polymorphisms in retinol dehydrogenase 16 (RDH16), myoferlin (MYOF) and vascular endothelial growth factor receptors 1 and 2 (VEGFR1, VEGFR2) on carcass-graded Musculus trapezius steatosis. For logistic regression analysis, 646 carcasses shipped from 29 farms in Miyazaki, Japan, were used. The GG genotype in RDH16 showed significant odds ratios against AA and AG. In VEGFR1, CT had a significant odds ratio against CC. After evaluating for interaction, highly significant odds ratios were observed in the combinations that included the GG risk genotype in RDH16. It is noteworthy that there was no steatosis in the combination GG (RDH16) and CC (VEGFR1). It may be concluded that there is a possibility that steatosis can be suppressed by the CC genotype in VEGFR1. The current study revealed the influence of genetic polymorphisms on M. trapezius steatosis that had not been reported until now, and may help elucidate the cause of steatosis. © 2016 Japanese Society of Animal Science.

Similarity-transformed chiral NN + 3N interactions for the ab initio description of 12C and 16O.

PubMed

Roth, Robert; Langhammer, Joachim; Calci, Angelo; Binder, Sven; Navrátil, Petr

2011-08-12

We present first ab initio no-core shell model (NCSM) calculations using similarity renormalization group (SRG) transformed chiral two-nucleon (NN) plus three-nucleon (3N) interactions for nuclei throughout the p-shell, particularly (12)C and (16)O. By introducing an adaptive importance truncation for the NCSM model space and an efficient JT-coupling scheme for the 3N matrix elements, we are able to surpass previous NCSM studies including 3N interactions. We present ground and excited states in (12)C and (16)O for model spaces up to N(max) = 12 including full 3N interactions. We analyze the contributions of induced and initial 3N interactions and probe induced 4N terms through the sensitivity of the energies on the SRG flow parameter. Unlike for light p-shell nuclei, SRG-induced 4N contributions originating from the long-range two-pion terms of the chiral 3N interaction are sizable in (12)C and (16)O.

Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression

PubMed Central

Traurig, Michael; Hanson, Robert L.; Marinelarena, Alejandra; Kobes, Sayuko; Piaggi, Paolo; Cole, Shelley; Curran, Joanne E.; Blangero, John; Göring, Harald; Kumar, Satish; Nelson, Robert G.; Howard, Barbara V.; Knowler, William C.; Baier, Leslie J.

2016-01-01

Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10−7) such that the diabetes association was stronger in leaner individuals. rs75493593 was also strongly associated with BMI in individuals with type 2 diabetes (P = 3.4 × 10−15) but not in individuals without diabetes (P = 0.77). Longitudinal analyses suggest that this is due, in part, to an association of the A allele with greater weight loss following diabetes onset (P = 0.02). Analyses of global gene expression data from adipose tissue, skeletal muscle, and whole blood provide evidence that rs75493593 is associated with expression of the nearby RNASEK gene, suggesting that RNASEK expression may mediate the effect of genotype on diabetes. PMID:26487785

Prognostic impact of HPV-associated p16-expression and smoking status on outcomes following radiotherapy for oropharyngeal cancer: The MARCH-HPV project.

PubMed

Lassen, Pernille; Lacas, Benjamin; Pignon, Jean-Pierre; Trotti, Andy; Zackrisson, Bjorn; Zhang, Qiang; Overgaard, Jens; Blanchard, Pierre

2018-01-01

Evaluate the prognostic and predictive impact of HPV-associated p16-expression and assess the combined prognostic impact of p16 and smoking on altered fractionated radiotherapy (AFRT) for oropharyngeal cancer (OPC) within the frames of the update of the Meta-Analysis of Radiotherapy in Carcinomas of Head and neck (MARCH). Patients with OPC, known tumor p16-status and smoking history were identified from the MARCH update, resulting in a dataset of 815 patients from four randomized trials (RTOG9003, DAHANCA6&7, RTOG0129, ARTSCAN). Analysis was performed using a Cox model stratified by trial and adjusted on gender, age, T-stage, N-stage, type of radiotherapy fractionation, p16, smoking. Primary endpoint was progression-free survival (PFS). In total, 465 patients (57%) had p16-positive tumors and 350 (43%) p16-negative. Compared to p16-negative, p16-positive patients had significantly better PFS (HR = 0.42 [95% CI: 0.34-0.51], 28.9% absolute increase at 10 years) and OS (HR = 0.40 [0.32-0.49], 32.1% absolute increase at 10 years). No interaction between p16-status and fractionation schedule was detected. Smoking negatively impacted outcome; in the p16-positive subgroup, never smokers had significantly better PFS than former/current smokers (HR = 0.49 [0.33-0.75], 24.2% survival benefit at 10 years). No predictive impact of p16-status on response to AFRT could be detected but the strong prognostic impact of p16-status was confirmed and especially p16-positive never smoking patients have superior outcome after RT. Copyright © 2017 Elsevier B.V. All rights reserved.

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

PubMed Central

Starkey, Jason L.; Han, Jun; Chadha, Pooja; Marsh, Jacob A.

2014-01-01

UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among all members of the Herpesviridae, but its function is poorly understood. Previous studies revealed that UL16 is associated with capsids in the cytoplasm and interacts with the membrane protein UL11, which suggested a “bridging” function during cytoplasmic envelopment, but this conjecture has not been tested. To gain further insight, cells infected with UL16-null mutants were examined by electron microscopy. No defects in the transport of capsids to cytoplasmic membranes were observed, but the wrapping of capsids with membranes was delayed. Moreover, clusters of cytoplasmic capsids were often observed, but only near membranes, where they were wrapped to produce multiple capsids within a single envelope. Normal virion production was restored when UL16 was expressed either by complementing cells or from a novel position in the HSV genome. When the composition of the UL16-null viruses was analyzed, a reduction in the packaging of glycoprotein E (gE) was observed, which was not surprising, since it has been reported that UL16 interacts with this glycoprotein. However, levels of the tegument protein VP22 were also dramatically reduced in virions, even though this gE-binding protein has been shown not to depend on its membrane partner for packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in the absence of other viral proteins. These results extend the UL16 interaction network beyond its previously identified binding partners to include VP22 and provide evidence that UL16 plays an important function at the membrane during virion production. PMID:24131716

Short peptides derived from the interaction domain of SARS coronavirus nonstructural protein nsp10 can suppress the 2'-O-methyltransferase activity of nsp10/nsp16 complex.

PubMed

Ke, Min; Chen, Yu; Wu, Andong; Sun, Ying; Su, Ceyang; Wu, Hao; Jin, Xu; Tao, Jiali; Wang, Yi; Ma, Xiao; Pan, Ji-An; Guo, Deyin

2012-08-01

Coronaviruses are the etiological agents of respiratory and enteric diseases in humans and livestock, exemplified by the life-threatening severe acute respiratory syndrome (SARS) caused by SARS coronavirus (SARS-CoV). However, effective means for combating coronaviruses are still lacking. The interaction between nonstructural protein (nsp) 10 and nsp16 has been demonstrated and the crystal structure of SARS-CoV nsp16/10 complex has been revealed. As nsp10 acts as an essential trigger to activate the 2'-O-methyltransferase activity of nsp16, short peptides derived from nsp10 may have inhibitory effect on viral 2'-O-methyltransferase activity. In this study, we revealed that the domain of aa 65-107 of nsp10 was sufficient for its interaction with nsp16 and the region of aa 42-120 in nsp10, which is larger than the interaction domain, was needed for stimulating the nsp16 2'-O-methyltransferase activity. We further showed that two short peptides derived from the interaction domain of nsp10 could inhibit the 2'-O-methyltransferase activity of SARS-CoV nsp16/10 complex, thus providing a novel strategy and proof-of-principle study for developing peptide inhibitors against SARS-CoV. Copyright © 2012 Elsevier B.V. All rights reserved.

Studies into the anxiolytic actions of agomelatine in social isolation reared rats: Role of corticosterone and sex.

PubMed

Regenass, Wilmie; Möller, Marisa; Harvey, Brian H

2018-02-01

Anxiety disorders are severely disabling, while current pharmacological treatments are complicated by delayed onset, low remission rates and side-effects. Sex is also noted to contribute towards illness severity and treatment response. Agomelatine is a melatonin (MT 1 /MT 2 ) agonist and serotonin (5-HT 2C ) antagonist purported to be anxiolytic in clinical and some pre-clinical studies. We undertook a detailed analysis of agomelatine's anxiolytic activity in a neurodevelopmental model of anxiety, the social isolation reared rat. Rats received sub-chronic treatment with vehicle or agomelatine (40 mg/kg per day intraperitoneally at 16:00 h for 16 days), with behaviour analysed in the open field test, social interaction test and elevated plus maze. The contribution of corticosterone and sex was also studied. Social isolation rearing increased locomotor activity and reduced social interaction in the social interaction test, and was anxiogenic in the elevated plus maze in males and females. Agomelatine reversed these behaviours. Male and female social isolation reared rats developed anxiety-like behaviours to a similar degree, although response to agomelatine was superior in male rats. Social isolation rearing decreased plasma corticosterone in both sexes and tended to higher levels in females, although agomelatine did not affect corticosterone in either sex. Concluding, agomelatine is anxiolytic in SIR rats, although correcting altered corticosterone could not be implicated. Sex-related differences in the response to agomelatine are evident.

House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population.

PubMed

Carnes, Megan Ulmer; Hoppin, Jane A; Metwali, Nervana; Wyss, Annah B; Hankinson, John L; O'Connell, Elizabeth Long; Richards, Marie; Long, Stuart; Freeman, Laura E Beane; Sandler, Dale P; Henneberger, Paul K; Barker-Cummings, Christie; Umbach, David M; Thorne, Peter S; London, Stephanie J

2017-03-01

Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations. To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population. Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case-control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression. Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14-1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02-1.37; not born on a farm: OR, 1.67; 95% CI, 1.26-2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV 1 /FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791. House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma.

Plasmasphere-Ring Current-Radiation Belts Interactions: Review of 16 Years of Cluster Observations

NASA Astrophysics Data System (ADS)

Dandouras, I. S.

2016-12-01

The Cluster mission is based on four identical spacecraft launched in 2000 on similar elliptical polar orbits with an initial perigee at about 4 RE and an apogee at 19.6 RE. This allows Cluster to cross the outer plasmasphere, the ring current region and the radiation belts, from south to north, during every perigee pass and to obtain their latitudinal profile following almost the same flux tube. Due to various perturbations the perigee geocentric distance decreased during 2007-2010 to about 2 RE, whereas actually it is again up to about 5 RE, allowing in this way to study, during the mission, the inner magnetosphere populations and their interactions at a wide range of L-shells and under different solar activity conditions. The CIS experiment, on board these spacecraft, provides the ion distribution functions from 1 eV (plasmasphere populations) up to 40 keV (ring current), whereas the MeV penetrating particles allow to monitor the position and dynamics of the radiation belts. The FGM experiment on board these four spacecraft allowed for the first time an instantaneous calculation of the magnetic field gradients and thus a direct measurement of the local current density using the curlometer technique. Earlier and more recent results, based on Cluster data acquired during the passes in inner magnetosphere, will be reviewed and analysed.

Macrolides versus azalides: a drug interaction update.

PubMed

Amsden, G W

1995-09-01

To describe the current drug interaction profiles for all approved and investigational macrolide and azalide antimicrobials, and to comment on the clinical impact of these interactions when appropriate. MEDLINE was searched to identify all pertinent studies, review articles, and case reports from 1975 to 1995. When appropriate information was not available in the literature, data were obtained from the product manufacturers. All available data were reviewed to give an unbiased account of possible drug interactions. Data for some of the interactions were not available from the literature, but were available from abstracts or from company-supplied materials. Although the data were not always entirely explicative, the best attempt was made to deliver the pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied in the form of a review or study report, a thorough explanation of pertinent methodology was supplied. Since the introduction of erythromycin into clinical practice, there have been several clinically significant drug interactions identified throughout the literature associated with this drug. These interactions have been caused mostly by inhibition of the CYP3A subclass of hepatic enzymes, thereby decreasing the metabolism of any other agent given concurrently that is also cleared through this mechanism. With the development and marketing of several new macrolides, it was hoped that the drug interaction profile associated with this class would improve. This has been met with variable success. Although some of the extensions of the 14-membered ring macrolides have shown an incidence of interactions equal to that of erythromycin, others have shown improved profiles. In contrast, the 16-membered ring macrolides have demonstrated a much improved, though not absent, interaction profile. The most success in avoiding drug interactions through structure modification has been accomplished with the development of the azalide class, of which azithromycin is the first to be approved for marketing. This agent has to date produced none of the classic drug interactions that most macrolides have demonstrated in patient care. The introduction of new 14- and 16-membered ring macrolides appears to have had a variable effect in modifying the incidence of drug interactions associated with this class. Azithromycin, a member of the new azalide class, has to date produced fewer clinically significant interactions than other azalides with any agent that is cleared through the CYP3A system.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrafast proton radiography of the magnetic fields generated by a laser-driven coil current

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

Gao, Lan; Ji, Hantao; Princeton Plasma Physics Laboratory, Princeton University, Princeton, New Jersey 08543

2016-04-15

Magnetic fields generated by a current flowing through a U-shaped coil connecting two copper foils were measured using ultrafast proton radiography. Two ∼1.25 kJ, 1-ns laser pulses propagated through laser entrance holes in the front foil and were focused to the back foil with an intensity of ∼3 × 10{sup 16 }W/cm{sup 2}. The intense laser-solid interaction induced a high voltage between the copper foils and generated a large current in the connecting coil. The proton data show ∼40–50 T magnetic fields at the center of the coil ∼3–4 ns after laser irradiation. The experiments provide significant insight for future target designs that aim tomore » develop a powerful source of external magnetic fields for various applications in high-energy-density science.« less

Microstructural characterization of annealed U-12Zr-4Pd and U-12Zr-4Pd-5Ln: Investigating Pd as a metallic fuel additive

NASA Astrophysics Data System (ADS)

Benson, Michael T.; He, Lingfeng; King, James A.; Mariani, Robert D.

2018-04-01

Palladium is being investigated as a potential additive to metallic fuel to control fuel-cladding chemical interaction (FCCI). A primary cause of FCCI is the lanthanide fission products moving to the fuel periphery and interacting with the cladding. This interaction will lead to wastage of the cladding and, given enough time or burn-up, eventually to a cladding breach. The current study is a scanning electron microscopy (SEM) and transmission electron microscopy (TEM) characterization of annealed U-12Zr-4Pd and U-12Zr-4Pd-5Ln, where Ln = 53Nd-25Ce-16Pr-6La. The present study shows that Pd preferentially binds the lanthanides over other fuel constituents, which may prevent lanthanide migration and interaction with the cladding during irradiation. The SEM analysis indicates the 1:1 Pd-Ln compound is being formed, while the TEM analysis, due to higher resolution, found the 1:1 compound, as well as Pd-rich compounds Pd2Ln and Pd3Ln2.

Study of charged—current ep interactions at Q 2>200 GeV2 with the ZEUS detector at HERA

NASA Astrophysics Data System (ADS)

Derrick, M.; Krakauer, D.; Magill, S.; Mikunas, D.; Musgrave, B.; Okrasinski, J. R.; Repond, J.; Stanek, R.; Talaga, R. L.; Zhang, H.; Mattingly, M. C. K.; Antonioli, P.; Bari, G.; Basile, M.; Bellagamba, L.; Boscherini, D.; Bruni, A.; Bruni, G.; Bruni, P.; Romeo, G. Cara; Castellini, G.; Cifarelli, L.; Cindolo, F.; Contin, A.; Corradi, M.; Gialas, I.; Giusti, P.; Iacobucci, G.; Laurenti, G.; Levi, G.; Margotti, A.; Massam, T.; Nania, R.; Palmonari, F.; Pesci, A.; Polini, A.; Sartorelli, G.; Garcia, Y. Zamora; Zichichi, A.; Amelung, C.; Bornheim, A.; Crittenden, J.; Deffner, R.; Doeker, T.; Eckert, M.; Feld, L.; Frey, A.; Geerts, M.; Grothe, M.; Hartmann, H.; Heinloth, K.; Heinz, L.; Hilger, E.; Jakob, H.-P.; Katz, U. F.; Mengel, S.; Paul, E.; Pfeiffer, M.; Rembser, Ch.; Schramm, D.; Stamm, J.; Wedemeyer, R.; Campbell-Robson, S.; Cassidy, A.; Cottingham, W. N.; Dyce, N.; Foster, B.; George, S.; Hayes, M. E.; Heath, G. P.; Heath, H. F.; Piccioni, D.; Roff, D. G.; Tapper, R. J.; Yoshida, R.; Arneodo, M.; Ayad, R.; Capua, M.; Garfagnini, A.; Iannotti, L.; Schioppa, M.; Susinno, G.; Caldwell, A.; Cartiglia, N.; Jing, Z.; Liu, W.; Parsons, J. A.; Ritz, S.; Sciulli, F.; Straub, P. B.; Wai, L.; Yang, S.; Zhu, Q.; Borzemski, P.; Chwastowski, J.; Eskreys, A.; Jakubowski, Z.; Przybycień, M. B.; Zachara, M.; Zawiejski, L.; Adamczyk, L.; Bednarek, B.; Jeleń, K.; Kisielewska, D.; Kowalski, T.; Przybycień, M.; Rulikowska-Zarębska, E.; Suszycki, L.; Zając, J.; Duliński, Z.; Kotański, A.; Abbiendi, G.; Bauerdick, L. A. T.; Behrens, U.; Beier, H.; Bienlein, J. K.; Cases, G.; Deppe, O.; Desler, K.; Drews, G.; Flasiński, M.; Gilkinson, D. J.; Glasman, C.; Göttlicher, P.; Große-Knetter, J.; Haas, T.; Hain, W.; Hasell, D.; Heßling, H.; Iga, Y.; Johnson, K. F.; Joos, P.; Kasemann, M.; Klanner, R.; Koch, W.; Kötz, U.; Kowalski, H.; Labs, J.; Ladage, A.; Löhr, B.; Löwe, M.; Lüke, D.; Mainusch, J.; Mańczak, O.; Milewski, J.; Monteiro, T.; Ng, J. S. T.; Notz, D.; Ohrenberg, K.; Piotrzkowski, K.; Roco, M.; Rohde, M.; Roldán, J.; Schneekloth, U.; Schulz, W.; Selonke, F.; Surrow, B.; Tassi, E.; Voß, T.; Westphal, D.; Wolf, G.; Wollmer, U.; Youngman, C.; Zeuner, W.; Grabosch, H. J.; Kharchilava, A.; Mari, S. M.; Meyer, A.; Schlenstedt, S.; Wulff, N.; Barbagli, G.; Gallo, E.; Pelfer, P.; Maccarrone, G.; de Pasquale, S.; Votano, L.; Bamberger, A.; Eisenhardt, S.; Trefzger, T.; Wölfle, S.; Bromley, J. T.; Brook, N. H.; Bussey, P. J.; Doyle, A. T.; Saxon, D. H.; Sinclair, L. E.; Utley, M. L.; Wilson, A. S.; Dannemann, A.; Holm, U.; Horstmann, D.; Sinkus, R.; Wick, K.; Burow, B. D.; Hagge, L.; Lohrmann, E.; Poelz, G.; Schott, W.; Zetsche, F.; Bacon, T. C.; Brümmer, N.; Butterworth, I.; Harris, V. L.; Howell, G.; Hung, B. H. Y.; Lamberti, L.; Long, K. R.; Miller, D. B.; Pavel, N.; Prinias, A.; Sedgbeer, J. K.; Sideris, D.; Whitfield, A. F.; Mallik, U.; Wang, M. Z.; Wang, S. M.; Wu, J. T.; Cloth, P.; Filges, D.; An, S. H.; Cho, G. H.; Ko, B. J.; Lee, S. B.; Nam, S. W.; Park, H. S.; Park, S. K.; Kartik, S.; Kim, H.-J.; McNeil, R. R.; Metcalf, W.; Nadendla, V. K.; Barreiro, F.; Fernandez, J. P.; Graciani, R.; Hernández, J. M.; Hervás, L.; Labarga, L.; Martinez, M.; Del Peso, J.; Puga, J.; Terron, J.; de Trocóniz, J. F.; Corriveau, F.; Hanna, D. S.; Hartmann, J.; Hung, L. W.; Lim, J. N.; Matthews, C. G.; Patel, P. M.; Riveline, M.; Stairs, D. G.; St-Laurent, M.; Ullmann, R.; Zacek, G.; Tsurugai, T.; Bashkirov, V.; Dolgoshein, B. A.; Stifutkin, A.; Bashindzhagyan, G. L.; Ermolov, P. F.; Gladilin, L. K.; Golubkov, Yu. A.; Kobrin, V. D.; Korzhavina, I. A.; Kuzmin, V. A.; Lukina, O. Yu.; Proskuryakov, A. S.; Savin, A. A.; Shcheglova, L. M.; Solomin, A. N.; Zotov, N. P.; Botje, M.; Chlebana, F.; Engelen, J.; de Kamps, M.; Kooijman, P.; Kruse, A.; van Sighem, A.; Tiecke, H.; Verkerke, W.; Vossebeld, J.; Vreeswijk, M.; Wiggers, L.; de Wolf, E.; van Woudenberg, R.; Acosta, D.; Bylsma, B.; Durkin, L. S.; Gilmore, J.; Li, C.; Ling, T. Y.; Nylander, P.; Park, I. H.; Romanowski, T. A.; Bailey, D. S.; Cashmore, R. J.; Cooper-Sarkar, A. M.; Devenish, R. C. E.; Harnew, N.; Lancaster, M.; Lindemann, L.; McFall, J. D.; Nath, C.; Noyes, V. A.; Quadt, A.; Tickner, J. R.; Uijterwaal, H.; Walczak, R.; Waters, D. S.; Wilson, F. F.; Yip, T.; Bertolin, A.; Brugnera, R.; Carlin, R.; Dal Corso, F.; de Giorgi, M.; Dosselli, U.; Limentani, S.; Morandin, M.; Posocco, M.; Stanco, L.; Stroili, R.; Voci, C.; Zuin, F.; Bulmahn, J.; Feild, R. G.; Oh, B. Y.; Whitmore, J. J.; D'Agostini, G.; Marini, G.; Nigro, A.; Hart, J. C.; McCubbin, N. A.; Shah, T. P.; Barberis, E.; Dubbs, T.; Heusch, C.; van Hook, M.; Lockman, W.; Rahn, J. T.; Sadrozinski, H. F.-W.; Seiden, A.; Williams, D. C.; Biltzinger, J.; Seifert, R. J.; Schwarzer, O.; Walenta, A. H.; Abramowicz, H.; Briskin, G.; Dagan, S.; Levy, A.; Fleck, J. I.; Inuzuka, M.; Ishii, T.; Kuze, M.; Mine, S.; Nakao, M.; Suzuki, I.; Tokushuku, K.; Umemori, K.; Yamada, S.; Yamazaki, Y.; Chiba, M.; Hamatsu, R.; Hirose, T.; Homma, K.; Kitamura, S.; Matsushita, T.; Yamauchi, K.; Cirio, R.; Costa, M.; Ferrero, M. I.; Maselli, S.; Peroni, C.; Sacchi, R.; Solano, A.; Staiano, A.; Dardo, M.; Bailey, D. C.; Benard, F.; Brkic, M.; Fagerstroem, C.-P.; Hartner, G. F.; Joo, K. K.; Levman, G. M.; Martin, J. F.; Orr, R. S.; Polenz, S.; Sampson, C. R.; Simmons, D.; Teuscher, R. J.; Butterworth, J. M.; Catterall, C. D.; Jones, T. W.; Kaziewicz, P. B.; Lane, J. B.; Saunders, R. L.; Shulman, J.; Sutton, M. R.; Lu, B.; Mo, L. W.; Bogusz, W.; Ciborowski, J.; Gajewski, J.; Grzelak, G.; Kasprzak, M.; Krzyżanowski, M.; Muchorowski, K.; Nowak, R. J.; Pawlak, J. M.; Tymieniecka, T.; Wróblewski, A. K.; Zakrzewski, J. A.; Żarnecki, A. F.; Adamus, M.; Coldewey, C.; Eisenberg, Y.; Hochman, D.; Karshon, U.; Revel, D.; Zer-Zion, D.; Badgett, W. F.; Breitweg, J.; Chapin, D.; Cross, R.; Dasu, S.; Foudas, C.; Loveless, R. J.; Mattingly, S.; Reeder, D. D.; Silverstein, S.; Smith, W. H.; Vaiciulis, A.; Wodarczyk, M.; Bhadra, S.; Cardy, M. L.; Frisken, W. R.; Khakzad, M.; Murray, W. N.; Schmidke, W. B.

1996-12-01

Deep inelastic charged-current reactions have been studied in e + p and e - p collisions at a center of mass energy of about 300GeV in the kinematic region Q 2>200GeV2 and x>0.006 using the ZEUS detector at HERA. The integrated cross sections for Q 2>200GeV2 are found to be σ _{e^ + p to bar ν X} = 30.3_{ - 4.2 - 2.6}^{ + 5.5 + 1.6} pb and σ _{e^ - p to ν X} = 54.7_{ - 9.8 - 3.4}^{ + 15.9 + 2.8} pb . Differential cross sections have been measured as functions of the variables x, y and Q 2. From the measured differential cross sections dσ/dQ 2, the W boson mass is determined to be M_W = 79_{ - 7 - 4}^{ + 8 + 4} GeV . Measured jet rates and transverse energy profiles agree with model predictions. A search for charged-current interactions with a large rapidity gap yielded one candidate event, corresponding to a cross section of σ _{e^ + p to bar ν X} (Q^2 > 200 GeV^2 ; η _{max }< 2.5) = 0.8_{ - 0.7}^{ + 1.8} ± 0.1 pb

Transcranial direct current stimulation (tDCS) facilitates overall visual search response times but does not interact with visual search task factors

PubMed Central

Gordon, Barry

2018-01-01

Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages. PMID:29558513

Transcranial direct current stimulation (tDCS) facilitates overall visual search response times but does not interact with visual search task factors.

PubMed

Sung, Kyongje; Gordon, Barry

2018-01-01

Whether transcranial direct current stimulation (tDCS) affects mental functions, and how any such effects arise from its neural effects, continue to be debated. We investigated whether tDCS applied over the visual cortex (Oz) with a vertex (Cz) reference might affect response times (RTs) in a visual search task. We also examined whether any significant tDCS effects would interact with task factors (target presence, discrimination difficulty, and stimulus brightness) that are known to selectively influence one or the other of the two information processing stages posited by current models of visual search. Based on additive factor logic, we expected that the pattern of interactions involving a significant tDCS effect could help us colocalize the tDCS effect to one (or both) of the processing stages. In Experiment 1 (n = 12), anodal tDCS improved RTs significantly; cathodal tDCS produced a nonsignificant trend toward improvement. However, there were no interactions between the anodal tDCS effect and target presence or discrimination difficulty. In Experiment 2 (n = 18), we manipulated stimulus brightness along with target presence and discrimination difficulty. Anodal and cathodal tDCS both produced significant improvements in RTs. Again, the tDCS effects did not interact with any of the task factors. In Experiment 3 (n = 16), electrodes were placed at Cz and on the upper arm, to test for a possible effect of incidental stimulation of the motor regions under Cz. No effect of tDCS on RTs was found. These findings strengthen the case for tDCS having real effects on cerebral information processing. However, these effects did not clearly arise from either of the two processing stages of the visual search process. We suggest that this is because tDCS has a DIFFUSE, pervasive action across the task-relevant neuroanatomical region(s), not a discrete effect in terms of information processing stages.

A 16-Gene Signature Distinguishes Anaplastic Astrocytoma from Glioblastoma

PubMed Central

Rao, Soumya Alige Mahabala; Srinivasan, Sujaya; Patric, Irene Rosita Pia; Hegde, Alangar Sathyaranjandas; Chandramouli, Bangalore Ashwathnarayanara; Arimappamagan, Arivazhagan; Santosh, Vani; Kondaiah, Paturu; Rao, Manchanahalli R. Sathyanarayana; Somasundaram, Kumaravel

2014-01-01

Anaplastic astrocytoma (AA; Grade III) and glioblastoma (GBM; Grade IV) are diffusely infiltrating tumors and are called malignant astrocytomas. The treatment regimen and prognosis are distinctly different between anaplastic astrocytoma and glioblastoma patients. Although histopathology based current grading system is well accepted and largely reproducible, intratumoral histologic variations often lead to difficulties in classification of malignant astrocytoma samples. In order to obtain a more robust molecular classifier, we analysed RT-qPCR expression data of 175 differentially regulated genes across astrocytoma using Prediction Analysis of Microarrays (PAM) and found the most discriminatory 16-gene expression signature for the classification of anaplastic astrocytoma and glioblastoma. The 16-gene signature obtained in the training set was validated in the test set with diagnostic accuracy of 89%. Additionally, validation of the 16-gene signature in multiple independent cohorts revealed that the signature predicted anaplastic astrocytoma and glioblastoma samples with accuracy rates of 99%, 88%, and 92% in TCGA, GSE1993 and GSE4422 datasets, respectively. The protein-protein interaction network and pathway analysis suggested that the 16-genes of the signature identified epithelial-mesenchymal transition (EMT) pathway as the most differentially regulated pathway in glioblastoma compared to anaplastic astrocytoma. In addition to identifying 16 gene classification signature, we also demonstrated that genes involved in epithelial-mesenchymal transition may play an important role in distinguishing glioblastoma from anaplastic astrocytoma. PMID:24475040

Secreted CLCA1 modulates TMEM16A to activate Ca(2+)-dependent chloride currents in human cells.

PubMed

Sala-Rabanal, Monica; Yurtsever, Zeynep; Nichols, Colin G; Brett, Tom J

2015-03-17

Calcium-activated chloride channel regulator 1 (CLCA1) activates calcium-dependent chloride currents; neither the target, nor mechanism, is known. We demonstrate that secreted CLCA1 activates calcium-dependent chloride currents in HEK293T cells in a paracrine fashion, and endogenous TMEM16A/Anoctamin1 conducts the currents. Exposure to exogenous CLCA1 increases cell surface levels of TMEM16A and cellular binding experiments indicate CLCA1 engages TMEM16A on the surface of these cells. Altogether, our data suggest that CLCA1 stabilizes TMEM16A on the cell surface, thus increasing surface expression, which results in increased calcium-dependent chloride currents. Our results identify the first Cl(-) channel target of the CLCA family of proteins and establish CLCA1 as the first secreted direct modifier of TMEM16A activity, delineating a unique mechanism to increase currents. These results suggest cooperative roles for CLCA and TMEM16 proteins in influencing the physiology of multiple tissues, and the pathology of multiple diseases, including asthma, COPD, cystic fibrosis, and certain cancers.

Proteomic analysis of the herpes simplex virus 1 virion protein 16 transactivator protein in infected cells.

PubMed

Suk, Hyung; Knipe, David M

2015-06-01

The herpes simplex virus 1 virion protein 16 (VP16) tegument protein forms a transactivation complex with the cellular proteins host cell factor 1 (HCF-1) and octamer-binding transcription factor 1 (Oct-1) upon entry into the host cell. VP16 has also been shown to interact with a number of virion tegument proteins and viral glycoprotein H to promote viral assembly, but no comprehensive study of the VP16 proteome has been performed at early times postinfection. We therefore performed a proteomic analysis of VP16-interacting proteins at 3 h postinfection. We confirmed the interaction of VP16 with HCF-1 and a large number of cellular Mediator complex proteins, but most surprisingly, we found that the major viral protein associating with VP16 is the infected cell protein 4 (ICP4) immediate-early (IE) transactivator protein. These results raise the potential for a new function for VP16 in associating with the IE ICP4 and playing a role in transactivation of early and late gene expression, in addition to its well-documented function in transactivation of IE gene expression. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

USAFSAM Review and Analysis of Radiofrequency Radiation Bioeffects Literature: Second Report.

DTIC Science & Technology

1982-05-01

10 Cellular 11 Mechanisms of interaction 12 Environmental 13 Medical applications 14 Review 15 Ecological 16 Physical methods/dosimetry 17 Other 18...APPLICATIONS List of Analyses ......... .................... 137 (14) REVIEW List of Analyses ......... .................... 138 (16) PHYSICAL METHODS/DOSIMETRY...physiological 10 Cellular 11 Mechanisms of interaction 12 Environmental 13 Medical applications 14 Review 15 Ecological 16 Physical methods/dosimetry 17

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta - analysis.

PubMed

Vaessen, Thomas Stephanus Johannes; de Jong, Lea; Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Smeets, Antonius Petrus Wilhelmus; Ermiş, Ayşegül; Kennedy, James L; Nieman, Dorien H; Tiwari, Arun; van Os, Jim; Drukker, Marjan

2018-01-01

Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). PubMed, Embase, PsychInfo. All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05-2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16-0.08). A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing.

p16 Protein and Gigaxonin Are Associated with the Ubiquitination of NFκB in Cisplatin-induced Senescence of Cancer Cells*

PubMed Central

Veena, Mysore S.; Wilken, Reason; Zheng, Jun-Ying; Gholkar, Ankur; Venkatesan, Natarajan; Vira, Darshni; Ahmed, Sameer; Basak, Saroj K.; Dalgard, Clifton L.; Ravichandran, Sandhiya; Batra, Raj K.; Kasahara, Noriyuki; Elashoff, David; Fishbein, Michael C.; Whitelegge, Julian P.; Torres, Jorge Z.; Wang, Marilene B.; Srivatsan, Eri S.

2014-01-01

The molecular mechanism of p16-mediated senescence in cisplatin-treated cancer cells is not fully understood. Here we show that cisplatin treatment of head and neck cancer cells results in nuclear transport of p16 leading to a molecular modification of NFκB. Chromatin immunoprecipitation assays show that this modification is associated with the inhibition of NFκB interacting with its DNA binding sequences, leading to decreased expression of NFκB-transcribed proteins. LCMS proteomic analysis of LAP-TAP-purified proteins from HeLa cells containing a tetracycline-inducible GFP-S peptide-NFκB expression system identified gigaxonin, an ubiquitin E3 ligase adaptor, as an NFκB-interacting protein. Immunoblotting and siRNA studies confirmed the NFκB-gigaxonin interaction and the dependence of this binding on p16-NFκB binding. Using gel shift assays, we have confirmed p16-NFκB and gigaxonin-NFκB interactions. Furthermore, we have observed increased NFκB ubiquitination with cisplatin treatment that is abolished in the absence of p16 and gigaxonin expression. Analysis of 103 primary tumors has shown that increased nuclear p16 expression correlates with enhanced survival of head and neck cancer patients (p < 0.0000542), indicating the importance of nuclear p16 expression in prognosis. Finally, p16 expression is associated with reduced cytokine expression and the presence of human papilloma virus in chemoradiation-sensitive basaloid tumors. However, the absence of p16 expression is associated with enhanced cytokine expression and the absence of human papilloma virus in aggressive tumors. These results clearly demonstrate that nuclear p16 and gigaxonin play an important role in chemosensitivity of head and neck cancers through ubiquitination of NFκB. PMID:25331947

Hyperfine interaction constants of 14NO2 in 14 500-16 800 cm-1 energy region

NASA Astrophysics Data System (ADS)

Tada, Kohei; Hirata, Michihiro; Kasahara, Shunji

2017-10-01

We observed hyperfine-resolved high-resolution fluorescence excitation spectra of k = 0, N = 1 ← 0 transitions in 82 vibronic bands of the à 2B2 ← X ˜ 2A1 system of 14NO2 in the 14 500-16 800 cm-1 region by crossing a jet-cooled molecular beam and a single-mode dye laser beam at right angles. We determined hyperfine interaction constants of the lower and upper states for all the observed vibronic bands based on the analysis of the hyperfine structures of k = 0, N = 1 ← 0 transitions. Most of the determined Fermi contact interaction constants were found to be distributed in 0.0013-0.0038 cm-1, which are intermediate in magnitude between those in lower and higher energy region reported by other groups. A sharp decreasing of the Fermi contact interaction constant was found in 16 200-16 600 cm-1, and it may be caused by the interaction with the dark C ˜ 2A2 state. The hyperfine interaction constants are powerful clues to obtain reliable vibronic assignment. We tentatively assigned vibronic bands located at 14 836 cm-1, 15 586 cm-1, and 16 322 cm-1 as the transitions to the intrinsic (0,7,0), (0,8,0), and (0,9,0) vibrational levels of the à 2B2 state, respectively.

ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein-protein interactions with HPRT1.

PubMed

Vasiliou, Vasilis; Sandoval, Monica; Backos, Donald S; Jackson, Brian C; Chen, Ying; Reigan, Philip; Lanaspa, Miguel A; Johnson, Richard J; Koppaka, Vindhya; Thompson, David C

2013-02-25

Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A1*2, to be associated with gout and serum uric acid levels. ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures. ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants. In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1_v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines. The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains. The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs. Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout. Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1*2. These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1*2 carriers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

ALDH16A1 is a novel non-catalytic enzyme that may be involved in the etiology of gout via protein–protein interactions with HPRT1

PubMed Central

Vasiliou, Vasilis; Sandoval, Monica; Backos, Donald S.; Jackson, Brian C.; Chen, Ying; Reigan, Philip; Lanaspa, Miguel A.; Johnson, Richard J.; Koppaka, Vindhya; Thompson, David C.

2013-01-01

Gout, a common form of inflammatory arthritis, is strongly associated with elevated uric acid concentrations in the blood (hyperuricemia). A recent study in Icelanders identified a rare missense single nucleotide polymorphism (SNP) in the ALDH16A1 gene, ALDH16A1*2, to be associated with gout and serum uric acid levels. ALDH16A1 is a novel and rather unique member of the ALDH superfamily in relation to its gene and protein structures. ALDH16 genes are present in fish, amphibians, protista, bacteria but absent from archaea, fungi and plants. In most mammalian species, two ALDH16A1 spliced variants (ALDH16A1, long form and ALDH16A1_v2, short form) have been identified and both are expressed in HepG-2, HK-2 and HK-293 human cell lines. The ALDH16 proteins contain two ALDH domains (as opposed to one in the other members of the superfamily), four transmembrane and one coiled-coil domains. The active site of ALDH16 proteins from bacterial, frog and lower animals contain the catalytically important cysteine residue (Cys-302); this residue is absent from the mammalian and fish orthologs. Molecular modeling predicts that both the short and long forms of human ALDH16A1 protein would lack catalytic activity but may interact with the hypoxanthine-guanine phosphoribosyltransferase (HPRT1) protein, a key enzyme involved in uric acid metabolism and gout. Interestingly, such protein-protein interactions with HPRT1 are predicted to be impaired for the long or short forms of ALDH16A1*2. These results lead to the intriguing possibility that association between ALDH16A1 and HPRT1 may be required for optimal HPRT activity with disruption of this interaction possibly contributing to the hyperuricemia seen in ALDH16A1*2 carriers. PMID:23348497

Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects.

PubMed

Zhang, Xuan; Li, Honglin; Zhang, Huiran; Liu, Yani; Huo, Lifang; Jia, Zhanfeng; Xue, Yucong; Sun, Xiaorun; Zhang, Wei

2017-07-01

Natural flavonoids are ubiquitous in dietary plants and vegetables and have been proposed to have antiviral, antioxidant, cardiovascular protective and anticancer effects. Transmembrane member 16A (TMEM16A)-encoded Ca 2+ -activated Cl - channels play a variety of physiological roles in many organs and tissues. Overexpression of TMEM16A is also believed to be associated with cancer progression. Therefore, inhibition of TMEM16A current may be a potential target for cancer therapy. In this study, we screened a broad spectrum of flavonoids for their inhibitory activities on TMEM16A currents. A whole-cell patch technique was used to record the currents. The BrdU assay and transwell technique were used to investigate cell proliferation and migration. At a concentration of 100 μM, 10 of 20 compounds caused significant (>50%) inhibition of TMEM16A currents. The four most potent compounds - luteolin, galangin, quercetin and fisetin - had IC 50 values ranging from 4.5 to 15 μM). To examine the physiological relevance of these findings, we also studied the effects of these flavonoids on endogenous TMEM16A currents in addition to cell proliferation and migration in LA795 cancer cells. Among the flavonoids tested, we detected a highly significant correlation between TMEM16A current inhibition and cell proliferation or reduction of migration. This study demonstrates that flavonoids inhibit TMEM16A currents and suggests that flavonoids could have anticancer effects via this mechanism. © 2017 The British Pharmacological Society.

TMEM16A is associated with voltage-gated calcium channels in mouse retina and its function is disrupted upon mutation of the auxiliary α2δ4 subunit

PubMed Central

Caputo, Antonella; Piano, Ilaria; Demontis, Gian Carlo; Bacchi, Niccolò; Casarosa, Simona; Santina, Luca Della; Gargini, Claudia

2015-01-01

Photoreceptors rely upon highly specialized synapses to efficiently transmit signals to multiple postsynaptic targets. Calcium influx in the presynaptic terminal is mediated by voltage-gated calcium channels (VGCC). This event triggers neurotransmitter release, but also gates calcium-activated chloride channels (TMEM), which in turn regulate VGCC activity. In order to investigate the relationship between VGCC and TMEM channels, we analyzed the retina of wild type (WT) and Cacna2d4 mutant mice, in which the VGCC auxiliary α2δ4 subunit carries a nonsense mutation, disrupting the normal channel function. Synaptic terminals of mutant photoreceptors are disarranged and synaptic proteins as well as TMEM16A channels lose their characteristic localization. In parallel, calcium-activated chloride currents are impaired in rods, despite unaltered TMEM16A protein levels. Co-immunoprecipitation revealed the interaction between VGCC and TMEM16A channels in the retina. Heterologous expression of these channels in tsA-201 cells showed that TMEM16A associates with the CaV1.4 subunit, and the association persists upon expression of the mutant α2δ4 subunit. Collectively, our experiments show association between TMEM16A and the α1 subunit of VGCC. Close proximity of these channels allows optimal function of the photoreceptor synaptic terminal under physiological conditions, but also makes TMEM16A channels susceptible to changes occurring to calcium channels. PMID:26557056

γ-decay of {}_{8}^{16}{{\\rm{O}}}_{8}\\,{and}\\,{}_{7}^{16}{{\\rm{N}}}_{9} in proton-neutron Tamm-Dancoff and random phase approximations with optimized surface δ interaction

NASA Astrophysics Data System (ADS)

Pahlavani, M. R.; Firoozi, B.

2016-09-01

γ-ray transitions from excited states of {}16{{N}} and {}16{{O}} isomers that appear in the γ spectrum of the {}616{{{C}}}10\\to {}716{{{N}}}9\\to {}816{{{O}}}8 beta decay chain are investigated. The theoretical approach used in this research starts with a mean-field potential consisting of a phenomenological Woods-Saxon potential including spin-orbit and Coulomb terms (for protons) in order to obtain single-particle energies and wave functions for nucleons in a nucleus. A schematic residual surface delta interaction is then employed on the top of the mean field and is treated within the proton-neutron Tamm-Dancoff approximation (pnTDA) and the proton-neutron random phase approximation. The goal is to use an optimized surface delta interaction interaction, as a residual interaction, to improve the results. We have used artificial intelligence algorithms to establish a good agreement between theoretical and experimental energy spectra. The final results of the ‘optimized’ calculations are reasonable via this approach.

Magnetocardiogram measured by fundamental mode orthogonal fluxgate array

NASA Astrophysics Data System (ADS)

Karo, Hikaru; Sasada, Ichiro

2015-05-01

Magnetocardiography (MCG) of healthy volunteers has been measured by using a fundamental mode orthogonal fluxgate magnetometer array of 32 channels in a magnetic shielded room (MSR). Sensor heads, which are employed, consist of a 45 mm long U-shaped amorphous wire core and a 1000-turn solenoid pick-up coil of 30 mm in length and 3 mm in outer diameter. The excitation current of 100 kHz with large dc bias current is fed directly into wire cores, which are connected in series, whereas the signal detection circuit is provided to each of the sensor heads. A special technique to avoid mutual interaction between sensor heads is implemented, where all the sensor heads are excited synchronously by using a single ac source. A 2-D array having 32 sensors with 4 cm grid spacing was used to measure MCG signals inside an MSR. Measured data from each channel were first filtered (0.16-100 Hz pass band), then averaged for 2 min synchronously with electrocardiogram's peaks taken from both hands. Noise remaining after the average is about 1.8 pTrms for the band-width of 0.16-100 Hz. The QRS complex and the T-wave are clearly detected.

Site-directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16.

PubMed

Petit, Sarah J; Chayen, Naomi E; Pease, James E

2008-08-01

Chemokine receptor CXCR6 mediates the chemotaxis and adhesion of leukocytes to soluble and membrane-anchored forms of CXCL16, and is an HIV-1 co-receptor. Here, we describe the effects of mutation of acidic extracellular CXCR6 residues on receptor function. Although most CXCR6 mutants examined were expressed at levels similar to wild-type (WT) CXCR6, an N-terminal E3Q mutant was poorly expressed, which may explain previously reported protective effects of a similar single nucleotide polymorphism, with respect to late-stage HIV-1 infection. In contrast to several other chemokine receptors, mutation of the CXCR6 N terminus and inhibition of post-translational modifications of this region were without effect on receptor function. Likewise, N-terminal extension of CXCL16 resulted in a protein with decent potency and efficacy in chemotaxis and not, as anticipated, a CXCR6 antagonist. D176N and E274Q CXCR6 mutants were unable to interact with soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding. Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant could promote robust adhesion to membrane-anchored CXCL16, suggesting that soluble and membrane-bound forms of CXCL16 possess distinct conformations. Collectively, our data suggest a novel paradigm for the CXCR6:CXCL16 interaction, a finding which may impact the discovery of small-molecule antagonists of CXCR6.

Molecular Mapping of the RNA Cap 2′-O-Methyltransferase Activation Interface between Severe Acute Respiratory Syndrome Coronavirus nsp10 and nsp16*

PubMed Central

Lugari, Adrien; Betzi, Stephane; Decroly, Etienne; Bonnaud, Emmanuel; Hermant, Aurélie; Guillemot, Jean-Claude; Debarnot, Claire; Borg, Jean-Paul; Bouvet, Mickaël; Canard, Bruno; Morelli, Xavier; Lécine, Patrick

2010-01-01

Several protein-protein interactions within the SARS-CoV proteome have been identified, one of them being between non-structural proteins nsp10 and nsp16. In this work, we have mapped key residues on the nsp10 surface involved in this interaction. Alanine-scanning mutagenesis, bioinformatics, and molecular modeling were used to identify several “hot spots,” such as Val42, Met44, Ala71, Lys93, Gly94, and Tyr96, forming a continuous protein-protein surface of about 830 Å2, bearing very conserved amino acids among coronaviruses. Because nsp16 carries RNA cap 2′-O-methyltransferase (2′O-MTase) activity only in the presence of its interacting partner nsp10 (Bouvet, M., Debarnot, C., Imbert, I., Selisko, B., Snijder, E. J., Canard, B., and Decroly, E. (2010) PLoS Pathog. 6, e1000863), functional consequences of mutations on this surface were evaluated biochemically. Most changes that disrupted the nsp10-nsp16 interaction without structural perturbations were shown to abrogate stimulation of nsp16 RNA cap 2′O-MTase activity. More strikingly, the Y96A mutation abrogates stimulation of nsp16 2′O-MTase activity, whereas Y96F overstimulates it. Thus, the nsp10-nsp16 interface may represent an attractive target for antivirals against human and animal pathogenic coronaviruses. PMID:20699222

High-current, relativistic electron-beam transport in metals and the role of magnetic collimation.

PubMed

Storm, M; Solodov, A A; Myatt, J F; Meyerhofer, D D; Stoeckl, C; Mileham, C; Betti, R; Nilson, P M; Sangster, T C; Theobald, W; Guo, Chunlei

2009-06-12

High-resolution coherent transition radiation (CTR) imaging diagnoses electrons accelerated in laser-solid interactions with intensities of approximately 10;{19} W/cm;{2}. The CTR images indicate electron-beam filamentation and annular propagation. The beam temperature and half-angle divergence are inferred to be approximately 1.4 MeV and approximately 16 degrees , respectively. Three-dimensional hybrid-particle-in-cell code simulations reproduce the details of the CTR images assuming an initial half-angle divergence of approximately 56 degrees . Self-generated resistive magnetic fields are responsible for the difference between the initial and measured divergence.

Enhanced emotion-induced amnesia in borderline personality disorder

PubMed Central

HURLEMANN, RENÉ; HAWELLEK, BARBARA; MAIER, WOLFGANG; DOLAN, RAYMOND J.

2009-01-01

Background Current biological concepts of borderline personality disorder (BPD) emphasize the interference of emotional hyperarousal and cognitive functions. A prototypical example is episodic memory. Pre-clinical investigations of emotion–episodic memory interactions have shown specific retrograde and anterograde episodic memory changes in response to emotional stimuli. These changes are amygdala dependent and vary as a function of emotional arousal and valence. Method To determine whether there is amygdala hyper-responsiveness to emotional stimuli as the underlying pathological substrate of cognitive dysfunction in BPD, 16 unmedicated female patients with BPD were tested on the behavioural indices of emotion-induced amnesia and hypermnesia established in 16 healthy controls. Results BPD patients displayed enhanced retrograde and anterograde amnesia in response to presentation of negative stimuli, while positive stimuli elicited no episodic memory-modulating effects. Conclusion These findings suggest that an amygdala hyper-responsiveness to negative stimuli may serve as a crucial aetiological contributor to emotion-induced cognitive dysfunction in BPD. PMID:17224096

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

Nesterov, V. A., E-mail: archerix@ukpost.ua

On the basis of the energy-density method, the effect of simultaneously taking into account the Pauli exclusion principle and the monopole and quadrupole polarizations of interacting nuclei on their interaction potential is considered for the example of the {sup 16}O + {sup 16}O system by using the wave function for the two-center shell model. The calculations performed in the adiabatic approximation reveal that the inclusion of the Pauli exclusion principle and the polarization of interacting nuclei, especially their quadrupole polarization, has a substantial effect on the potential of the nucleus-nucleus interaction.

Forces between Two Glass Surfaces with Adsorbed Hexadecyltrimethylammonium Salicylate.

PubMed

Imae, T; Kato, M; Rutland, M

2000-02-22

Forces have been measured for hexadecyltrimethylammonium salicylate (C(16)TASal) layers on glass beads. During the inward process, hydrophobic attraction occurred at lower adsorption of C(16)TASal and electrostatic repulsion interactions happened at higher adsorption. While the jump-in phenomenon was observed for solutions of concentrations below the critical micelle concentration (cmc = 0.15 mM), the step-in phenomenon was characteristic for solutions at the cmc and above the cmc, suggesting the push-out of adsorbed C(16)TASal layers and/or inserted micelles. The remarkable pull-off phenomenon on the outward process occurred for all solutions, indicating a strong interaction between C(16)TASal molecules. For aqueous 0.15 mM C(16)TASal solutions of various NaSal concentrations, on the inward process, the electrostatic repulsive interaction decreased with adding NaSal. This is due to the electrostatic shielding by salt excess. The height of the force wall on the inward process reached a maximum at 0.01 M NaSal, but the interlocking between molecules on two surfaces during the outward process was minimized at 0.1 M NaSal. These tendencies, which are different from that of the electrostatic repulsion interaction, imply the strong cohesion between adsorbed C(16)TASal layers.

The Transcription Factors TBX2 and TBX3 Interact with Human Papillomavirus 16 (HPV16) L2 and Repress the Long Control Region of HPVs

PubMed Central

Schneider, Marc A.; Scheffer, Konstanze D.; Bund, Timo; Boukhallouk, Fatima; Lambert, Carsten; Cotarelo, Cristina; Pflugfelder, Gert O.

2013-01-01

The minor capsid protein L2 of human papillomaviruses (HPVs) has multiple functions during the viral life cycle. Although L2 is required for effective invasion and morphogenesis, only a few cellular interaction partners are known so far. Using yeast two-hybrid screening, we identified the transcription factor TBX2 as a novel interaction partner of HPV type 16 (HPV16) L2. Coimmunoprecipitations and immunofluorescence analyses confirmed the L2-TBX2 interaction and revealed that L2 also interacts with TBX3, another member of the T-box family. Transcription of the early genes during HPV infection is under the control of an upstream enhancer and early promoter region, the long control region (LCR). In promoter-reporter gene assays, we observed that TBX2 and TBX3 repress transcription from the LCR and that this effect is enhanced by L2. Repression of the HPV LCR by TBX2/3 seems to be a conserved mechanism, as it was also observed with the LCRs of different HPV types. Finally, interaction of TBX2 with the LCR was detected by chromatin immunoprecipitation, and we found a strong colocalization of L2 and TBX2 in HPV16-positive cervical intraepithelial neoplasia (CIN) I-II tissue sections. These results suggest that TBX2/3 might play a role in the regulation of HPV gene expression during the viral life cycle. PMID:23388722

In silico identification of essential proteins in Corynebacterium pseudotuberculosis based on protein-protein interaction networks.

PubMed

Folador, Edson Luiz; de Carvalho, Paulo Vinícius Sanches Daltro; Silva, Wanderson Marques; Ferreira, Rafaela Salgado; Silva, Artur; Gromiha, Michael; Ghosh, Preetam; Barh, Debmalya; Azevedo, Vasco; Röttger, Richard

2016-11-04

Corynebacterium pseudotuberculosis (Cp) is a gram-positive bacterium that is classified into equi and ovis serovars. The serovar ovis is the etiological agent of caseous lymphadenitis, a chronic infection affecting sheep and goats, causing economic losses due to carcass condemnation and decreased production of meat, wool, and milk. Current diagnosis or treatment protocols are not fully effective and, thus, require further research of Cp pathogenesis. Here, we mapped known protein-protein interactions (PPI) from various species to nine Cp strains to reconstruct parts of the potential Cp interactome and to identify potentially essential proteins serving as putative drug targets. On average, we predict 16,669 interactions for each of the nine strains (with 15,495 interactions shared among all strains). An in silico sanity check suggests that the potential networks were not formed by spurious interactions but have a strong biological bias. With the inferred Cp networks we identify 181 essential proteins, among which 41 are non-host homologous. The list of candidate interactions of the Cp strains lay the basis for developing novel hypotheses and designing according wet-lab studies. The non-host homologous essential proteins are attractive targets for therapeutic and diagnostic proposes. They allow for searching of small molecule inhibitors of binding interactions enabling modern drug discovery. Overall, the predicted Cp PPI networks form a valuable and versatile tool for researchers interested in Corynebacterium pseudotuberculosis.

Monitoring HPV-16 E7 phosphorylation events

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

Nogueira, Marcela O.; Hošek, Tomáš; Calçada, Eduar

HPV-16 E7 is one of the key proteins that, by interfering with the host metabolism through many protein-protein interactions, hijacks cell regulation and contributes to malignancy. Here we report the high resolution investigation of the CR3 region of HPV-16 E7, both as an isolated domain and in the full-length protein. This opens the way to the atomic level study of the many interactions in which HPV-16 E7 is involved. Along these lines we show here the effect of one of the key post-translational modifications of HPV-16 E7, the phosphorylation by casein kinase II.

delta 9-(16 alpha-/sup 125/I)iodo-19-nortestosterone: a gamma-emitting photoaffinity label for the progesterone receptor

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

Lamb, D.J.; Bullock, D.W.; Hoyte, R.M.

1988-05-01

We have synthesized 16 alpha-iodo-4,9-estradien-17 beta-ol-3-one (delta 9-16 alpha-iodo-19-nortestosterone (delta 9-INT)) labeled with 125I (delta 9-(16 alpha-125I)INT) to provide a new gamma-emitting photoaffinity ligand for the progesterone receptor that has many advantages over the currently available (3H)R5020. We have characterized the interaction of delta 9-(16 alpha-125I)INT with the rabbit uterine progesterone receptor and have demonstrated the usefulness of this compound for studies of receptor structure. The binding of 2 nM (3H)progesterone to receptor in rabbit uterine cytosol was specifically competed for by 19-nortestosterone, 16 alpha-iodo-19-nortestosterone, and delta 9-INT. Scatchard analysis demonstrated that delta 9-(16 alpha-125I)INT and (3H)progesterone estimated the samemore » number of binding sites in rabbit uterine cytosol, with a Kd for delta 9-(16 alpha-125I)INT of about 2.7 nM. The binding of delta 9-(16 alpha-125I)INT was inhibited by both progesterone and R5020, whereas testosterone, estradiol, and 5 alpha-dihydrotestosterone were ineffective. In cytosol, delta 9-(16 alpha-125I)INT covalently labeled the same mol wt receptor forms as (3H)R5020. Although the efficiency of cross-linking was similar for (3H)R5020 (3%) and delta 9-(16 alpha-125I)INT (4%), the radioactivity was 10-fold greater due to the higher specific activity of delta 9-(16 alpha-125I)INT and the lack of sample quench. The use of delta 9-(16 alpha-125I)INT greatly increases the sensitivity and efficiency of the photoaffinity labeling technique; it will provide a valuable tool for further studies of the progesterone receptor, allowing the detection of receptor in dilute cytosol after gel electrophoresis under denaturing conditions.« less

Properties of Nuclei up to A = 16 using Local Chiral Interactions

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

Lonardoni, Diego; Carlson, Joseph; Gandolfi, Stefano

Here, we report accurate quantum Monte Carlo calculations of nuclei up to A = 16 based on local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We examine the theoretical uncertainties associated with the chiral expansion and the cutoff in the theory, as well as the associated operator choices in the three-nucleon interactions. While in light nuclei the cutoff variation and systematic uncertainties are rather small, in 16O these can be significant for large coordinate-space cutoffs. Overall, we show that chiral interactions constructed to reproduce properties of very light systems and nucleon-nucleon scattering give an excellent description of bindingmore » energies, charge radii, and form factors for all these nuclei, including open-shell systems in A = 6 and 12.« less

Properties of Nuclei up to A = 16 using Local Chiral Interactions

DOE PAGES

Lonardoni, Diego; Carlson, Joseph; Gandolfi, Stefano; ...

2018-03-22

Here, we report accurate quantum Monte Carlo calculations of nuclei up to A = 16 based on local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We examine the theoretical uncertainties associated with the chiral expansion and the cutoff in the theory, as well as the associated operator choices in the three-nucleon interactions. While in light nuclei the cutoff variation and systematic uncertainties are rather small, in 16O these can be significant for large coordinate-space cutoffs. Overall, we show that chiral interactions constructed to reproduce properties of very light systems and nucleon-nucleon scattering give an excellent description of bindingmore » energies, charge radii, and form factors for all these nuclei, including open-shell systems in A = 6 and 12.« less

Characterization of Convective Boiling in Branching Channel Heat Sinks

DTIC Science & Technology

2009-05-06

pressure drop was well predicted using the void fraction correlation of Zivi [11] and the phase interaction parameter of Qu and Mudawar [16]. Model...paper number HT2008-56253, ASME Heat Transfer Summer Conference, August 10-14, 2008, Jacksonville, FL. 16. W. Qu, I. Mudawar , Measurement and...level. The Zivi [11] correlation is also recommended, with the two-phase interaction parameter of Qu and Mudawar [16] for use in the one-dimensional

Ocean dynamics studies. [of current-wave interactions

NASA Technical Reports Server (NTRS)

1974-01-01

Both the theoretical and experimental investigations into current-wave interactions are discussed. The following three problems were studied: (1) the dispersive relation of a random gravity-capillary wave field; (2) the changes of the statistical properties of surface waves under the influence of currents; and (3) the interaction of capillary-gravity with the nonuniform currents. Wave current interaction was measured and the feasibility of using such measurements for remote sensing of surface currents was considered. A laser probe was developed to measure the surface statistics, and the possibility of using current-wave interaction as a means of current measurement was demonstrated.

Globalization of healthcare.

PubMed

2012-05-01

Globalization-the increasing transnational circulation of money, goods, people, ideas, and information worldwide-is generally recognized as one of the most powerful forces shaping our current and future history. How is it affecting healthcare, and in that context, what is the purpose and significance of Global Advances in Health and Medicine (GAHM), publisher of this journal? Our goal is not homogenization but rather to provide an opportunity for integration, convergence, and collaboration across cultures. By respecting and conserving the richness and diversity of each new medicine, we embrace globalization. Globalization is of course not new; it began in the Renaissance and particularly with the 15th- and 16th-century voyages of exploration by Columbus, Magellan, and others. Since the beginning of time, there have been interactions and exchanges among different peoples and cultures. However, the current magnitude of globalization is unprecedented and yet still expanding rapidly.

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

PubMed Central

Kim, Hyung-Goo; Kishikawa, Shotaro; Higgins, Anne W.; Seong, Ihn-Sik; Donovan, Diana J.; Shen, Yiping; Lally, Eric; Weiss, Lauren A.; Najm, Juliane; Kutsche, Kerstin; Descartes, Maria; Holt, Lynn; Braddock, Stephen; Troxell, Robin; Kaplan, Lee; Volkmar, Fred; Klin, Ami; Tsatsanis, Katherine; Harris, David J.; Noens, Ilse; Pauls, David L.; Daly, Mark J.; MacDonald, Marcy E.; Morton, Cynthia C.; Quade, Bradley J.; Gusella, James F.

2008-01-01

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of α-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs ∼750 kb 5′ to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the α-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD. PMID:18179900

Novel Interactions Identified between μ-Conotoxin and the Na+ Channel Domain I P-loop: Implications for Toxin-Pore Binding Geometry

PubMed Central

Xue, Tian; Ennis, Irene L.; Sato, Kazuki; French, Robert J.; Li, Ronald A.

2003-01-01

μ-Conotoxins (μ-CTX) are peptides that inhibit Na+ flux by blocking the Na+ channel pore. Toxin residue arginine 13 is critical for both high affinity binding and for complete block of the single channel current, prompting the simple conventional view that residue 13 (R13) leads toxin docking by entering the channel along the pore axis. To date, the strongest interactions identified are between μ-CTX and domain II (DII) or DIII pore residues of the rat skeletal muscle (Nav1.4) Na+ channels, but little data is available for the role of the DI P-loop in μ-CTX binding due to the lack of critical determinants identified in this domain. Despite being an essential determinant of isoform-specific tetrodotoxin sensitivity, the DI-Y401C variant had little effect on μ-CTX block. Here we report that the charge-changing substitution Y401K dramatically reduced the μ-CTX affinity (∼300-fold). Using mutant cycle analysis, we demonstrate that K401 couples strongly to R13 (ΔΔG > 3.0 kcal/mol) but not R1, K11, or R14 (≪1 kcal/mol). Unlike K401, however, a significant coupling was detected between toxin residue 14 and DI-E403K (ΔΔG = 1.4 kcal/mol for the E403K-Q14D pair). This appears to underlie the ability of DI-E403K channels to discriminate between the GIIIA and GIIIB isoforms of μ-CTX (p < 0.05), whereas Y401K, DII-E758Q, and DIII-D1241K do not. We also identify five additional, novel toxin-channel interactions (>0.75 kcal/mol) in DII (E758-K16, D762-R13, D762-K16, E765-R13, E765-K16). Considered together, these new interactions suggest that the R13 side chain and the bulk of the bound toxin μ-CTX molecule may be significantly tilted with respect to pore axis. PMID:14507694

WE-C-217BCD-10: Development of High Performance PET for Animal Imaging and Therapy Applications.

PubMed

Shao, Y; Sun, X; Lan, K; Bircher, C

2012-06-01

A prototype small animal PET is developed with several novel technologies to measure 3D gamma-interaction positions and to substantially improve imaging performance. Each new detector has an 8×8 array of 1.95×1.95×30 mm̂3 LYSO scintillators, with each end optically connected to a solid-state photo multiplier (SSPM) array through a light guide. This dual-ended-readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has 16 SSPMs arranged in a 4×4 matrix. Each SSPM has active area about 3×3 mm̂2, with its output read by an ASIC electronics that directly converts analog signals to digital timing pulses which encode the interaction information for energy, timing, crystal of interaction, and DOI calculations. These digital pulses are transferred to and decoded by FPGA-based TDC for coincident event selection and data acquisition. This independent readout of each SSPM and parallel signal process significantly improve signal-to-noise ratio and permit applying flexible data processing algorithms. The current prototype system consists of two rotating detector panels on a portable gantry, with 4 detectors linearly packed together in each panel to provide ∼16 mm axial and variable trans- axial FOV with adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction with resolution modeling was implemented. Both Na- 22 point source and phantom were used to evaluate the system performance. The measured energy, timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0 mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ∼1.7 mm across the entire FOV in all direction, while those without DOI were much worse and non-uniform across the FOV, in the range predominately around 3.0 to 4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show significantly improved quality compared to those without DOI. DOI- measurable PET shows substantially improved image performance for a compact system. National Institute of Health. University of Texas MD Anderson Cancer Center. © 2012 American Association of Physicists in Medicine.

Human Papillomavirus 16 Infection Induces VAP-Dependent Endosomal Tubulation.

PubMed

Siddiqa, Abida; Massimi, Paola; Pim, David; Broniarczyk, Justyna; Banks, Lawrence

2018-03-15

Human papillomavirus (HPV) infection involves complex interactions with the endocytic transport machinery, which ultimately facilitates the entry of the incoming viral genomes into the trans -Golgi network (TGN) and their subsequent nuclear entry during mitosis. The endosomal pathway is a highly dynamic intracellular transport system, which consists of vesicular compartments and tubular extensions, although it is currently unclear whether incoming viruses specifically alter the endocytic machinery. In this study, using MICAL-L1 as a marker for tubulating endosomes, we show that incoming HPV-16 virions induce a profound alteration in global levels of endocytic tubulation. In addition, we also show a critical requirement for the endoplasmic reticulum (ER)-anchored protein VAP in this process. VAP plays an essential role in actin nucleation and endosome-to-Golgi transport. Indeed, the loss of VAP results in a dramatic decrease in the level of endosomal tubulation induced by incoming HPV-16 virions. This is also accompanied by a marked reduction in virus infectivity. In VAP knockdown cells, we see that the defect in virus trafficking occurs after capsid disassembly but prior to localization at the trans -Golgi network, with the incoming virion-transduced DNA accumulating in Vps29/TGN46-positive hybrid vesicles. Taken together, these studies demonstrate that infection with HPV-16 virions induces marked alterations of endocytic transport pathways, some of which are VAP dependent and required for the endosome-to-Golgi transport of the incoming viral L2/DNA complex. IMPORTANCE Human papillomavirus infectious entry involves multiple interactions with the endocytic transport machinery. In this study, we show that incoming HPV-16 virions induce a dramatic increase in endocytic tubulation. This tubulation requires ER-associated VAP, which plays a critical role in ensuring the delivery of cargoes from the endocytic compartments to the trans -Golgi network. Indeed, the loss of VAP blocks HPV infectious entry at a step after capsid uncoating but prior to localization at the trans -Golgi network. These results define a critical role for ER-associated VAP in endocytic tubulation and in HPV-16 infectious entry. Copyright © 2018 American Society for Microbiology.

Predicting Microbial Fuel Cell Biofilm Communities and Bioreactor Performance using Artificial Neural Networks.

PubMed

Lesnik, Keaton Larson; Liu, Hong

2017-09-19

The complex interactions that occur in mixed-species bioelectrochemical reactors, like microbial fuel cells (MFCs), make accurate predictions of performance outcomes under untested conditions difficult. While direct correlations between any individual waste stream characteristic or microbial community structure and reactor performance have not been able to be directly established, the increase in sequencing data and readily available computational power enables the development of alternate approaches. In the current study, 33 MFCs were evaluated under a range of conditions including eight separate substrates and three different wastewaters. Artificial Neural Networks (ANNs) were used to establish mathematical relationships between wastewater/solution characteristics, biofilm communities, and reactor performance. ANN models that incorporated biotic interactions predicted reactor performance outcomes more accurately than those that did not. The average percent error of power density predictions was 16.01 ± 4.35%, while the average percent error of Coulombic efficiency and COD removal rate predictions were 1.77 ± 0.57% and 4.07 ± 1.06%, respectively. Predictions of power density improved to within 5.76 ± 3.16% percent error through classifying taxonomic data at the family versus class level. Results suggest that the microbial communities and performance of bioelectrochemical systems can be accurately predicted using data-mining, machine-learning techniques.

On the local injection of emitted electrons into micrograins on the surface of A{sup III}–B{sup V} semiconductors

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

Zhukov, N. D., E-mail: ndzhukov@rambler.ru; Glukhovskoi, E. G.; Khazanov, A. A.

2016-06-15

The characteristics of the injection of electrons into a semiconductor from a microprobe–micrograin nanogap are investigated with a tunneling microscope in the mode of field emission into locally selected surface microcrystals of indium antimonide, indium arsenide, and gallium arsenide. The current mechanisms are established and their parameters are determined by comparing the experimental I–V characteristics and those calculated from formulas of current transport. The effect of limitation of the current into the micrograins of indium antimonide and indium arsenide which manifests itself at injection levels exceeding a certain critical value, e.g., 6 × 10{sup 16} cm{sup –3} for indium antimonidemore » and 4 × 10{sup 17} cm{sup –3} for indium arsenide, is discovered. A physical model, i.e., the localization of electrons in the surface area of a micrograin due to their Coulomb interaction, is proposed.« less

Interactive introductory nutrition course focusing on disease prevention increased whole-grain consumption by college students.

PubMed

Ha, Eun-Jeong; Caine-Bish, Natalie

2011-01-01

To estimate current consumption of whole grains in college students and determine whether there would be an increase in whole-grain consumption after the students completed an interactive introductory nutrition course focusing on disease prevention. Eighty college students, 18-24 years old, participated in the study. Grain and whole-grain consumption, whole-grain food sources, and energy intake were measured before and after the nutrition course. Repeated-measures analysis of variance was performed. After the study, whole-grain intake significantly increased from 0.37 ounces (oz) to 1.16 oz (P < .001), whereas total grain intake remained the same (3.07 oz). The number of whole-grain food sources increased from 7 to 11 food items after the intervention. A general nutrition course can be used as an avenue to increase whole-grain intake by college students. Copyright © 2011 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Interactions of 2.1 GeV/n He-4, C-12, N-14 and O-16 nuclei in emulsion

NASA Technical Reports Server (NTRS)

Heckman, H. H.; Greiner, D. E.; Lindstrom, P. J.; Shwe, H.

1975-01-01

The interaction mean-free-path lengths for He-4, C-12, N-14 and O-16 nuclei at 2.1 GeV/n have been measured in nuclear emulsion detectors. The angular distributions of Z equals 1 and 2 secondaries from the interactions of C, N and O beams are determined, and the topology of projectile fragmentation of these ions is examined.

Unraveling the interaction of hemoglobin with a biocompatible and cleavable oxy-diester-functionalized gemini surfactant.

PubMed

Akram, Mohd; Anwar, Sana; Bhat, Imtiyaz Ahmad; Kabir-Ud-Din

2017-03-01

Surfactant-protein mixtures have attracted considerable research interest in recent years at the interface of chemical biology and medicinal chemistry. Herein, the interaction between a green gemini surfactant (C 16 -E2O-C 16 ) and a redox protein hemoglobin was examined through a series of in vitro experimental techniques with an attempt to provide a comprehensive knowledge of the surfactant-protein binding interactions. Quantitative appraisal of the fluorescence/CV data showed that the binding of C 16 -E2O-C 16 to Hb leads to the formation of thermodynamically favorable non-covalent adduct with 1:1 stoichiometry. UV-vis spectra demonstrated that the effect of C 16 -E2O-C 16 on Hb is highly concentration dependent. Far-UV and near-UV CD spectra together elucidated the formation of molten globule state of Hb upon C 16 -E2O-C 16 addition. Temperature dependent CD explicated the effect of C 16 -E2O-C 16 on the thermal stability of Hb. Furthermore, the structural investigation of Hb via pyrene/synchronous/three-dimensional fluorescence and FT-IR spectroscopy provided the complementary information related to its microenvironmental and conformational changes. Computational studies delineated that C 16 -E2O-C 16 binds in the vicinity of β-37 Trp at the α 1 β 2 interface of Hb. Overall, this study is expected to clarify the binding mechanism between Hb/other congeners and surfactant at the molecular level that are known to have immense potential in biomedical and industrial areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Lunar electrical conductivity, permeability and temperature from Apollo magnetometer experiments

NASA Technical Reports Server (NTRS)

Dyal, P.; Parkin, C. W.; Daily, W. D.

1977-01-01

Magnetometers were deployed at four Apollo sites on the moon to measure remanent and induced lunar magnetic fields. Measurements from this network of instruments were used to calculate the electrical conductivity, temperature, magnetic permeability, and iron abundance of the lunar interior. The measured lunar remanent fields range from 3 gammas minimum at the Apollo 15 site to 327 gammas maximum at the Apollo 16 site. Simultaneous magnetic field and solar plasma pressure measurements show that the remanent fields at the Apollo 12 and 16 sites interact with, and are compressed by, the solar wind. Remanent fields at Apollo 12 and Apollo 16 are increased 16 gammas and 32 gammas, respectively, by a solar plasma bulk pressure increase of 1.5 X 10 to the -7th power dynes/sq cm. Global lunar fields due to eddy currents, induced in the lunar interior by magnetic transients, were analyzed to calculate an electrical conductivity profile for the moon. From nightside magnetometer data in the solar wind it was found that deeper than 170 km into the moon the conductivity rises from .0003 mhos/m to .10 mhos/m at 100 km depth. Recent analysis of data obtained in the geomagnetic tail, in regions free of complicating plasma effects, yields results consistent with nightside values.

Cooperative interaction among the various regulatory sites within the NMDA receptor-channel complex in modulating the evoked responses to noxious thermal stimuli of spinal dorsal horn neurons in the cat.

PubMed

Song, X J; Zhao, Z Q

1998-05-01

Interactions among antagonists acting at different regulatory sites within the N-methyl-D-aspartate (NMDA) receptor-channel complex on the evoked responses to noxious thermal stimuli of wide dynamic range (WDR) neurons in spinal dorsal horn were studied on 21 adult anesthetized and spinalized cats. The responses of nociceptive spinal dorsal horn neurons to noxious heating (45-55 degrees C) of the glabrous skin of the unilateral hind paw were reduced markedly by iontophoretically applied antagonists. The specific recognition site antagonist, DL-2-amino-5-phosphonovaleratic acid (APV), the strychnine-insensitive glycine site antagonist 7-chlorokynurenic acid (7CKA), the polyamine site antagonist ifenprodil (IFEN), and the phencyclidine (PCP) site antagonists ketamine (KET) and MK-801 (40-100 nA) significantly reduced (t-tests, P < 0.01) the noxious thermal stimulus-evoked responses in about 70% of the neurons by (mean +/- SE) 54.1 +/- 5.8% (n = 19), 80.8 +/- 4.7% (n = 16), 51.1 +/- 6.4% (n = 10), 77 +/- 4.9% (n = 16) and 81.2 +/- 8.1% (n = 5), respectively. APV and IFEN were less effective in blocking noxious thermal stimuli-evoked responses than 7CKA, KET and MK-801 (ANOVA, P < 0.05). The responses were completely inhibited in some neurons. After co-administration of the antagonists, APV + 7CKA, APV + IFEN, 7CKA + IFEN, APV + KET and APV + MK-801, all at the subthreshold ejection current, the responses were reduced markedly in 13 of 16, 7 of 10, 5 of 10, 3 of 6 and 3 of 5 neurons, respectively. The present study suggests that blockage of any component of the NMDA receptor-channel complex antagonizes the NMDA receptor-mediated response, and that there are the cooperative interactions among the various regulatory sites within the NMDA receptor-channel complex in the transmission or modulation of spinal nociceptive thermal information.

House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population

PubMed Central

Carnes, Megan Ulmer; Hoppin, Jane A.; Metwali, Nervana; Wyss, Annah B.; Hankinson, John L.; O’Connell, Elizabeth Long; Richards, Marie; Long, Stuart; Freeman, Laura E. Beane; Sandler, Dale P.; Henneberger, Paul K.; Barker-Cummings, Christie; Umbach, David M.; Thorne, Peter S.

2017-01-01

Rationale: Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations. Objectives: To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population. Methods: Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case–control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression. Measurements and Main Results: Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14–1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02–1.37; not born on a farm: OR, 1.67; 95% CI, 1.26–2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV1/FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791. Conclusions: House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma. PMID:27977294

Tamoxifen Inhibition of Kv7.2/Kv7.3 Channels

PubMed Central

Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S.; Tristani-Firouzi, Martin; Sanchez-Chapula, José A.

2013-01-01

KCNQ genes encode five Kv7 K+ channel subunits (Kv7.1–Kv7.5). Four of these (Kv7.2–Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels. PMID:24086693

Tamoxifen inhibition of kv7.2/kv7.3 channels.

PubMed

Ferrer, Tania; Aréchiga-Figueroa, Ivan Arael; Shapiro, Mark S; Tristani-Firouzi, Martin; Sanchez-Chapula, José A

2013-01-01

KCNQ genes encode five Kv7 K(+) channel subunits (Kv7.1-Kv7.5). Four of these (Kv7.2-Kv7.5) are expressed in the nervous system. Kv7.2 and Kv7.3 are the principal molecular components of the slow voltage-gated M-channel, which regulates neuronal excitability. In this study, we demonstrate that tamoxifen, an estrogen receptor antagonist used in the treatment of breast cancer, inhibits Kv7.2/Kv7.3 currents heterologously expressed in human embryonic kidney HEK-293 cells. Current inhibition by tamoxifen was voltage independent but concentration-dependent. The IC50 for current inhibition was 1.68 ± 0.44 µM. The voltage-dependent activation of the channel was not modified. Tamoxifen inhibited Kv7.2 homomeric channels with a higher potency (IC50 = 0.74 ± 0.16 µM). The mutation Kv7.2 R463E increases phosphatidylinositol- 4,5-bisphosphate (PIP2) - channel interaction and diminished dramatically the inhibitory effect of tamoxifen compared with that for wild type Kv7.2. Conversely, the mutation Kv7.2 R463Q, which decreases PIP2 -channel interaction, increased tamoxifen potency. Similar results were obtained on the heteromeric Kv7.2 R463Q/Kv7.3 and Kv7.2 R463E/Kv7.3 channels, compared to Kv7.2/Kv7.3 WT. Overexpression of type 2A PI(4)P5-kinase (PIP5K 2A) significantly reduced tamoxifen inhibition of Kv7.2/Kv7.3 and Kv7.2 R463Q channels. Our results suggest that tamoxifen inhibited Kv7.2/Kv7.3 channels by interfering with PIP2-channel interaction because of its documented interaction with PIP2 and the similar effect of tamoxifen on various PIP2 sensitive channels.

Analysis of SLC16A11 Variants in 12,811 American Indians: Genotype-Obesity Interaction for Type 2 Diabetes and an Association With RNASEK Expression.

PubMed

Traurig, Michael; Hanson, Robert L; Marinelarena, Alejandra; Kobes, Sayuko; Piaggi, Paolo; Cole, Shelley; Curran, Joanne E; Blangero, John; Göring, Harald; Kumar, Satish; Nelson, Robert G; Howard, Barbara V; Knowler, William C; Baier, Leslie J; Bogardus, Clifton

2016-02-01

Genetic variants in SLC16A11 were recently reported to be associated with type 2 diabetes in Mexican and other Latin American populations. The diabetes risk haplotype had a frequency of 50% in Native Americans from Mexico but was rare in Europeans and Africans. In the current study, we analyzed SLC16A11 in 12,811 North American Indians and found that the diabetes risk haplotype, tagged by the rs75493593 A allele, was nominally associated with type 2 diabetes (P = 0.001, odds ratio 1.11). However, there was a strong interaction with BMI (P = 5.1 × 10(-7)) such that the diabetes association was stronger in leaner individuals. rs75493593 was also strongly associated with BMI in individuals with type 2 diabetes (P = 3.4 × 10(-15)) but not in individuals without diabetes (P = 0.77). Longitudinal analyses suggest that this is due, in part, to an association of the A allele with greater weight loss following diabetes onset (P = 0.02). Analyses of global gene expression data from adipose tissue, skeletal muscle, and whole blood provide evidence that rs75493593 is associated with expression of the nearby RNASEK gene, suggesting that RNASEK expression may mediate the effect of genotype on diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

20 CFR 1.6 - How were many of OWCP's current functions administered in the past?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false How were many of OWCP's current functions administered in the past? 1.6 Section 1.6 Employees' Benefits OFFICE OF WORKERS' COMPENSATION PROGRAMS, DEPARTMENT OF LABOR ORGANIZATION AND PROCEDURES PERFORMANCE OF FUNCTIONS § 1.6 How were many of OWCP's...

SELMAP - SELEX affinity landscape MAPping of transcription factor binding sites using integrated microfluidics

PubMed Central

Chen, Dana; Orenstein, Yaron; Golodnitsky, Rada; Pellach, Michal; Avrahami, Dorit; Wachtel, Chaim; Ovadia-Shochat, Avital; Shir-Shapira, Hila; Kedmi, Adi; Juven-Gershon, Tamar; Shamir, Ron; Gerber, Doron

2016-01-01

Transcription factors (TFs) alter gene expression in response to changes in the environment through sequence-specific interactions with the DNA. These interactions are best portrayed as a landscape of TF binding affinities. Current methods to study sequence-specific binding preferences suffer from limited dynamic range, sequence bias, lack of specificity and limited throughput. We have developed a microfluidic-based device for SELEX Affinity Landscape MAPping (SELMAP) of TF binding, which allows high-throughput measurement of 16 proteins in parallel. We used it to measure the relative affinities of Pho4, AtERF2 and Btd full-length proteins to millions of different DNA binding sites, and detected both high and low-affinity interactions in equilibrium conditions, generating a comprehensive landscape of the relative TF affinities to all possible DNA 6-mers, and even DNA10-mers with increased sequencing depth. Low quantities of both the TFs and DNA oligomers were sufficient for obtaining high-quality results, significantly reducing experimental costs. SELMAP allows in-depth screening of hundreds of TFs, and provides a means for better understanding of the regulatory processes that govern gene expression. PMID:27628341

Perceived Intensity of Emotional Point-Light Displays Is Reduced in Subjects with ASD

ERIC Educational Resources Information Center

Krüger, Britta; Kaletsch, Morten; Pilgramm, Sebastian; Schwippert, Sven-Sören; Hennig, Jürgen; Stark, Rudolf; Lis, Stefanie; Gallhofer, Bernd; Sammer, Gebhard; Zentgraf, Karen; Munzert, Jörn

2018-01-01

One major characteristic of autism spectrum disorder (ASD) is problems with social interaction and communication. The present study explored ASD-related alterations in perceiving emotions expressed via body movements. 16 participants with ASD and 16 healthy controls observed video scenes of human interactions conveyed by point-light displays. They…

Interaction of the SPG21 protein ACP33/maspardin with the aldehyde dehydrogenase ALDH16A1

PubMed Central

2017-01-01

Mast syndrome (SPG21) is an autosomal-recessive complicated form of hereditary spastic paraplegia characterized by dementia, thin corpus callosum, white matter abnormalities, and cerebellar and extrapyramidal signs in addition to spastic paraparesis. A nucleotide insertion resulting in premature truncation of the SPG21 gene product acidic cluster protein 33 (ACP33)/maspardin underlies this disorder, likely causing loss of protein function. However, little is known about the function of maspardin. Here, we report that maspardin localizes prominently to cytoplasm as well as to membranes, possibly at trans-Golgi network/late endosomal compartments. Immunoprecipitation of maspardin with identification of coprecipitating proteins by mass spectrometry revealed the aldehyde dehydrogenase ALDH16A1 as an interacting protein. This interaction was confirmed using overexpressed proteins as well as by fusion protein pull down experiments, and these proteins colocalized in cells. Further studies of the function of ALDH16A1 and the role of the maspardin–ALDH16A1 interaction in neuronal cells may clarify the cellular pathogenesis of Mast syndrome. PMID:19184135

Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses.

PubMed

De Colibus, Luigi; Wang, Xiangxi; Tijsma, Aloys; Neyts, Johan; Spyrou, John A B; Ren, Jingshan; Grimes, Jonathan M; Puerstinger, Gerhard; Leyssen, Pieter; Fry, Elizabeth E; Rao, Zihe; Stuart, David I

2015-10-01

The replication of enterovirus 71 (EV71) and coxsackievirus A16 (CVA16), which are the major cause of hand, foot and mouth disease (HFMD) in children, can be inhibited by the capsid binder GPP3. Here, we present the crystal structure of CVA16 in complex with GPP3, which clarifies the role of the key residues involved in interactions with the inhibitor. Based on this model, in silico docking was performed to investigate the interactions with the two next-generation capsid binders NLD and ALD, which we show to be potent inhibitors of a panel of enteroviruses with potentially interesting pharmacological properties. A meta-analysis was performed using the available structural information to obtain a deeper insight into those structural features required for capsid binders to interact effectively and also those that confer broad-spectrum anti-enterovirus activity.

The interaction between cannabis use and the Val158Met polymorphism of the COMT gene in psychosis: A transdiagnostic meta – analysis

PubMed Central

Schäfer, Annika Theresia; Damen, Thomas; Uittenboogaard, Aniek; Krolinski, Pauline; Nwosu, Chinyere Vicky; Pinckaers, Florentina Maria Egidius; Rotee, Iris Leah Marije; Ermiş, Ayşegül; Kennedy, James L.; Nieman, Dorien H.; Tiwari, Arun; van Os, Jim

2018-01-01

Background Neither environmental nor genetic factors are sufficient to predict the transdiagnostic expression of psychosis. Therefore, analysis of gene-environment interactions may be productive. Objective A meta-analysis was performed using papers investigating the interaction between cannabis use and catechol-O-methyl transferase (COMT) polymorphism Val158Met (COMTVal158Met). Data sources PubMed, Embase, PsychInfo. Study eligibility criteria All observational studies assessing the interaction between COMTVal158Met and cannabis with any psychosis or psychotic symptoms measure as an outcome. Study appraisal and synthesis methods A meta-analysis was performed using the Meta-analysis of Observational Studies in Epidemiology guidelines and forest plots were generated. Thirteen articles met the selection criteria: 7 clinical studies using a case-only design, 3 clinical studies with a dichotomous outcome, and 3 studies analysing a continuous outcome of psychotic symptoms below the threshold of psychotic disorder. The three study types were analysed separately. Validity of the included studies was assessed using "A Cochrane Risk of Bias Assessment Tool: for Non-Randomized Studies of Interventions". Results For case-only studies, a significant interaction was found between cannabis use and COMTVal158Met, with an OR of 1.45 (95% Confidence Interval = 1.05–2.00; Met/Met as the risk genotype). However, there was no evidence for interaction in either the studies including dichotomous outcomes (B = -0.51, 95% Confidence Interval -1.72, 0.70) or the studies including continuous outcomes (B = -0.04 95% Confidence Interval -0.16–0.08). Limitation A substantial part of the included studies used the case-only design, which has lower validity and tends to overestimate true effects. Conclusion The interaction term between cannabis use and COMTVal158Met was only statistically significant in the case-only studies, but not in studies using other clinical or non-clinical psychosis outcomes. Future additional high quality studies might change current perspectives, yet currently evidence for the interaction remains unconvincing. PMID:29444152

Simulation of Different Truncated p16INK4a Forms and In Silico Study of Interaction with Cdk4

PubMed Central

Fahham, Najmeh; Ghahremani, Mohammad Hossein; Sardari, Soroush; Vaziri, Behrouz; Ostad, Seyed Nasser

2008-01-01

Protein-protein interactions studies can greatly increase the amount of structural and functional information pertaining to biologically active molecules and processes. The information obtained from such studies can lead to design and application of new modification in order to obtain a desired bioactivity. Many application packages and servers performing docking, such as HEX, DOT, AUTODOCK, and ZDOCK are now available for predicting the lowest free energy state of a protein complex. In this study, we have focused on cyclin-dependent kinase 4 (Cdk4), a key molecule in the regulation of cell cycle progression at the G1-S phase restriction point and p16INK4a, a tumor suppressor which inhibits Cdk4 activity. Truncated structures were created to find the more critical regions of p16 for interaction. The tertiary structures were determined by ProSAL, GENO3D Web Server. We evaluated their interactions with Cdk4 using two docking systems, HEX 4.5 and DOT 1. Calculations were performed on a high-speed computer. Minimizations and visualizations were carried out by PdbViewer 3.7. Considering shape and shape/electrostatic total energy, structures containing ANK II, III and IV motifs that lack the N-terminal region of the full length p16 molecule showed the best fit complexes among the p16 truncated forms. The free energies were compatible with that of p16 full length original form, the full length. It seems that the N-terminal of the molecule is not crucial for the interaction since the truncated structure containing only this region did not show a good total energy. PMID:19352455

Folding model analyses of 12C-12C and 16O-16O elastic scattering using the density-dependent LOCV-averaged effective interaction

NASA Astrophysics Data System (ADS)

Rahmat, M.; Modarres, M.

2018-03-01

The averaged effective two-body interaction (AEI), which can be generated through the lowest order constrained variational (LOCV) method for symmetric nuclear matter (SNM) with the input [Reid68, Ann. Phys. 50, 411 (1968), 10.1016/0003-4916(68)90126-7] nucleon-nucleon potential, is used as the effective nucleon-nucleon potential in the folding model to describe the heavy-ion (HI) elastic scattering cross sections. The elastic scattering cross sections of 12C-12C and 16O-16O systems are calculated in the above framework. The results are compared with the corresponding calculations coming from the fitting procedures with the input finite range D D M 3 Y 1 -Reid potential and the available experimental data at different incident energies. It is shown that a reasonable description of the elastic 12C-12C and 16O-16O scattering data at the low and medium energies can be obtained by using the above LOCV AEI, without any need to define a parametrized density-dependent function in the effective nucleon-nucleon potential, which is formally considered in the typical D D M 3 Y 1 -Reid interactions.

The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction.

PubMed

Francis, Michael M; Evans, Susan P; Jensen, Michael; Madsen, David M; Mancuso, Joel; Norman, Kenneth R; Maricq, Andres Villu

2005-05-19

Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate nervous system, underlies nicotine addiction, and nicotinic receptor dysfunction leads to neurological disorders. The C. elegans neuromuscular junction (NMJ) shares many characteristics with neuronal synapses, including multiple classes of postsynaptic currents. Here, we identify two genes required for the major excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic AChR subunit homologous to the vertebrate alpha7 subunit, and cam-1, which encodes a Ror receptor tyrosine kinase. acr-16 mutants lack fast cholinergic current at the NMJ and exhibit synthetic behavioral deficits with other known AChR mutants. In cam-1 mutants, ACR-16 is mislocalized and ACR-16-dependent currents are disrupted. The postsynaptic deficit in cam-1 mutants is accompanied by alterations in the distribution of cholinergic vesicles and associated synaptic proteins. We hypothesize that CAM-1 contributes to the localization or stabilization of postsynaptic ACR-16 receptors and presynaptic release sites.

Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity.

PubMed

Scudieri, Paolo; Musante, Ilaria; Gianotti, Ambra; Moran, Oscar; Galietta, Luis J V

2016-12-08

TMEM16A and TMEM16B are plasma membrane proteins with Ca 2+ -dependent Cl - channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the "activating domain" to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca 2+ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate that the enhanced activity in chimeric channels is due to altered interaction between the carboxy-terminus and the first intracellular loop in the TMEM16A homo-dimer. Mimicking this perturbation with a small molecule could be the basis for a pharmacological stimulation of TMEM16A-dependent Cl - transport.

Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity

PubMed Central

Scudieri, Paolo; Musante, Ilaria; Gianotti, Ambra; Moran, Oscar; Galietta, Luis J. V.

2016-01-01

TMEM16A and TMEM16B are plasma membrane proteins with Ca2+-dependent Cl− channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the “activating domain” to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca2+ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate that the enhanced activity in chimeric channels is due to altered interaction between the carboxy-terminus and the first intracellular loop in the TMEM16A homo-dimer. Mimicking this perturbation with a small molecule could be the basis for a pharmacological stimulation of TMEM16A-dependent Cl− transport. PMID:27929144

Intermolecular Interactions in the TMEM16A Dimer Controlling Channel Activity

NASA Astrophysics Data System (ADS)

Scudieri, Paolo; Musante, Ilaria; Gianotti, Ambra; Moran, Oscar; Galietta, Luis J. V.

2016-12-01

TMEM16A and TMEM16B are plasma membrane proteins with Ca2+-dependent Cl- channel function. By replacing the carboxy-terminus of TMEM16A with the equivalent region of TMEM16B, we obtained channels with potentiation of channel activity. Progressive shortening of the chimeric region restricted the “activating domain” to a short sequence close to the last transmembrane domain and led to TMEM16A channels with high activity at very low intracellular Ca2+ concentrations. To elucidate the molecular mechanism underlying this effect, we carried out experiments based on double chimeras, Forster resonance energy transfer, and intermolecular cross-linking. We also modeled TMEM16A structure using the Nectria haematococca TMEM16 protein as template. Our results indicate that the enhanced activity in chimeric channels is due to altered interaction between the carboxy-terminus and the first intracellular loop in the TMEM16A homo-dimer. Mimicking this perturbation with a small molecule could be the basis for a pharmacological stimulation of TMEM16A-dependent Cl- transport.

Globalization of Healthcare

PubMed Central

2012-01-01

Globalization—the increasing transnational circulation of money, goods, people, ideas, and information worldwide—is generally recognized as one of the most powerful forces shaping our current and future history. How is it affecting healthcare, and in that context, what is the purpose and significance of Global Advances in Health and Medicine (GAHM), publisher of this journal? Our goal is not homogenization but rather to provide an opportunity for integration, convergence, and collaboration across cultures. By respecting and conserving the richness and diversity of each new medicine, we embrace globalization. Globalization is of course not new; it began in the Renaissance and particularly with the 15th- and 16th-century voyages of exploration by Columbus, Magellan, and others. Since the beginning of time, there have been interactions and exchanges among different peoples and cultures. However, the current magnitude of globalization is unprecedented and yet still expanding rapidly. PMID:24278809

Clients' and therapists' real relationship and session quality in brief therapy: an actor partner interdependence analysis.

PubMed

Markin, Rayna D; Kivlighan, Dennis M; Gelso, Charles J; Hummel, Ann M; Spiegel, Eric B

2014-09-01

This study used the Actor Partner Interdependence Model (APIM; Kenny & Cook, 1999) to examine the associations of client- and therapist-rated real relationship (RR) and session quality over time. Eighty-seven clients and their therapists (n = 25) completed RR and session quality measures after every session of brief therapy. Therapists' current session quality ratings were significantly related to all of the following: session number (b = .04), their session quality rating of the previous session (b = .24), their RR in the previous session (b = 1.091), their client's RR in the previous session (b = .17), and interactions between their own and their clients' RR and session number (b = -.16 and β = -.04, respectively). Clients' ratings of current session quality were significantly related to only their own RR in the previous session (b = .47). Implications for future research and practice are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

47 CFR 7.16 - Informal or formal complaints.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Informal or formal complaints. 7.16 Section 7.16 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.16 Informal or formal...

47 CFR 7.16 - Informal or formal complaints.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 1 2013-10-01 2013-10-01 false Informal or formal complaints. 7.16 Section 7.16 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.16 Informal or formal...

47 CFR 7.16 - Informal or formal complaints.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 1 2012-10-01 2012-10-01 false Informal or formal complaints. 7.16 Section 7.16 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.16 Informal or formal...

47 CFR 7.16 - Informal or formal complaints.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 1 2014-10-01 2014-10-01 false Informal or formal complaints. 7.16 Section 7.16 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.16 Informal or formal...

47 CFR 7.16 - Informal or formal complaints.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 1 2011-10-01 2011-10-01 false Informal or formal complaints. 7.16 Section 7.16 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL ACCESS TO VOICEMAIL AND INTERACTIVE MENU SERVICES AND EQUIPMENT BY PEOPLE WITH DISABILITIES Enforcement § 7.16 Informal or formal...

Comprehensive identification of proteins binding to RNA G-quadruplex motifs in the 5' UTR of tumor-associated mRNAs.

PubMed

Serikawa, Tatsuo; Spanos, Christos; von Hacht, Annekathrin; Budisa, Nediljko; Rappsilber, Juri; Kurreck, Jens

2018-01-01

G-quadruplex structures in the 5' UTR of mRNAs are widely considered to suppress translation without affecting transcription. The current study describes the comprehensive analysis of proteins binding to four different G-quadruplex motifs located in mRNAs of the cancer-related genes Bcl-2, NRAS, MMP16, and ARPC2. Following metabolic labeling (Stable Isotope Labeling with Amino acids in Cell culture, SILAC) of proteins in the human cell line HEK293, G-quadruplex binding proteins were enriched by pull-down assays and identified by LC-orbitrap mass spectrometry. We found different patterns of interactions for the G-quadruplex motifs under investigation. While the G-quadruplexes in the mRNAs of NRAS and MMP16 specifically interacted with a small number of proteins, the Bcl-2 and ARPC2 G-quadruplexes exhibited a broad range of proteinaceous interaction partners with 99 and 82 candidate proteins identified in at least two replicates, respectively. The use of a control composed of samples from all G-quadruplex-forming sequences and their mutated controls ensured that the identified proteins are specific for RNA G-quadruplex structures and are not general RNA-binding proteins. Independent validation experiments based on pull-down assays and Western blotting confirmed the MS data. Among the interaction partners were many proteins known to bind to RNA, including multiple heterogenous nuclear ribonucleoproteins (hnRNPs). Several of the candidate proteins are likely to reflect stalling of the ribosome by RNA G-quadruplex structures. Interestingly, additional proteins were identified that have not previously been described to interact with RNA. Gene ontology analysis of the candidate proteins revealed that many interaction partners are known to be tumor related. The majority of the identified RNA G-quadruplex interacting proteins are thought to be involved in post-transcriptional processes, particularly in splicing. These findings indicate that protein-G-quadruplex interactions are not only important for the fine-tuning of translation but are also relevant to the regulation of mRNA maturation and may play an important role in tumor biology. Proteomic data are available via ProteomeXchange with identifier PXD005761. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Case Series Analysis of New Zealand Reports of Rapid Intense Potentiation of Warfarin by Roxithromycin.

PubMed

Savage, Ruth L; Tatley, Michael V

2018-05-01

We undertook an analysis of all the reports to the New Zealand Centre for Adverse Reactions Monitoring of a roxithromycin/warfarin interaction after two recent reports described intense rapid warfarin potentiation. The interaction was first published in 1995. Cytochrome P450 3A4 inhibition has been the proposed mechanism but has limited biologic plausibility. There are suggestions that the clinical significance of the interaction may be increased by severe illness, polypharmacy, renal dysfunction, older age and increased warfarin sensitivity. To investigate the potentiating effect of warfarin on roxithromycin in this New Zealand case series, the reports were reviewed to identify patients at risk, compare the reporting pattern with published Australian data and evaluate the appropriateness of current prescribing advice. Thirty patient reports were identified. The age range was 23-88 years, mean 66.8, median 73.0 (standard deviation 17.7) and the international normalised ratios after roxithromycin commencement ranged from 3.6 to 16.7 (mean 7.6, median 7.6, standard deviation 3.6). For eight patients with measurements on day 3, international normalised ratios were 4.3-16.7 (mean 10.4, median 8.8, standard deviation 4.4). Four patients had serious haemorrhage. Indications for roxithromycin were a range of respiratory tract infections. Anticoagulation was stable for most patients prior to acute infection. Serious infection occurred in 54.5% (12 of 22 patients with information). Polypharmacy (five or more medicines daily) was used by 36.7% of patients long term, increasing acutely to 83.3%, including additional potentially interacting medicines. Warfarin daily dose (1.5-13.0 mg, mean 4.4, median 4.0, standard deviation 2.2) was moderate to low. Pre-roxithromycin international normalised ratio values ranged from 1.4 to 3.7, mean and median 2.5, standard deviation 0.5. A high proportion of interactions were observed between warfarin and roxithromycin compared with other macrolides and compared with cytochrome P450 3A4-related macrolide interactions. The pattern was similar to published Australian data. In this case series, the high prevalence of acute polypharmacy, including potentially interacting medicines, and serious infection suggests that they may have contributed to warfarin potentiation and increased the clinical significance of a roxithromycin/warfarin interaction.

Parent-Child Interaction Processes Related to Scholastic Achievement in Urban Elementary Children.

ERIC Educational Resources Information Center

Portes, Pedro R.; And Others

In an attempt to identify parent-child interaction patterns that might differentiate bright from below-average elementary students, 16 high achievers and 16 low achievers were paired with their mothers and then videotaped whilst engaged in 3 sets of task situations, which involved copying of Block Design models and categorization of words and…

Genistein suppresses adhesion-induced protein tyrosine phosphorylation and invasion of B16-BL6 melanoma cells.

PubMed

Yan, C; Han, R

1998-07-03

Protein tyrosine phosphorylation occurs as one of the earlier events in cancer cell-extracellular matrix (ECM) interaction. With immunoblot analysis and immunofluorescence microscopy, genistein was found to suppress the tyrosine phosphorylation of proteins located at the cell periphery, including a 125 kDa protein, when B16-BL6 melanoma cells attached to and interacted with ECM. When accompanied by the suppression of adhesion-induced protein tyrosine phosphorylation, the invasive potential of B16-BL6 cells through reconstituted basement membrane was decreased significantly. However, neither adhesive capability nor cell growth was significantly affected by genistein. Therefore, the interruption of cancer cell-ECM interaction by suppression of protein tyrosine phosphorylation may contribute to invasion prevention of genistein.

Brivaracetam: An Adjunctive Treatment for Partial-Onset Seizures.

PubMed

Kappes, John A; Hayes, William J; Strain, Joe D; Farver, Debra K

2017-07-01

Brivaracetam is an analogue of levetiracetam that is Food and Drug Administration-approved for adjunctive treatment of partial-onset seizures in patients 16 years and older. In placebo-controlled trials adjunct brivaracetam demonstrated efficacy in reducing the frequency of seizures. The most commonly reported adverse effects are somnolence, dizziness, and fatigue. Clinical trials have evaluated brivaracetam for safety and efficacy in adjunctive treatment of partial-onset seizures in patients 16 years and older for up to 16 weeks. Brivaracetam's mechanism is similar to that of levetiracetam but with greater receptor binding affinity on synaptic vesicle protein 2A and inhibitory effects on sodium channels. Clinically significant differences between these agents are undetermined. Brivaracetam is available as oral tablets, oral solution, and intravenous solution. The Food and Drug Administration-approved dose is 50 mg twice daily, and titration is not required. Brivaracetam does not need dose adjustment for renal impairment and has minimal drug-drug interactions. Current limitations of brivaracetam include lack of head-to-head trials, limited long-term safety and efficacy data, and cost. Overall, brivaracetam is a viable adjunct therapeutic option for refractory partial-onset seizures in those who have failed conventional therapies. © 2017, The American College of Clinical Pharmacology.

Understanding the effects of MTV's 16 and Pregnant on adolescent girls' beliefs, attitudes, and behavioral intentions toward teen pregnancy.

PubMed

Aubrey, Jennifer Stevens; Behm-Morawitz, Elizabeth; Kim, Kyungbo

2014-01-01

This article examines the impact of a popular documentary series about teen pregnancy, MTV's 16 and Pregnant, on adolescent girls' pregnancy-related attitudes, beliefs, and behavioral intentions. The results suggest that girls who watched 16 and Pregnant, compared with a control group, reported a lower perception of their own risk for pregnancy and a greater perception that the benefits of teen pregnancy outweigh the risks. The authors also examined the relationships between homophily and parasocial interaction with the teen moms featured in 16 and Pregnant and attitudes, beliefs, and behavioral intentions, finding that homophily predicted lower risk perceptions, greater acceptance of myths about teen pregnancy, and more favorable attitudes about teen pregnancy. Parasocial interaction demonstrated the same pattern of results, with the addition of also predicting fewer behavioral intentions to avoid teen pregnancy. Last, results revealed that teen girls' perceptions that the message of 16 and Pregnant was encouraging of teen pregnancy predicted homophily and parasocial interaction with the teen moms. Theoretical and practical implications are discussed.

Visibiome: an efficient microbiome search engine based on a scalable, distributed architecture.

PubMed

Azman, Syafiq Kamarul; Anwar, Muhammad Zohaib; Henschel, Andreas

2017-07-24

Given the current influx of 16S rRNA profiles of microbiota samples, it is conceivable that large amounts of them eventually are available for search, comparison and contextualization with respect to novel samples. This process facilitates the identification of similar compositional features in microbiota elsewhere and therefore can help to understand driving factors for microbial community assembly. We present Visibiome, a microbiome search engine that can perform exhaustive, phylogeny based similarity search and contextualization of user-provided samples against a comprehensive dataset of 16S rRNA profiles environments, while tackling several computational challenges. In order to scale to high demands, we developed a distributed system that combines web framework technology, task queueing and scheduling, cloud computing and a dedicated database server. To further ensure speed and efficiency, we have deployed Nearest Neighbor search algorithms, capable of sublinear searches in high-dimensional metric spaces in combination with an optimized Earth Mover Distance based implementation of weighted UniFrac. The search also incorporates pairwise (adaptive) rarefaction and optionally, 16S rRNA copy number correction. The result of a query microbiome sample is the contextualization against a comprehensive database of microbiome samples from a diverse range of environments, visualized through a rich set of interactive figures and diagrams, including barchart-based compositional comparisons and ranking of the closest matches in the database. Visibiome is a convenient, scalable and efficient framework to search microbiomes against a comprehensive database of environmental samples. The search engine leverages a popular but computationally expensive, phylogeny based distance metric, while providing numerous advantages over the current state of the art tool.

Comparative modeling and docking studies of p16ink4/cyclin D1/Rb pathway genes in lung cancer revealed functionally interactive residue of RB1 and its functional partner E2F1.

PubMed

Naqsh e Zahra, Syeda; Khattak, Naureen Aslam; Mir, Asif

2013-01-01

Lung cancer is the major cause of mortality worldwide. Major signalling pathways that could play significant role in lung cancer therapy include (1) Growth promoting pathways (Epidermal Growth Factor Receptor/Ras/ PhosphatidylInositol 3-Kinase) (2) Growth inhibitory pathways (p53/Rb/P14ARF, STK11) (3) Apoptotic pathways (Bcl-2/Bax/Fas/FasL). Insilico strategy was implemented to solve the mystery behind selected lung cancer pathway by applying comparative modeling and molecular docking studies. YASARA [v 12.4.1] was utilized to predict structural models of P16-INK4 and RB1 genes using template 4ELJ-A and 1MX6-B respectively. WHAT CHECK evaluation tool demonstrated overall quality of predicted P16-INK4 and RB1 with Z-score of -0.132 and -0.007 respectively which showed a strong indication of reliable structure prediction. Protein-protein interactions were explored by utilizing STRING server, illustrated that CDK4 and E2F1 showed strong interaction with P16-INK4 and RB1 based on confidence score of 0.999 and 0.999 respectively. In order to facilitate a comprehensive understanding of the complex interactions between candidate genes with their functional interactors, GRAMM-X server was used. Protein-protein docking investigation of P16-INK4 revealed four ionic bonds illustrating Arg47, Arg80,Cys72 and Met1 residues as actively participating in interactions with CDK4 while docking results of RB1 showed four hydrogen bonds involving Glu864, Ser567, Asp36 and Arg861 residues which interact strongly with its respective functional interactor E2F1. This research may provide a basis for understanding biological insights of P16-INK4 and RB1 proteins which will be helpful in future to design a suitable drug to inhibit the disease pathogenesis as we have determined the interacting amino acids which can be targeted in order to design a ligand in-vitro to propose a drug for clinical trials. Protein -protein docking of candidate genes and their important interacting residues likely to be provide a gateway for developing computer aided drug designing.

Methyltransferase That Modifies Guanine 966 of the 16 S rRNA: FUNCTIONAL IDENTIFICATION AND TERTIARY STRUCTURE*

PubMed Central

Lesnyak, Dmitry V.; Osipiuk, Jerzy; Skarina, Tatiana; Sergiev, Petr V.; Bogdanov, Alexey A.; Edwards, Aled; Savchenko, Alexei; Joachimiak, Andrzej; Dontsova, Olga A.

2010-01-01

N2-Methylguanine 966 is located in the loop of Escherichia coli 16 S rRNA helix 31, forming a part of the P-site tRNA-binding pocket. We found yhhF to be a gene encoding for m2G966 specific 16 S rRNA methyltransferase. Disruption of the yhhF gene by kanamycin resistance marker leads to a loss of modification at G966. The modification could be rescued by expression of recombinant protein from the plasmid carrying the yhhF gene. Moreover, purified m2G966 methyltransferase, in the presence of S-adenosylomethionine (AdoMet), is able to methylate 30 S ribosomal subunits that were purified from yhhF knock-out strain in vitro. The methylation is specific for G966 base of the 16 S rRNA. The m2G966 methyltransferase was crystallized, and its structure has been determined and refined to 2.05 Å. The structure closely resembles RsmC rRNA methyltransferase, specific for m2G1207 of the 16 S rRNA. Structural comparisons and analysis of the enzyme active site suggest modes for binding AdoMet and rRNA to m2G966 methyltransferase. Based on the experimental data and current nomenclature the protein expressed from the yhhF gene was renamed to RsmD. A model for interaction of RsmD with ribosome has been proposed. PMID:17189261

Methyltransferase that modifies guanine 966 of the 16 S rRNA: functional identification and tertiary structure.

PubMed

Lesnyak, Dmitry V; Osipiuk, Jerzy; Skarina, Tatiana; Sergiev, Petr V; Bogdanov, Alexey A; Edwards, Aled; Savchenko, Alexei; Joachimiak, Andrzej; Dontsova, Olga A

2007-02-23

N(2)-Methylguanine 966 is located in the loop of Escherichia coli 16 S rRNA helix 31, forming a part of the P-site tRNA-binding pocket. We found yhhF to be a gene encoding for m(2)G966 specific 16 S rRNA methyltransferase. Disruption of the yhhF gene by kanamycin resistance marker leads to a loss of modification at G966. The modification could be rescued by expression of recombinant protein from the plasmid carrying the yhhF gene. Moreover, purified m(2)G966 methyltransferase, in the presence of S-adenosylomethionine (AdoMet), is able to methylate 30 S ribosomal subunits that were purified from yhhF knock-out strain in vitro. The methylation is specific for G966 base of the 16 S rRNA. The m(2)G966 methyltransferase was crystallized, and its structure has been determined and refined to 2.05A(.) The structure closely resembles RsmC rRNA methyltransferase, specific for m(2)G1207 of the 16 S rRNA. Structural comparisons and analysis of the enzyme active site suggest modes for binding AdoMet and rRNA to m(2)G966 methyltransferase. Based on the experimental data and current nomenclature the protein expressed from the yhhF gene was renamed to RsmD. A model for interaction of RsmD with ribosome has been proposed.

14 CFR 60.16 - Additional qualifications for a currently qualified FSTD.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Additional qualifications for a currently qualified FSTD. 60.16 Section 60.16 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE...

14 CFR 60.16 - Additional qualifications for a currently qualified FSTD.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Additional qualifications for a currently qualified FSTD. 60.16 Section 60.16 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE...

14 CFR 60.16 - Additional qualifications for a currently qualified FSTD.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Additional qualifications for a currently qualified FSTD. 60.16 Section 60.16 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE...

14 CFR 60.16 - Additional qualifications for a currently qualified FSTD.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Additional qualifications for a currently qualified FSTD. 60.16 Section 60.16 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRMEN FLIGHT SIMULATION TRAINING DEVICE INITIAL AND CONTINUING QUALIFICATION AND USE...

Anhydrosaccharides—A new class of the fragile plastic crystals

NASA Astrophysics Data System (ADS)

Kamińska, Ewa; Madejczyk, Olga; Tarnacka, Magdalena; Jurkiewicz, Karolina; Wolnica, Kamila; Śmiszek-Lindert, Wioleta Edyta; Kamiński, Kamil; Paluch, Marian

2018-02-01

In this paper, 1,6-anhydro-β-D-glucopyranose (anhGLU), 1,6-anhydro-β-D-mannopyranose (anhMAN), and 1,6-anhydro-β-D-galactopyranose (anhGAL), three new materials that form the Orientationally Disordered Crystal (ODIC) phase, have been thoroughly investigated using various experimental techniques. All measurements clearly indicated that these compounds possess a series of very interesting physical properties that are considerably different than those reported for ordinary plastic crystals. X-Ray diffraction investigations have revealed enormously long-range static correlations between molecules, reaching even 120 Å. Moreover, dielectric studies showed that besides Freon 113, the investigated anhydrosaccharides are the most fragile systems that form the ODIC phase. Further analysis of Fourier transform infrared spectra indicated that such peculiar behavior of anhydrosaccharides might be closely related to multidirectional H-bonds of various strengths that most likely affect the number of available conformations, density states, and the potential barriers in the energy landscape of these compounds. This is consistent with the results from previous reports [L. C. Pardo, J. Chem. Phys. 124, 124911 (2006) and Th. Bauer et al., J Chem. Phys. 133, 144509 (2010)] showing that the higher fragility of Freon 112 as well as a mixture of 60% succinonitrile and 40% glutaronitrile (60SN-40GN) can be closely related to the enhanced conformational ability and additional disorder introduced by various substituents, which further make energy landscape more complex. Finally, by studying the properties of 2,3,4-tri-O-acetyl-1,6-anhydro-β-D-glucopyranose (ac-anhGLU) it was found that besides the shape of the molecules, H-bonds or generally strong intermolecular interactions are extremely important parameters contributing to the ability to form the plastic phase. This is in line with current observations that in most cases the ODIC phase is created in highly interacting compounds.

Direct evidence for high affinity blockade of NaV1.6 channel subtype by huwentoxin-IV spider peptide, using multiscale functional approaches.

PubMed

Gonçalves, Tânia C; Boukaiba, Rachid; Molgó, Jordi; Amar, Muriel; Partiseti, Michel; Servent, Denis; Benoit, Evelyne

2018-05-01

The Chinese bird spider huwentoxin-IV (HwTx-IV) is well-known to be a highly potent blocker of Na V 1.7 subtype of voltage-gated sodium (Na V ) channels, a genetically validated analgesic target, and thus promising as a potential lead molecule for the development of novel pain therapeutics. In the present study, the interaction between HwTx-IV and Na V 1.6 channel subtype was investigated using multiscale (from in vivo to individual cell) functional approaches. HwTx-IV was approximatively 2 times more efficient than tetrodotoxin (TTX) to inhibit the compound muscle action potential recorded from the mouse skeletal neuromuscular system in vivo, and 30 times more effective to inhibit nerve-evoked than directly-elicited muscle contractile force of isolated mouse hemidiaphragms. These results strongly suggest that the inhibition of nerve-evoked skeletal muscle functioning, produced by HwTx-IV, resulted from a toxin-induced preferential blockade of Na V 1.6, compared to Na V 1.4, channel subtype. This was confirmed by whole-cell automated patch-clamp experiments performed on human embryonic kidney (HEK)-293 cells overexpressing hNa V 1.1-1.8 channel subtypes. HwTx-IV was also approximatively 850 times more efficient to inhibit TTX-sensitive than TTX-resistant sodium currents recorded from mouse dorsal root ganglia neurons. Finally, based on our data, we predict that blockade of the Na V 1.6 channel subtype was involved in the in vivo toxicity of HwTx-IV, although this toxicity was more than 2 times lower than that of TTX. In conclusion, our results provide detailed information regarding the effects of HwTx-IV and allow a better understanding of the side-effect mechanisms involved in vivo and of channel subtype interactions resulting from the toxin activity. Copyright © 2018 Elsevier Ltd. All rights reserved.

A Rendering System Independent High Level Architecture Implementation for Networked Virtual Environments

DTIC Science & Technology

2002-09-01

Management .........................15 5. Time Management ..............................16 6. Data Distribution Management .................16 D...50 b. Ownership Management .....................51 c. Data Distribution Management .............51 2. Additional Objects and Interactions...16 Figure 6. Data Distribution Management . (From: ref. 2) ...16 Figure 7. RTI and Federate Code Responsibilities. (From: ref. 2

Structural comparison of four different antibodies interacting with human papillomavirus 16 and mechanisms of neutralization

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

Guan, Jian; Bywaters, Stephanie M.; Brendle, Sarah A.

2015-09-15

Cryo-electron microscopy (cryo-EM) was used to solve the structures of human papillomavirus type 16 (HPV16) complexed with fragments of antibody (Fab) from three different neutralizing monoclonals (mAbs): H16.1A, H16.14J, and H263.A2. The structure-function analysis revealed predominantly monovalent binding of each Fab with capsid interactions that involved multiple loops from symmetry related copies of the major capsid protein. The residues identified in each Fab-virus interface map to a conformational groove on the surface of the capsomer. In addition to the known involvement of the FG and HI loops, the DE loop was also found to constitute the core of each epitope.more » Surprisingly, the epitope mapping also identified minor contributions by EF and BC loops. Complementary immunological assays included mAb and Fab neutralization. The specific binding characteristics of mAbs correlated with different neutralizing behaviors in pre- and post-attachment neutralization assays. - Highlights: • We present HPV16-Fab complexes from neutralizing mAbs: H16.1A, H16.14J, and H263.A2. • The structure-function analysis revealed predominantly monovalent binding of each mAb. • Capsid–Fab interactions involved multiple loops from symmetry related L1 proteins. • Besides the known FG and HI loops, epitope mapping also identified DE, EF, and BC loops. • Neutralizing assays complement the structures to show multiple neutralization mechanisms.« less

Evidence for ProTα-TLR4/MD-2 binding: molecular dynamics and gravimetric assay studies.

PubMed

Omotuyi, Olaposi; Matsunaga, Hayato; Ueda, Hiroshi

2015-01-01

During preconditioning, lipopolysaccharide (LPS) selectively activates TLR4/MD-2/Toll/IL-1 receptor-domain-containing adaptor inducing IFN-β (TRIF) pathway instead of pro-inflammatory myeloid differentiation protein-88 (MyD88)/MyD88-adaptor-like protein (MAL) pathway. Extracellular prothymosin alpha (ProTα) is also known to selectively activate the TLR4/MD2/TRIF-IRF3 pathway in certain diseased conditions. In the current study, biophysical evidence for ProTα/TLR4/MD-2 complex formation and its interaction dynamics have been studied. Gravimetric assay was used to investigate ProTα/TLR4/MD-2 complex formation while molecular dynamics (MD) simulation was used to study its interaction dynamics. Through electrostatic interaction, full-length ProTα (F-ProTα) C-terminal peptide (aa 91 - 111) superficially interacts with similar TLR4/MD-2 (KD = 273.36 nm vs 16.07 μg/ml [LPS]) conformation with LPS at an overlapping three-dimensional space while F-ProTα is hinged to the TLR4 scaffold by one-amino acid shift-Mosoian domain (aa-51 - 90). Comparatively, F-ProTα better stabilizes MD-2 metastable states transition and mediates higher TLR4/MD-2 interaction than LPS. ProTα via its C-terminal peptide (aa 91 - 111) exhibits in vitro biophysical contact with TLR4/MD-2 complex conformation recognized by LPS at overlapping LPS-binding positions.

The interaction between constituent year and within-1-year effects in elite German youth basketball.

PubMed

Steingröver, C; Wattie, N; Baker, J; Helsen, W F; Schorer, J

2017-06-01

The current state of research on relative age effects in basketball shows an uneven picture. These mixed results might be caused by the interaction of constituent year and within-year effects. Our aim was to examine constituent and within-1-year effects in elite German youth basketball. The sample (n = 4400) included players competing in the JBBL (Under-16 first division) and the NBBL (Under-19 first division) from 2011/2012 until 2013/2014. A multi-way frequency analysis revealed an interaction of constituent year effects and within-1-year effects for the JBBL, χ 2 (6, 2590) = 12.76, P < 0.05. NBBL data showed significant constituent year effects, χ 2 (2, n = 1810) = 25.32, P < 0.01, and within-1-year effects for all three age bands but no interaction. The interaction between constituent year and within-1-year effects in the JBBL showed reduced within-1-year effects with increasing age. Once players enter the system in the JBBL, relatively younger players seem less likely to drop out of the system. Results offer new insight regarding how the regulations of this talent development system may influence athletes' opportunities to enter the system and their likelihood of staying at the highest levels of competition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Final Report for "Tech-X Corporation work for the SciDAC Center for Simulation of RF Wave Interactions with Magnetohydrodynamics (SWIM)"

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

Jenkins, Thomas G.; Kruger, Scott E.

Work carried out by Tech-X Corporation for the DoE SciDAC Center for Simulation of RF Wave Interactions with Magnetohydrodynamics (SWIM; U.S. DoE Office of Science Award Number DE-FC02-06ER54899) is summarized and is shown to fulfil the project objectives. The Tech-X portion of the SWIM work focused on the development of analytic and computational approaches to study neoclassical tearing modes and their interaction with injected electron cyclotron current drive. Using formalism developed by Hegna, Callen, and Ramos [Phys. Plasmas 16, 112501 (2009); Phys. Plasmas 17, 082502 (2010); Phys. Plasmas 18, 102506 (2011)], analytic approximations for the RF interaction were derived andmore » the numerical methods needed to implement these interactions in the NIMROD extended MHD code were developed. Using the SWIM IPS framework, NIMROD has successfully coupled to GENRAY, an RF ray tracing code; additionally, a numerical control system to trigger the RF injection, adjustment, and shutdown in response to tearing mode activity has been developed. We discuss these accomplishments, as well as prospects for ongoing future research that this work has enabled (which continue in a limited fashion under the SciDAC Center for Extended Magnetohydrodynamic Modeling (CEMM) project and under a baseline theory grant). Associated conference presentations, published articles, and publications in progress are also listed.« less

The effect of external magnetic field on the bremsstrahlung nonlinear absorption mechanism in the interaction of high intensity short laser pulse with collisional underdense plasma

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

Sedaghat, M.; Ettehadi-Abari, M.; Shokri, B., E-mail: b-shokri@sbu.ac.ir

2015-03-15

Laser absorption in the interaction between ultra-intense femtosecond laser and solid density plasma is studied theoretically here in the intensity range Iλ{sup 2}≃10{sup 14}−10{sup 16}Wcm{sup −2}μm{sup 2}. The collisional effect is found to be significant when the incident laser intensity is less than 10{sup 16}Wcm{sup −2}μm{sup 2}. In the current work, the propagation of a high frequency electromagnetic wave, for underdense collisional plasma in the presence of an external magnetic field is investigated. It is shown that, by considering the effect of the ponderomotive force in collisional magnetized plasmas, the increase of laser pulse intensity leads to steepening of themore » electron density profile and the electron bunches of plasma makes narrower. Moreover, it is found that the wavelength of electric and magnetic fields oscillations increases by increasing the external magnetic field and the density distribution of electrons also grows in comparison with the unmagnetized collisional plasma. Furthermore, the spatial damping rate of laser energy and the nonlinear bremsstrahlung absorption coefficient are obtained in the collisional regime of magnetized plasma. The other remarkable result is that by increasing the external magnetic field in this case, the absorption coefficient increases strongly.« less

Fgf16 is essential for pectoral fin bud formation in zebrafish

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

Nomura, Ryohei; Kamei, Eriko; Hotta, Yuuhei

2006-08-18

Zebrafish pectoral fin bud formation is an excellent model for studying morphogenesis. Fibroblast growth factors (Fgfs) and sonic hedgehog (shh) are essential for pectoral fin bud formation. We found that Fgf16 was expressed in the apical ectodermal ridge (AER) of fin buds. A knockdown of Fgf16 function resulted in no fin bud outgrowth. Fgf16 is required for cell proliferation and differentiation in the mesenchyme and the AER of the fin buds, respectively. Fgf16 functions downstream of Fgf10, a mesenchymal factor, signaling to induce the expression of Fgf4 and Fgf8 in the AER. Fgf16 in the AER and shh in themore » zone of polarizing activity (ZPA) interact to induce and/or maintain each other's expression. These findings have revealed that Fgf16, a newly identified AER factor, plays a crucial role in pectoral fin bud outgrowth by mediating the interactions of AER-mesenchyme and AER-ZPA.« less

Calmodulin-dependent activation and inactivation of anoctamin calcium-gated chloride channels

PubMed Central

Vocke, Kerstin; Dauner, Kristin; Hahn, Anne; Ulbrich, Anne; Broecker, Jana; Keller, Sandro; Frings, Stephan

2013-01-01

Calcium-dependent chloride channels serve critical functions in diverse biological systems. Driven by cellular calcium signals, the channels codetermine excitatory processes and promote solute transport. The anoctamin (ANO) family of membrane proteins encodes three calcium-activated chloride channels, named ANO 1 (also TMEM16A), ANO 2 (also TMEM16B), and ANO 6 (also TMEM16F). Here we examined how ANO 1 and ANO 2 interact with Ca2+/calmodulin using nonstationary current analysis during channel activation. We identified a putative calmodulin-binding domain in the N-terminal region of the channel proteins that is involved in channel activation. Binding studies with peptides indicated that this domain, a regulatory calmodulin-binding motif (RCBM), provides two distinct modes of interaction with Ca2+/calmodulin, one at submicromolar Ca2+ concentrations and one in the micromolar Ca2+ range. Functional, structural, and pharmacological data support the concept that calmodulin serves as a calcium sensor that is stably associated with the RCBM domain and regulates the activation of ANO 1 and ANO 2 channels. Moreover, the predominant splice variant of ANO 2 in the brain exhibits Ca2+/calmodulin-dependent inactivation, a loss of channel activity within 30 s. This property may curtail ANO 2 activity during persistent Ca2+ signals in neurons. Mutagenesis data indicated that the RCBM domain is also involved in ANO 2 inactivation, and that inactivation is suppressed in the retinal ANO 2 splice variant. These results advance the understanding of Ca2+ regulation in anoctamin Cl− channels and its significance for the physiological function that anoctamin channels subserve in neurons and other cell types. PMID:24081981

The core microprocessor component DiGeorge syndrome critical region 8 (DGCR8) is a nonspecific RNA-binding protein.

PubMed

Roth, Braden M; Ishimaru, Daniella; Hennig, Mirko

2013-09-13

MicroRNA (miRNA) biogenesis follows a conserved succession of processing steps, beginning with the recognition and liberation of an miRNA-containing precursor miRNA hairpin from a large primary miRNA transcript (pri-miRNA) by the Microprocessor, which consists of the nuclear RNase III Drosha and the double-stranded RNA-binding domain protein DGCR8 (DiGeorge syndrome critical region protein 8). Current models suggest that specific recognition is driven by DGCR8 detection of single-stranded elements of the pri-miRNA stem-loop followed by Drosha recruitment and pri-miRNA cleavage. Because countless RNA transcripts feature single-stranded-dsRNA junctions and DGCR8 can bind hundreds of mRNAs, we explored correlations between RNA binding properties of DGCR8 and specific pri-miRNA substrate processing. We found that DGCR8 bound single-stranded, double-stranded, and random hairpin transcripts with similar affinity. Further investigation of DGCR8/pri-mir-16 interactions by NMR detected intermediate exchange regimes over a wide range of stoichiometric ratios. Diffusion analysis of DGCR8/pri-mir-16 interactions by pulsed field gradient NMR lent further support to dynamic complex formation involving free components in exchange with complexes of varying stoichiometry, although in vitro processing assays showed exclusive cleavage of pri-mir-16 variants bearing single-stranded flanking regions. Our results indicate that DGCR8 binds RNA nonspecifically. Therefore, a sequential model of DGCR8 recognition followed by Drosha recruitment is unlikely. Known RNA substrate requirements are broad and include 70-nucleotide hairpins with unpaired flanking regions. Thus, specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins.

The Core Microprocessor Component DiGeorge Syndrome Critical Region 8 (DGCR8) Is a Nonspecific RNA-binding Protein*

PubMed Central

Roth, Braden M.; Ishimaru, Daniella; Hennig, Mirko

2013-01-01

MicroRNA (miRNA) biogenesis follows a conserved succession of processing steps, beginning with the recognition and liberation of an miRNA-containing precursor miRNA hairpin from a large primary miRNA transcript (pri-miRNA) by the Microprocessor, which consists of the nuclear RNase III Drosha and the double-stranded RNA-binding domain protein DGCR8 (DiGeorge syndrome critical region protein 8). Current models suggest that specific recognition is driven by DGCR8 detection of single-stranded elements of the pri-miRNA stem-loop followed by Drosha recruitment and pri-miRNA cleavage. Because countless RNA transcripts feature single-stranded-dsRNA junctions and DGCR8 can bind hundreds of mRNAs, we explored correlations between RNA binding properties of DGCR8 and specific pri-miRNA substrate processing. We found that DGCR8 bound single-stranded, double-stranded, and random hairpin transcripts with similar affinity. Further investigation of DGCR8/pri-mir-16 interactions by NMR detected intermediate exchange regimes over a wide range of stoichiometric ratios. Diffusion analysis of DGCR8/pri-mir-16 interactions by pulsed field gradient NMR lent further support to dynamic complex formation involving free components in exchange with complexes of varying stoichiometry, although in vitro processing assays showed exclusive cleavage of pri-mir-16 variants bearing single-stranded flanking regions. Our results indicate that DGCR8 binds RNA nonspecifically. Therefore, a sequential model of DGCR8 recognition followed by Drosha recruitment is unlikely. Known RNA substrate requirements are broad and include 70-nucleotide hairpins with unpaired flanking regions. Thus, specific RNA processing is likely facilitated by preformed DGCR8-Drosha heterodimers that can discriminate between authentic substrates and other hairpins. PMID:23893406

The Human Papillomavirus E6 Oncogene Dysregulates the Cell Cycle and Contributes to Cervical Carcinogenesis through Two Independent Activities

PubMed Central

Shai, Anny; Brake, Tiffany; Somoza, Chamorro; Lambert, Paul F.

2010-01-01

Cervical cancer is a leading cause of death due to cancer among women worldwide. Using transgenic mice to dissect the contributions of the human papillomavirus (HPV) 16 E6 and E7 oncogenes in cervical cancer, E7 was identified previously to be the dominant oncogene. Specifically, when treated with exogenous estrogen for 6 months, E7 transgenic mice developed cancer throughout the reproductive tract, but E6 transgenic mice did not. E6 contributed to carcinogenesis of the reproductive tract, as E6/E7 double transgenic mice treated for 6 months with estrogen developed larger cancers than E7 transgenic mice. In the current study, we investigated whether the E6 oncogene alone could cooperate with estrogen to induce cervical cancer after an extended estrogen treatment period of 9 months. We found that the E6 oncogene synergizes with estrogen to induce cervical cancer after 9 months, indicating that E6 has a weaker but detectable oncogenic potential in the reproductive tract compared with the E7 oncogene. Using transgenic mice that express mutant forms of HPV16 E6, we determined that the interactions of E6 with cellular α-helix and PDZ partners correlate with its ability to induce cervical carcinogenesis. In analyzing the tumors arising in E6 transgenic mice, we learned that E6 induces expression of the E2F-responsive genes, Mcm7 and cyclin E, in the absence of the E7 oncogene. E6 also prevented the expression of p16 in tumors of the reproductive tract through a mechanism mediated by the interaction of E6 with α-helix partners. PMID:17308103

7 CFR 1962.16 - Accounting by County Supervisor.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 14 2010-01-01 2009-01-01 true Accounting by County Supervisor. 1962.16 Section 1962... § 1962.16 Accounting by County Supervisor. The Agency will maintain a current record of each borrower's... risk exists. An FO borrower who has been current with the Agency and who has provided chattels as...

Understanding college students' fruit consumption. Integrating habit strength in the theory of planned behaviour.

PubMed

de Bruijn, Gert-Jan

2010-02-01

The additive and interactive effect of habit strength in the explanation of young adults' fruit consumption was studied within the context of the theory of planned behaviour (TPB). Additionally, behavioural and control beliefs were modelled as predictors of profile membership based on current fruit consumption, motivation and habit strength towards fruit consumption. Cross-sectional data were available from undergraduate students (n=538; mean age=21.19; S.D.=2.57) who completed measures of fruit consumption, habit strength, TPB-concepts, and behavioural and control beliefs. Data were analyzed using stepwise regression analysis, simple slope analysis, and discriminant function analysis. Results showed that, based on a significant intention x habit interaction (beta=.13), the intention-fruit consumption relationship was more than twice as strong at low levels of habit strength (beta=.39) than at high levels of habit strength (beta=.16). Furthermore, beliefs regarding health and weight management were relatively unable to distinguish profiles created from motivation, habit strength and current fruit consumption. Rather, beliefs about controllability of fruit consumption were amongst the most consistent discriminating beliefs. Findings suggest that stronger fruit consumption habits make fruit consumption less intentional and that interventions aiming to increase fruit consumption may need to develop persuasive messages focusing on situational beliefs, rather than emphasizing health outcomes. 2009 Elsevier Ltd. All rights reserved.

CXCL16-positive dendritic cells enhance invariant natural killer T cell-dependent IFNγ production and tumor control

PubMed Central

Veinotte, Linnea; Gebremeskel, Simon; Johnston, Brent

2016-01-01

ABSTRACT Crosstalk interactions between dendritic cells (DCs) and invariant natural killer T (iNKT) cells are important in regulating antitumor responses elicited by glycolipid antigens. iNKT cells constitutively express the chemokine receptor CXCR6, while cytokine-activated DCs upregulate the transmembrane chemokine ligand, CXCL16. This study examined the co-stimulatory role of CXCR6/CXCL16 interactions in glycolipid-dependent iNKT cell activation and tumor control. Spleen and liver DCs in wild-type mice, but not iNKT cell deficient (Jα18−/−) mice, transiently upregulated surface CXCL16 following in vivo administration of the glycolipid antigen α-galactosylceramide. Recombinant CXCL16 did not directly induce iNKT cell activation in vitro but enhanced interferon (IFN)-γ production when mouse or human iNKT cells were stimulated with plate-bound anti-CD3. Compared with glycolipid-loaded CXCL16neg DCs, CXCL16hi DCs induced higher levels of IFNγ production in iNKT cell cultures and following adoptive transfer in vivo. The number of IFNγ+ iNKT cells and expansion of T-bet+ iNKT cells were reduced in vivo when CXCL16−/− DCs were used to activate iNKT cells. Enhanced IFNγ production in vivo was not dependent on CXCR6 expression on natural killer (NK) cells. Adoptive transfer of glycolipid-loaded CXCL16hi DCs provided superior protection against tumor metastasis compared to CXCL16neg DC transfers. Similarly, wild-type DCs provided superior protection against metastasis compared with CXCL16−/− DCs. These experiments implicate an important role for CXCR6/CXCL16 interactions in regulating iNKT cell IFNγ production and tumor control. The selective use of CXCL16hi DCs in adoptive transfer immunotherapies may prove useful for enhancing T helper (Th) type 1 responses and clinical outcomes in cancer patients. PMID:27471636

Inhibitory Effects of Honokiol on the Voltage-Gated Potassium Channels in Freshly Isolated Mouse Dorsal Root Ganglion Neurons.

PubMed

Sheng, Anqi; Zhang, Yan; Li, Guang; Zhang, Guangqin

2018-02-01

Voltage-gated potassium (K V ) currents, subdivided into rapidly inactivating A-type currents (I A ) and slowly inactivating delayed rectifier currents (I K ), play a fundamental role in modulating pain by controlling neuronal excitability. The effects of Honokiol (Hon), a natural biphenolic compound derived from Magnolia officinalis, on K V currents were investigated in freshly isolated mouse dorsal root ganglion neurons using the whole-cell patch clamp technique. Results showed that Hon inhibited I A and I K in concentration-dependent manner. The IC 50 values for block of I A and I K were 30.5 and 25.7 µM, respectively. Hon (30 µM) shifted the steady-state activation curves of I A and I K to positive potentials by 17.6 and 16.7 mV, whereas inactivation and recovery from the inactivated state of I A were unaffected. These results suggest that Hon preferentially interacts with the active states of the I A and I K channels, and has no effect on the resting state and inactivated state of the I A channel. Blockade on K + channels by Hon may contribute to its antinociceptive effect, especially anti-inflammatory pain.

Interactive optical panel

DOEpatents

Veligdan, James T.

1995-10-03

An interactive optical panel assembly 34 includes an optical panel 10 having a plurality of ribbon optical waveguides 12 stacked together with opposite ends thereof defining panel first and second faces 16, 18. A light source 20 provides an image beam 22 to the panel first face 16 for being channeled through the waveguides 12 and emitted from the panel second face 18 in the form of a viewable light image 24a. A remote device 38 produces a response beam 40 over a discrete selection area 36 of the panel second face 18 for being channeled through at least one of the waveguides 12 toward the panel first face 16. A light sensor 42,50 is disposed across a plurality of the waveguides 12 for detecting the response beam 40 therein for providing interactive capability.

Interaction of pepsin-[C16mim]Br system: interfacial dilational rheology and conformational studies.

PubMed

Huang, Tian; Cao, Chong; Liu, Zi-lin; Li, Yang; Du, Feng-pei

2014-09-21

The interfacial rheological property is closely related to the stabilities of foams and emulsions, yet there have been limited studies on the interaction between proteins with ionic liquid-type imidazolium surfactants at the decane-water interface as well as in the bulk. Herein, we investigated the interfacial and bulk properties of pepsin (PEP) and an ionic liquid (IL), 1-hexadecyl-3-methylimidazolium bromide, [C(16)mim]Br. The interfacial pressure and dilational rheology studies were performed to describe the formation of [C(16)mim]Br-pepsin complexes. The influence of the oscillating frequency and the bulk concentration of [C(16)mim]Br on the dilational properties were explored. The conformational changes were studied by monitoring the fluorescence and far UV-CD spectra. The results reveal that the globular structure of pepsin is one of the decisive factors controlling the nature of the interfacial film. The monotonous increase in the dilational elastic modulus of pepsin-[C(16)mim]Br solutions with the surface age indicates that no loops and tails had formed. Interestingly, with an increase in the concentration of [C(16)mim]Br, the εd-c curve first passes through a plateau value due to steric hindrance and the electrostatic barrier of already absorbed tenacious pepsin-[C(16)mim]Br complexes. With the further addition of [C(16)mim]Br, the remarkable decrease in dilational elastic modulus indicates that the compact structure is destroyed gradually. The results of the fluorescence spectra and far UV-CD spectra confirm that [C(16)mim]Br did not produce perceptible changes in pepsin at the concentrations studied in the dilational experiment. Possible schematic programs of the pepsin-[C(16)mim]Br interaction model at the interface and in bulk phase are proposed.

The A2Πi˜X2Σ+ interaction in CO +: Deperturbation analyses of B- A and A- X bands of 12C 16O +, 13C 16O + and 14C 16O +

NASA Astrophysics Data System (ADS)

Coxon, John A.; Kępa, Ryszard; Piotrowska, Izabela

2010-08-01

The 1-0, 6-0 and 6-1 bands of the A2Πi→X2Σ+ system of 13C 16O + and the 2-0 and 2-1 bands of the A2Πi→X2Σ+ system of 14C 16O + have been recorded at high resolution for the first time. The 0-2 and 5-0 bands of the A → X system of 12C 16O + have also been recorded at higher resolution than in previous work. The spectra were excited in an air-cooled hollow cathode discharge and photographed using a 2-m plane grating spectrograph. The spectral resolution and the Doppler-broadened line widths are both ˜0.12 cm -1, and the experimental measurement precision of resolved lines is ˜0.02 cm -1. The measured line positions, sometimes in combination with literature data on the B2Σ+→A2Πi transition, have been employed in deperturbation analyses of level crossings in the near-degenerate A(0)˜ X(10) and A(5)˜ X(14) interactions in 12C 16O +, the A(1)˜ X(11) and A(6)˜ X(15) interactions in 13C 16O +, and the A(2)˜ X(12) interaction in 14C 16O +. No radial dependence of the electronic perturbation matrix elements HSO( r) and HRE( r) could be detected over the narrow range of r-centroids (1.477-1.501 Å), and the mean values of these parameters are HSO = -49.06(15) cm -1 and HRE = 0.211(2). Using iteratively improved RKR potentials and FC-overlap integrals, the mean HSO and HRE were employed in least-squares analyses of A → X literature data involving A( υ) levels of the three isotopologues that are affected by interactions with one or two distant X( υ∗) levels. The fitted parameters of the A2Πi state ( B υ, A υ, A Dυ, p υ, q υ) exhibit υ-dependences that are much smoother than those employing perturbed parameters determined in previous investigations. In addition, a significant electronic isotope effect has been characterized. The separations Te( A)- Te( X) of the minima of the A and X states of 13C 16O + and 14C 16O + are less than that of 12C 16O + by 0.39 and 0.73 cm -1, respectively. Although Born-Oppenheimer breakdown of this magnitude is surprising, it is similar to that found for the B2Σ+ state of CO +.

Investigation of heavy-ion fusion with deformed surface diffuseness: Actinide and lanthanide targets

NASA Astrophysics Data System (ADS)

Alavi, S. A.; Dehghani, V.

2017-05-01

By using a deformed Broglia-Winther nuclear interaction potential in the framework of the WKB method, the near- and above-barrier heavy-ion-fusion cross sections of 16O with some lanthanides and actinides have been calculated. The effect of deformed surface diffuseness on the nuclear interaction potential, the effective interaction potential at distinct angle, barrier position, barrier height, cross section at each angles, and fusion cross sections of 16O+147Sm,150Nd,154Sm , and 166Er and 16O+232Th,238U,237Np , and 248Cm have been studied. The differences between the results obtained by using deformed surface diffuseness and those obtained by using constant surface diffuseness were noticeable. Good agreement between experimental data and theoretical calculation with deformed surface diffuseness were observed for 16O+147Sm,154Sm,166Er,238U,237Np , and 248Cm reactions. It has been observed that deformed surface diffuseness plays a significant role in heavy-ion-fusion studies.

Pulse electromagnetic fields enhance extracellular electron transfer in magnetic bioelectrochemical systems.

PubMed

Zhou, Huihui; Liu, Bingfeng; Wang, Qisong; Sun, Jianmin; Xie, Guojun; Ren, Nanqi; Ren, Zhiyong Jason; Xing, Defeng

2017-01-01

Microbial extracellular electron transfer (EET) is essential in driving the microbial interspecies interaction and redox reactions in bioelectrochemical systems (BESs). Magnetite (Fe 3 O 4 ) and magnetic fields (MFs) were recently reported to promote microbial EET, but the mechanisms of MFs stimulation of EET and current generation in BESs are not known. This study investigates the behavior of current generation and EET in a state-of-the-art pulse electromagnetic field (PEMF)-assisted magnetic BES (PEMF-MBES), which was equipped with magnetic carbon particle (Fe 3 O 4 @N-mC)-coated electrodes. Illumina Miseq sequencing of 16S rRNA gene amplicons was also conducted to reveal the changes of microbial communities and interactions on the anode in response to magnetic field. PEMF had significant influences on current generation. When reactors were operated in microbial fuel cell (MFC) mode with pulse electromagnetic field (PEMF-MMFCs), power densities increased by 25.3-36.0% compared with no PEMF control MFCs (PEMF-OFF-MMFCs). More interestingly, when PEMF was removed, the power density dropped by 25.7%, while when PEMF was reintroduced, the value was restored to the previous level. Illumina sequencing of 16S rRNA gene amplicon and principal component analysis (PCA) based on operational taxonomic units (OTUs) indicate that PEMFs led to the shifts in microbial community and changes in species evenness that decreased biofilm microbial diversity. Geobacter spp. were found dominant in all anode biofilms, but the relative abundance in PEMF-MMFCs (86.1-90.0%) was higher than in PEMF-OFF-MMFCs (82.5-82.7%), indicating that the magnetic field enriched Geobacter on the anode. The current generation of Geobacter -inoculated microbial electrolysis cells (MECs) presented the same change regularity, the accordingly increase or decrease corresponding with switch of PEMF, which confirmed the reversible stimulation of PEMFs on microbial electron transfer. The pulse electromagnetic field (PEMF) showed significant influence on state-of-the-art pulse magnetic bioelectrochemical systems (PEMF-MBES) in terms of current generation and microbial ecology. EET was instantaneously and reversibly enhanced in MBESs inoculated with either mixed-culture or Geobacter . PEMF notably decreased bacterial and archaeal diversities of the anode biofilms in MMFCs via changing species evenness rather than species richness, and facilitated specific enrichment of exoelectrogenic bacteria ( Geobacter ) on the anode surface. This study demonstrates a new magnetic approach for understanding and facilitating microbial electrochemical activities.

α-Dendrotoxin inhibits the ASIC current in dorsal root ganglion neurons from rat.

PubMed

Báez, Adriana; Salceda, Emilio; Fló, Martín; Graña, Martín; Fernández, Cecilia; Vega, Rosario; Soto, Enrique

2015-10-08

Dendrotoxins are a group of peptide toxins purified from the venom of several mamba snakes. α-Dendrotoxin (α-DTx, from the Eastern green mamba Dendroaspis angusticeps) is a well-known blocker of voltage-gated K(+) channels and specifically of K(v)1.1, K(v)1.2 and K(v)1.6. In this work we show that α-DTx inhibited the ASIC currents in DRG neurons (IC50=0.8 μM) when continuously perfused during 25 s (including a 5 s pulse to pH 6.1), but not when co-applied with the pH drop. Additionally, we show that α-DTx abolished a transient component of the outward current that, in some experiments, appeared immediately after the end of the acid pulse. Our data indicate that α-DTx inhibits ASICs in the high nM range while some Kv are inhibited in the low nM range. The α-DTx selectivity and its potential interaction with ASICs should be taken in consideration when DTx is used in the high nM range. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

FHF2 isoforms differentially regulate Nav1.6 mediated resurgent sodium currents in dorsal root ganglion neurons

PubMed Central

Barbosa, Cindy; Xiao, Yucheng; Johnson, Andrew J.; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming; Cummins, Theodore R.

2017-01-01

Nav1.6 and Nav1.6 mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6 mediated resurgent currents by isoforms of Fibroblast growth Factor Homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas, FHF2B enhances resurgent currents. Overall our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies. PMID:27999940

Highly Potent HIV-1 Protease Inhibitors with Novel Tricyclic P2-ligands: Design, Synthesis, and Protein-ligand X-Ray Studies

PubMed Central

Ghosh, Arun K.; Parham, Garth L.; Martyr, Cuthbert D.; Nyalapatla, Prasanth R.; Osswald, Heather L.; Agniswamy, Johnson; Wang, Yuan-Fang; Amano, Masayuki; Weber, Irene T.; Mitsuya, Hiroaki

2013-01-01

The design, synthesis, and biological evaluation of a series of HIV-1 protease inhibitors incorporating stereochemically defined fused tricyclic P2-ligands are described. Various substituent effects were investigated in order to maximize the ligand-binding site interactions in the protease active site. Inhibitors 16a and 16f showed excellent enzyme inhibitory and antiviral activity while incorporation of sulfone functionality resulted in a decrease in potency. Both inhibitors 16a and 16f have maintained activity against a panel of multidrug resistant HIV-1 variants. A high-resolution X-ray crystal structure of 16a-bound HIV-1 protease revealed important molecular insights into the ligand-binding site interactions which may account for the inhibitor’s potent antiviral activity and excellent resistance profiles. PMID:23947685

Laboratory simulation of the electrodynamic interactions of a tethered satellite with an ionospheric plasma

NASA Technical Reports Server (NTRS)

Bonifazi, C.; Lebreton, J. P.; Vannaroni, G.; Cosmovici, C.; Debrie, R.; Hamelin, M.; Pomathiod, L.; Arends, H.

1986-01-01

An improved experimental set-up in the Orleans Plasma Chamber allowed investigations of the I-V characteristics of a conductive spherical body (10 cm diameter) in a plasma environment. Moreover, the influence of a transversal magnetic field at 0.6 and 1.2 G was investigated, for the first time, both on the sheath potential profile and current collection. Floating potential profiles were measured at 16 different radial distances from the test body up to 9 body radii in 8 different angular positions. The test body potential could be increased in the range from -200 V up to +100 V. Preliminary results are shown and discussed.

A summary of the results from the UCLA OGO-5 fluxgate magnetometer

NASA Technical Reports Server (NTRS)

Coleman, P. J., Jr.; Russell, C. T.

1973-01-01

The OGO-5 fluxgate magnetometer experiment (E-14) was designed to measure the vector magnetic field over the full range of the OGO-5 orbit. Thus, it had a dynamic range of + or - 64,000 gamma yet it maintained a precision of + or - 1/16 gamma at all times. This enabled a broad spectrum of problems to be attached. Studies of the magnetospheric waves, currents, waves-particle interactions, pitch angle distributions and wave normal directions were made. The structure of the magnetopause, the magnetotail, and bow shock were probed, waves and discontinuities in the solar wind were examined and the various phases of substorms were examined in depth.

NMR diffusion and relaxation studies of 2-nitroimidazole and albumin interactions

NASA Astrophysics Data System (ADS)

Wijesekera, Dj; Willis, Scott A.; Gupta, Abhishek; Torres, Allan M.; Zheng, Gang; Price, William S.

2018-03-01

Nitroimidazole derivatives are of current interest in the development of hypoxia targeting agents and show potential in the establishment of quantitative measures of tumor hypoxia. In this study, the binding of 2-nitroimidazole to albumin was probed using NMR diffusion and relaxation measurements. Binding studies were conducted at three different protein concentrations (0.23, 0.30 and 0.38 mM) with drug concentrations ranging from 0.005-0.16 M at 298 K. Quantitative assessments of the binding model were made by evaluating the number of binding sites, n, and association constant, K. These were determined to be 21 ± 3 and 53 ± 4 M- 1, respectively.

Investigation of Sb-Containing Precursors for Cu(In, Ga)Se2 Thin Films Through Design of Experiments

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

Mansfield, Lorelle M.; To, Bobby; Reedy, Robert C.

2016-11-21

The Design of Experiments (DoE) module in JMP statistical software was used to determine the best parameters for Sb-containing CIGS precursors with a fixed selenization step. Solar cells were fabricated and measured for all completed films. The most important factor influencing the current-voltage device parameters was identified as the temperature and antimony flux interaction. The DoE prediction profiler and predictive contour plots provided guidance to further improve the device parameters. In one follow-up run, we increased device efficiency from 14.9% to 15.5% Additional gains in efficiency to 16.9% were realized by introducing an intentional Ga gradient and an antireflective coating.

Functional changes of the reward system underlie blunted response to social gaze in cocaine users

PubMed Central

Preller, Katrin H.; Herdener, Marcus; Schilbach, Leonhard; Stämpfli, Philipp; Hulka, Lea M.; Vonmoos, Matthias; Ingold, Nina; Vogeley, Kai; Tobler, Philippe N.; Seifritz, Erich; Quednow, Boris B.

2014-01-01

Social interaction deficits in drug users likely impede treatment, increase the burden of the affected families, and consequently contribute to the high costs for society associated with addiction. Despite its significance, the neural basis of altered social interaction in drug users is currently unknown. Therefore, we investigated basal social gaze behavior in cocaine users by applying behavioral, psychophysiological, and functional brain-imaging methods. In study I, 80 regular cocaine users and 63 healthy controls completed an interactive paradigm in which the participants’ gaze was recorded by an eye-tracking device that controlled the gaze of an anthropomorphic virtual character. Valence ratings of different eye-contact conditions revealed that cocaine users show diminished emotional engagement in social interaction, which was also supported by reduced pupil responses. Study II investigated the neural underpinnings of changes in social reward processing observed in study I. Sixteen cocaine users and 16 controls completed a similar interaction paradigm as used in study I while undergoing functional magnetic resonance imaging. In response to social interaction, cocaine users displayed decreased activation of the medial orbitofrontal cortex, a key region of reward processing. Moreover, blunted activation of the medial orbitofrontal cortex was significantly correlated with a decreased social network size, reflecting problems in real-life social behavior because of reduced social reward. In conclusion, basic social interaction deficits in cocaine users as observed here may arise from altered social reward processing. Consequently, these results point to the importance of reinstatement of social reward in the treatment of stimulant addiction. PMID:24449854

Measurement of inclusive radiative B-meson decay B decaying to X(S) meson-gamma

NASA Astrophysics Data System (ADS)

Ozcan, Veysi Erkcan

Radiative decays of the B meson, B→ Xsgamma, proceed via virtual flavor changing neutral current processes that are sensitive to contributions from high mass scales, either within the Standard Model of electroweak interactions or beyond. In the Standard Model, these transitions are sensitive to the weak interactions of the top quark, and relatively robust predictions of the inclusive decay rate exist. Significant deviation from these predictions could be interpreted as indications for processes not included in the minimal Standard Model, like interactions of charged Higgs or SUSY particles. The analysis of the inclusive photon spectrum from B→ Xsgamma decays is rather challenging due to high backgrounds from photons emitted in the decay of mesons in B decays as well as e+e- annihilation to low mass quark and lepton pairs. Based on 88.5 million BB events collected by the BABAR detector, the photon spectrum above 1.9 GeV is presented. By comparison of the first and second moments of the photon spectrum with QCD predictions (calculated in the kinetic scheme), QCD parameters describing the bound state of the b quark in the B meson are extracted: mb=4.45+/-0.16 GeV/c2m2 p=0.65+/-0.29 GeV2 These parameters are useful input to non-perturbative QCD corrections to the semileptonic B decay rate and the determination of the CKM parameter Vub. Based on these parameters and heavy quark expansion, the full branching fraction is obtained as: BRB→X sgEg >1.6GeV=4.050.32 stat+/-0.38syst +/-0.29model x10-4. This result is in good agreement with previous measurements, the statistical and systematic errors are comparable. It is also in good agreement with the theoretical Standard Model predictions, and thus within the present errors there is no indication of any interactions not accounted for in the Standard Model. This finding implies strong constraints on physics beyond the Standard Model.

Structural model of dodecameric heat-shock protein Hsp21: Flexible N-terminal arms interact with client proteins while C-terminal tails maintain the dodecamer and chaperone activity.

PubMed

Rutsdottir, Gudrun; Härmark, Johan; Weide, Yoran; Hebert, Hans; Rasmussen, Morten I; Wernersson, Sven; Respondek, Michal; Akke, Mikael; Højrup, Peter; Koeck, Philip J B; Söderberg, Christopher A G; Emanuelsson, Cecilia

2017-05-12

Small heat-shock proteins (sHsps) prevent aggregation of thermosensitive client proteins in a first line of defense against cellular stress. The mechanisms by which they perform this function have been hard to define due to limited structural information; currently, there is only one high-resolution structure of a plant sHsp published, that of the cytosolic Hsp16.9. We took interest in Hsp21, a chloroplast-localized sHsp crucial for plant stress resistance, which has even longer N-terminal arms than Hsp16.9, with a functionally important and conserved methionine-rich motif. To provide a framework for investigating structure-function relationships of Hsp21 and understanding these sequence variations, we developed a structural model of Hsp21 based on homology modeling, cryo-EM, cross-linking mass spectrometry, NMR, and small-angle X-ray scattering. Our data suggest a dodecameric arrangement of two trimer-of-dimer discs stabilized by the C-terminal tails, possibly through tail-to-tail interactions between the discs, mediated through extended I X V X I motifs. Our model further suggests that six N-terminal arms are located on the outside of the dodecamer, accessible for interaction with client proteins, and distinct from previous undefined or inwardly facing arms. To test the importance of the I X V X I motif, we created the point mutant V181A, which, as expected, disrupts the Hsp21 dodecamer and decreases chaperone activity. Finally, our data emphasize that sHsp chaperone efficiency depends on oligomerization and that client interactions can occur both with and without oligomer dissociation. These results provide a generalizable workflow to explore sHsps, expand our understanding of sHsp structural motifs, and provide a testable Hsp21 structure model to inform future investigations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Associations of smoking and alcohol consumption with impaired β-cell function in Chinese men.

PubMed

Xu, Min; Zhou, Yulin; Xu, Baihui; Sun, Jichao; Wang, Tiange; Lu, Jieli; Lai, Shenghan; Bi, Yufang; Wang, Weiqing; Ning, Guang

2016-05-01

The aims of the present study were to examine the association of cigarette smoking and alcohol consumption with impaired β-cell function in Chinese men, particularly the interaction of smoking and alcohol consumption on impaired insulin secretion. A population-based cross-sectional study was performed in 3957 Chinese men aged ≥40 years. The homeostatic model assessment of β-cell function (HOMA-β) was calculated, and impaired β-cell function was defined as less than the lowest quartile HOMA-βcut-off point. The prevalence of impaired β-cell function in current smokers and heavy drinkers (≥200 g/week) was significantly higher than in non-smokers and non-drinkers, respectively. Compared with non-smoking, current smoking had an exacerbating relationship with impaired β-cell function (odds ratio [OR] 1.78; 95% confidence interval [CI] 1.47-2.15; P < 0.001). No significant association was found between impaired β-cell function and former smoking (P = 0.21), although low and heavy drinking were associated with an increased risk of impaired β-cell function (OR 1.40 [95% CI 1.07-1.81] and 2.14 [95% CI 1.77-2.58], respectively) compared with non-drinking. The combination of current smoking and heavy drinking was associated with the highest risk of impaired β-cell function (OR 3.16; 95% CI 2.43-4.12; P < 0.0001) after adjustment for confounders. We did not detect an additive interaction between current smoking and heavy drinking on the association with impaired β-cell function. Cigarette smoking and alcohol consumption were significantly and independently associated with impaired β-cell function in Chinese men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Synthesis and characterization of amorphous mesoporous silica using TEMPO-functionalized amphiphilic templates

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

Vries, Wilke de; Doerenkamp, Carsten; Zeng, Zhaoyang

Inorganic–organic hybrid materials based on amorphous mesoporous silica containing organized nitroxide radicals within its mesopores have been prepared using the micellar self-assembly of TEOS solutions containing the nitroxide functionalized amphiphile (4-(N,N-dimethyl-N-hexadecylammonium)-2,2,6, 6-tetramethyl-piperidin-N-oxyl-iodide) (CAT-16). This template has been used both in its pure form and in various mixtures with cetyl trimethylammonium bromide (CTAB). The samples have been characterized by chemical analysis, N{sub 2} sorption studies, magnetic susceptibility measurements, and various spectroscopic methods. While electron paramagnetic resonance (EPR) spectra indicate that the strength of the intermolecular spin–spin interactions can be controlled via the CAT-16/CTAB ratio, nuclear magnetic resonance (NMR) data suggest thatmore » these interactions are too weak to facilitate cooperative magnetism. - Graphical abstract: The amphiphilic radical CAT-16 is used as a template for the synthesis of amorphous mesoporous silica. The resulting paramagnetic hybrid materials are characterized by BET, FTIR, NMR, EPR and magnetic susceptibility studies. - Highlights: • Amphiphilic CAT-16 as a template for mesoporous silica. • Comprehensive structural characterization by BET, FTIR; EPR and NMR. • Strength of radical-radical interactions tuable within CAT-16/CTAB mixtures.« less

Interactions between Natural Organic Matter and Native Microbes in the Oak Ridge FRC Groundwater

NASA Astrophysics Data System (ADS)

Wu, X.; Hazen, T.; Fox, P. M.; Nico, P. S.; Li, Q.; Yang, W.; Liu, Y.; Hess, N. J.; Zhang, P.; Qin, Y.; Zhou, J.; Chakraborty, R.

2016-12-01

Natural organic matter (NOM) is central to microbial food webs; however, little is known about the interplay between the physical and chemical characteristics of the carbon in NOM and its turnover by microbial communities. Microbial activity changes NOM's structure and properties, which may further influence the bioavailability of NOM. The change of NOM may reversely affect the microbial community structure as well. To date, our understanding of these interactions is insufficient, and it is critical to identify the role of NOM to carbon turnover, structure of microbial community and to the metabolic potential of that community. In this study, we aimed to study the interactions between NOM and native microbial communities present in groundwater at a background site (FW305 well) at Oak Ridge Field Research Center, TN. The total organic carbon and inorganic carbon in FW305 deep sediment samples were 0.071% and 0.011%, respectively. Water-soluble NOM was extracted from these sediment samples, the extraction efficiencies were 3.2% for organic carbon and 1.6% for inorganic carbon. The extracted NOM was then provided as the sole carbon source to native microbes present in groundwater. Subsamples were harvested several times from these incubations during a 50-day study. 16S rRNA gene amplicon sequencing and Geochip were used to identify the changes of microbial communities and expression of functional genes during transformation of the NOM. Several advanced chemical techniques including FTICR-MS and NEXAFS were used to characterize the C pool (i.e., NOM metabolites and microbial byproducts). Preliminary data clearly showed that microbial community responded to NOM, and shifted as functional groups in NOM transformed. Further detailed metabolite and gene-based analysis to elucidate these changes is currently being conducted.

Assessment of a gel-type chelating preparation containing 1-hydroxyethylidene-1, 1-bisphosphonate.

PubMed

Girard, S; Paqué, F; Badertscher, M; Sener, B; Zehnder, M

2005-11-01

To test an aqueous gel containing 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) regarding its interactions with sodium hypochlorite, its calcium binding capacity, and its potential in preventing the formation of a smear layer when used in conjunction with rotary root canal preparation. The experimental aqueous gel consisted of (w/v) 2% alginate, 3% aerosil, 10% Tween 80 and 18% HEBP. Interactions of gel components with hypochlorite were assessed using iodometric titration and monochromatic ultraviolet spectrometry. Two commercial paste-type chelators containing ethylenediaminetetraacetic acid (EDTA) and peroxide (RC-Prep and Glyde) served as controls. Calcium-binding capacities were measured in mixtures with a Ca2+ standard solution buffered at pH 10 using a calcium-selective measuring chain. Finally, root canals of 16 extracted single-rooted premolars per group were instrumented using ProFile instruments dipped in the experimental gel, RC-Prep, or nothing. Additionally, canals were rinsed with 10 mL of a 1% NaOCl solution during/after preparation. Smear scores in instrumented teeth were monitored using scanning electron microscopy. None of the experimental gel components showed short-term interactions with hypochlorite, whilst EDTA, peroxide, RC-Prep and Glyde immediately reduced the hypochlorite in solution. The experimental gel chelated 30 mg Ca2+ g-1, compared with 16 mg Ca2+ g-1 and 11 mg Ca2+ g-1 chelated by RC-Prep and Glyde respectively. Smear scores obtained with the experimental gel were significantly (P<0.05) lower than with RC-Prep in coronal and middle root thirds, whilst no differences were observed in apical root thirds. Under the conditions of this study, an HEBP gel appeared advantageous over currently available products.

DSMC Simulations of Hypersonic Flows With Shock Interactions and Validation With Experiments

NASA Technical Reports Server (NTRS)

Moss, James N.; Bird, Graeme A.

2004-01-01

The capabilities of a relatively new direct simulation Monte Carlo (DSMC) code are examined for the problem of hypersonic laminar shock/shock and shock/boundary layer interactions, where boundary layer separation is an important feature of the flow. Flow about two model configurations is considered, where both configurations (a biconic and a hollow cylinder-flare) have recent published experimental measurements. The computations are made by using the DS2V code of Bird, a general two-dimensional/axisymmetric time accurate code that incorporates many of the advances in DSMC over the past decade. The current focus is on flows produced in ground-based facilities at Mach 12 and 16 test conditions with nitrogen as the test gas and the test models at zero incidence. Results presented highlight the sensitivity of the calculations to grid resolutions, sensitivity to physical modeling parameters, and comparison with experimental measurements. Information is provided concerning the flow structure and surface results for the extent of separation, heating, pressure, and skin friction.

DSMC Simulations of Hypersonic Flows With Shock Interactions and Validation With Experiments

NASA Technical Reports Server (NTRS)

Moss, James N.; Bird, Graeme A.

2004-01-01

The capabilities of a relatively new direct simulation Monte Carlo (DSMC) code are examined for the problem of hypersonic laminar shock/shock and shock/boundary layer interactions, where boundary layer separation is an important feature of the flow. Flow about two model configurations is considered, where both configurations (a biconic and a hollow cylinder-flare) have recent published experimental measurements. The computations are made by using the DS2V code of Bird, a general two-dimensional/axisymmetric time accurate code that incorporates many of the advances in DSMC over the past decade. The current focus is on flows produced in ground-based facilities at Mach 12 and 16 test conditions with nitrogen as the test gas and the test models at zero incidence. Results presented highlight the sensitivity of the calculations to grid resolution, sensitivity to physical modeling parameters, and comparison with experimental measurements. Information is provided concerning the flow structure and surface results for the extent of separation, heating, pressure, and skin friction.

Stability analysis of a two-stage tapered gyrotron traveling-wave tube amplifier with distributed losses

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

Hung, C. L.; Lian, Y. H.; Cheng, N. H.

2012-11-15

The two-stage tapered gyrotron traveling-wave tube (gyro-TWT) amplifier has achieved wide bandwidth in the millimeter wave range. However, possible oscillations in each stage limit this amplifier's operating beam current and thus its output power. To further enhance the amplifier's stability, distributed losses are applied to the interaction circuit of the two-stage tapered gyro-TWT. A self-consistent particle-tracing code is used for analyzing the beam-wave interactions. The stability analysis includes the effects of the wall losses and the length of each stage on the possible oscillations. Simulation results reveal that the distributed-loss method effectively stabilizes all the oscillations in the two stages.more » Under stable operating conditions, the device is predicted to produce a peak power of 60 kW with an efficiency of 29% and a saturated gain of 52 dB in the Ka-band. The 3-dB bandwidth is 5.7 GHz, which is approximately 16% of the center frequency.« less

Region Evolution eXplorer - A tool for discovering evolution trends in ontology regions.

PubMed

Christen, Victor; Hartung, Michael; Groß, Anika

2015-01-01

A large number of life science ontologies has been developed to support different application scenarios such as gene annotation or functional analysis. The continuous accumulation of new insights and knowledge affects specific portions in ontologies and thus leads to their adaptation. Therefore, it is valuable to study which ontology parts have been extensively modified or remained unchanged. Users can monitor the evolution of an ontology to improve its further development or apply the knowledge in their applications. Here we present REX (Region Evolution eXplorer) a web-based system for exploring the evolution of ontology parts (regions). REX provides an analysis platform for currently about 1,000 versions of 16 well-known life science ontologies. Interactive workflows allow an explorative analysis of changing ontology regions and can be used to study evolution trends for long-term periods. REX is a web application providing an interactive and user-friendly interface to identify (un)stable regions in large life science ontologies. It is available at http://www.izbi.de/rex.

Magnetically leviated superconducting bearing

DOEpatents

Weinberger, Bernard R.; Lynds, Jr., Lahmer

1993-01-01

A magnetically levitated superconducting bearing includes a magnet (2) mounted on a shaft (12) that is rotatable around an axis of rotation and a Type II superconductor (6) supported on a stator (14) in proximity to the magnet (2). The superconductor (6) is positioned so that when it is cooled to its superconducting state in the presence of a magnetic field, it interacts with the magnet (2) to produce an attractive force that levitates the magnet (2) and supports a load on the shaft (12). The interaction between the superconductor (6) and magnet(2) also produces surface screening currents (8) that generate a repulsive force perpendicular to the load. The bearing also has means for maintaining the superconductor at a temperature below its critical temperature (16, 18). The bearing could also be constructed so the magnet (2) is supported on the stator (14) and the superconductor (6) is mounted on the shaft (12). The bearing can be operated by cooling the superconductor (6) to its superconducting state in the presence of a magnetic field.

Tumor suppressor C-RASSF proteins.

PubMed

Iwasa, Hiroaki; Hossain, Shakhawoat; Hata, Yutaka

2018-05-01

Human genome has ten genes that are collectedly called Ras association domain family (RASSF). RASSF is composed of two subclasses, C-RASSF and N-RASSF. Both N-RASSF and C-RASSF encode Ras association domain-containing proteins and are frequently suppressed by DNA hypermethylation in human cancers. However, C-RASSF and N-RASSF are quite different. Six C-RASSF proteins (RASSF1-6) are characterized by a C-terminal coiled-coil motif named Salvador/RASSF/Hippo domain, while four N-RASSF proteins (RASSF7-10) lack it. C-RASSF proteins interact with mammalian Ste20-like kinases-the core kinases of the tumor suppressor Hippo pathway-and cross-talk with this pathway. Some of them share the same interacting molecules such as MDM2 and exert the tumor suppressor role in similar manners. Nevertheless, each C-RASSF protein has distinct characters. In this review, we summarize our current knowledge of how C-RASSF proteins play tumor suppressor roles and discuss the similarities and differences among C-RASSF proteins.

A multidisciplinary study using in vivo tumor models and microfluidic cell-on-chip approach to explore the cross-talk between cancer and immune cells.

PubMed

Mattei, Fabrizio; Schiavoni, Giovanna; De Ninno, Adele; Lucarini, Valeria; Sestili, Paola; Sistigu, Antonella; Fragale, Alessandra; Sanchez, Massimo; Spada, Massimo; Gerardino, Annamaria; Belardelli, Filippo; Businaro, Luca; Gabriele, Lucia

2014-10-01

A full elucidation of events occurring inside the cancer microenvironment is fundamental for the optimization of more effective therapies. In the present study, the cross-talk between cancer and immune cells was examined by employing mice deficient (KO) in interferon regulatory factor (IRF)-8, a transcription factor essential for induction of competent immune responses. The in vivo results showed that IRF-8 KO mice were highly permissive to B16.F10 melanoma growth and metastasis due to failure of their immune cells to exert proper immunosurveillance. These events were found to be dependent on soluble factors released by cells of the immune system capable of shaping the malignant phenotype of melanoma cells. An on-chip model was then generated to further explore the reciprocal interactions between the B16.F10 and immune cells. B16.F10 and immune cells were co-cultured in a microfluidic device composed of three culturing chambers suitably inter-connected by an array of microchannels; mutual interactions were then followed using time-lapse microscopy. It was observed that WT immune cells migrated through the microchannels towards the B16.F10 cells, establishing tight interactions that in turn limited tumor spread. In contrast, IRF-8 KO immune cells poorly interacted with the melanoma cells, resulting in a more invasive behavior of the B16.F10 cells. These results suggest that IRF-8 expression plays a key role in the cross-talk between melanoma and immune cells, and under-score the value of cell-on-chip approaches as useful in vitro tools to reconstruct complex in vivo microenvironments on a microscale level to explore cell interactions such as those occurring within a cancer immunoenvironment.

Specificity of interactions among the DNA-packaging machine components of T4-related bacteriophages.

PubMed

Gao, Song; Rao, Venigalla B

2011-02-04

Tailed bacteriophages use powerful molecular motors to package the viral genome into a preformed capsid. Packaging at a rate of up to ∼2000 bp/s and generating a power density twice that of an automobile engine, the phage T4 motor is the fastest and most powerful reported to date. Central to DNA packaging are dynamic interactions among the packaging components, capsid (gp23), portal (gp20), motor (gp17, large "terminase"), and regulator (gp16, small terminase), leading to precise orchestration of the packaging process, but the mechanisms are poorly understood. Here we analyzed the interactions between small and large terminases of T4-related phages. Our results show that the gp17 packaging ATPase is maximally stimulated by homologous, but not heterologous, gp16. Multiple interaction sites are identified in both gp16 and gp17. The specificity determinants in gp16 are clustered in the diverged N- and C-terminal domains (regions I-III). Swapping of diverged region(s), such as replacing C-terminal RB49 region III with that of T4, switched ATPase stimulation specificity. Two specificity regions, amino acids 37-52 and 290-315, are identified in or near the gp17-ATPase "transmission" subdomain II. gp16 binding at these sites might cause a conformational change positioning the ATPase-coupling residues into the catalytic pocket, triggering ATP hydrolysis. These results lead to a model in which multiple weak interactions between motor and regulator allow dynamic assembly and disassembly of various packaging complexes, depending on the functional state of the packaging machine. This might be a general mechanism for regulation of the phage packaging machine and other complex molecular machines.

Human trophoblasts recruited T lymphocytes and monocytes into decidua by secretion of chemokine CXCL16 and interaction with CXCR6 in the first-trimester pregnancy.

PubMed

Huang, Yu; Zhu, Xiao-Yong; Du, Mei-Rong; Li, Da-Jin

2008-02-15

During human early pregnancy, fetus-derived trophoblasts come into direct contact with maternal immune cells at the maternofetal interface. At sites of placental attachment, invasive extravillous trophoblasts encounter decidual leukocytes (DLC) that accumulate within the decidua. Because we first found chemokine CXCL16 was highly expressed in and secreted by the first-trimester human trophoblasts previously, in this study we tested the hypothesis of whether the fetal trophoblasts can direct migration of maternal T lymphocyte and monocytes into decidua by secreting CXCL16. We analyzed the transcription and translation of CXCL16 in the isolated first-trimester human trophoblast, and examined the kinetic secretion of CXCL16 in the supernatant of the primary-cultured trophoblasts. We demonstrated that the sole receptor of CXCL16, CXCR6, is preferentially expressed in T lymphocytes, NKT cells, and monocytes, hardly expressed in two subsets of NK cells from either the peripheral blood or decidua. We further demonstrated the chemotactic activity of CXCL16 in the supernatant of the primary trophoblast on the peripheral mononuclear cells and DLC. Moreover, the CXCL16/CXCR6 interaction is involved in the migration of the peripheral T lymphocytes, gammadelta T cells, and monocytes, but not NKT cells. In addition, the trophoblast-conditioned medium could enrich PBMC subsets selectively to constitute a leukocyte population with similar composition to that of DLC, which suggests that the fetus-derived trophoblasts can attract T cells, gammadelta T cells, and monocytes by producing CXCL16 and interaction with CXCR6 on these cells, leading to forming a specialized immune milieu at the maternofetal interface.

Kr ion irradiation study of the depleted-uranium alloys

NASA Astrophysics Data System (ADS)

Gan, J.; Keiser, D. D.; Miller, B. D.; Kirk, M. A.; Rest, J.; Allen, T. R.; Wachs, D. M.

2010-12-01

Fuel development for the reduced enrichment research and test reactor (RERTR) program is tasked with the development of new low enrichment uranium nuclear fuels that can be employed to replace existing high enrichment uranium fuels currently used in some research reactors throughout the world. For dispersion type fuels, radiation stability of the fuel-cladding interaction product has a strong impact on fuel performance. Three depleted-uranium alloys are cast for the radiation stability studies of the fuel-cladding interaction product using Kr ion irradiation to investigate radiation damage from fission products. SEM analysis indicates the presence of the phases of interest: U(Al, Si) 3, (U, Mo)(Al, Si) 3, UMo 2Al 20, U 6Mo 4Al 43 and UAl 4. Irradiations of TEM disc samples were conducted with 500 keV Kr ions at 200 °C to ion doses up to 2.5 × 10 19 ions/m 2 (˜10 dpa) with an Kr ion flux of 10 16 ions/m 2/s (˜4.0 × 10 -3 dpa/s). Microstructural evolution of the phases relevant to fuel-cladding interaction products was investigated using transmission electron microscopy.

Intermittent fasting promotes prolonged associative interactions during synaptic tagging/capture by altering the metaplastic properties of the CA1 hippocampal neurons.

PubMed

Dasgupta, Ananya; Kim, Joonki; Manakkadan, Anoop; Arumugam, Thiruma V; Sajikumar, Sreedharan

2017-12-19

Metaplasticity is the inherent property of a neuron or neuronal population to undergo activity-dependent changes in neural function that modulate subsequent synaptic plasticity. Here we studied the effect of intermittent fasting (IF) in governing the interactions of associative plasticity mechanisms in the pyramidal neurons of rat hippocampal area CA1. Late long-term potentiation and its associative mechanisms such as synaptic tagging and capture at an interval of 120 min were evaluated in four groups of animals, AL (Ad libitum), IF12 (daily IF for 12 h), IF16 (daily IF for 16 h) and EOD (every other day IF for 24 h). IF had no visible effect on the early or late plasticity but it manifested a critical role in prolonging the associative interactions between weak and strong synapses at an interval of 120 min in IF16 and EOD animals. However, both IF12 and AL did not show associativity at 120 min. Plasticity genes such as Bdnf and Prkcz, which are well known for their expressions in late plasticity and synaptic tagging and capture, were significantly upregulated in IF16 and EOD in comparison to AL. Specific inhibition of brain derived neurotropic factor (BDNF) prevented the prolonged associativity expressed in EOD. Thus, daily IF for 16 h or more can be considered to enhance the metaplastic properties of synapses by improving their associative interactions that might translate into animprovedmemoryformation. Copyright © 2017. Published by Elsevier Inc.

A docking study of enhanced intracellular survival protein from Mycobacterium tuberculosis with human DUSP16/MKP-7.

PubMed

Yoon, Hye Jin; Kim, Kyoung Hoon; Yang, Jin Kuk; Suh, Se Won; Kim, Hyunsik; Jang, Soonmin

2013-11-01

The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis, and one of its secreted effector proteins, called enhanced intracellular survival (Eis) protein, enhances its survival in macrophages. Mtb Eis activates JNK-specific dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7) through the acetylation on Lys55, thus inactivating JNK by dephosphorylation. Based on the recently reported crystal structure of Mtb Eis, a docking model for the binding of Mtb Eis to DUSP16/MKP-7 was generated. In the docking model, the substrate helix containing Lys55 of DUSP16/MKP-7 fits nicely into the active-site cleft of Mtb Eis; the twisted β-sheet of Eis domain II embraces the substrate helix from one side. Most importantly, the side-chain of Lys55 is inserted toward acetyl-CoA and the resulting distance is 4.6 Å between the NZ atom of Lys55 and the carbonyl carbon of the acetyl group in acetyl-CoA. The binding of Mtb Eis and DUSP16/MKP-7 is maintained by strong electrostatic interactions. The active-site cleft of Mtb Eis has a negatively charged surface formed by Asp25, Glu138, Asp286, Glu395 and the terminal carboxylic group of Phe396. In contrast, DUSP16/MKP-7 contains five basic residues, Lys52, Lys55, Arg56, Arg57 and Lys62, which point toward the negatively charged surface of the active-site pocket of Mtb Eis. Thus, the current docking model suggests that the binding of DUSP16/MKP-7 to Mtb Eis should be established by charge complementarity in addition to a very favorable geometric arrangement. The suggested mode of binding requires the dissociation of the hexameric Mtb Eis into dimers or monomers. This study may be useful for future studies aiming to develop inhibitors of Mtb Eis as a new anti-tuberculosis drug candidate.

VHL negatively regulates SARS coronavirus replication by modulating nsp16 ubiquitination and stability.

PubMed

Yu, Xiao; Chen, Shuliang; Hou, Panpan; Wang, Min; Chen, Yu; Guo, Deyin

2015-04-03

Eukaryotic cellular and most viral RNAs carry a 5'-terminal cap structure, a 5'-5' triphosphate linkage between the 5' end of the RNA and a guanosine nucleotide (cap-0). SARS coronavirus (SARS-CoV) nonstructural protein nsp16 functions as a methyltransferase, to methylate mRNA cap-0 structure at the ribose 2'-O position of the first nucleotide to form cap-1 structures. However, whether there is interplay between nsp16 and host proteins was not yet clear. In this report, we identified several potential cellular nsp16-interacting proteins from a human thymus cDNA library by yeast two-hybrid screening. VHL, one of these proteins, was proven to interact with nsp16 both in vitro and in vivo. Further studies showed that VHL can inhibit SARS-CoV replication by regulating nsp16 ubiquitination and promoting its degradation. Our results have revealed the role of cellular VHL in the regulation of SARS-CoV replication. Copyright © 2015 Elsevier Inc. All rights reserved.

Event-based proactive interference in rhesus monkeys.

PubMed

Devkar, Deepna T; Wright, Anthony A

2016-10-01

Three rhesus monkeys (Macaca mulatta) were tested in a same/different memory task for proactive interference (PI) from prior trials. PI occurs when a previous sample stimulus appears as a test stimulus on a later trial, does not match the current sample stimulus, and the wrong response "same" is made. Trial-unique pictures (scenes, objects, animals, etc.) were used on most trials, except on trials where the test stimulus matched potentially interfering sample stimulus from a prior trial (1, 2, 4, 8, or 16 trials prior). Greater interference occurred when fewer trials separated interference and test. PI functions showed a continuum of interference. Delays between sample and test stimuli and intertrial intervals were manipulated to test how PI might vary as a function of elapsed time. Contrary to a similar study with pigeons, these time manipulations had no discernable effect on the monkey's PI, as shown by compete overlap of PI functions with no statistical differences or interactions. These results suggested that interference was strictly based upon the number of intervening events (trials with other pictures) without regard to elapsed time. The monkeys' apparent event-based interference was further supported by retesting with a novel set of 1,024 pictures. PI from novel pictures 1 or 2 trials prior was greater than from familiar pictures, a familiar set of 1,024 pictures. Moreover, when potentially interfering novel stimuli were 16 trials prior, performance accuracy was actually greater than accuracy on baseline trials (no interference), suggesting that remembering stimuli from 16 trials prior was a cue that this stimulus was not the sample stimulus on the current trial-a somewhat surprising conclusion particularly given monkeys.

COX16 promotes COX2 metallation and assembly during respiratory complex IV biogenesis

PubMed Central

Aich, Abhishek; Wang, Cong; Chowdhury, Arpita; Ronsör, Christin; Pacheu-Grau, David; Richter-Dennerlein, Ricarda; Dennerlein, Sven

2018-01-01

Cytochrome c oxidase of the mitochondrial oxidative phosphorylation system reduces molecular oxygen with redox equivalent-derived electrons. The conserved mitochondrial-encoded COX1- and COX2-subunits are the heme- and copper-center containing core subunits that catalyze water formation. COX1 and COX2 initially follow independent biogenesis pathways creating assembly modules with subunit-specific, chaperone-like assembly factors that assist in redox centers formation. Here, we find that COX16, a protein required for cytochrome c oxidase assembly, interacts specifically with newly synthesized COX2 and its copper center-forming metallochaperones SCO1, SCO2, and COA6. The recruitment of SCO1 to the COX2-module is COX16- dependent and patient-mimicking mutations in SCO1 affect interaction with COX16. These findings implicate COX16 in CuA-site formation. Surprisingly, COX16 is also found in COX1-containing assembly intermediates and COX2 recruitment to COX1. We conclude that COX16 participates in merging the COX1 and COX2 assembly lines. PMID:29381136

Deriving the nuclear shell model from first principles

NASA Astrophysics Data System (ADS)

Barrett, Bruce R.; Dikmen, Erdal; Vary, James P.; Maris, Pieter; Shirokov, Andrey M.; Lisetskiy, Alexander F.

2014-09-01

The results of an 18-nucleon No Core Shell Model calculation, performed in a large basis space using a bare, soft NN interaction, can be projected into the 0 ℏω space, i.e., the sd -shell. Because the 16 nucleons in the 16O core are frozen in the 0 ℏω space, all the correlations of the 18-nucleon system are captured by the two valence, sd -shell nucleons. By the projection, we obtain microscopically the sd -shell 2-body effective interactions, the core energy and the sd -shell s.p. energies. Thus, the input for standard shell-model calculations can be determined microscopically by this approach. If the same procedure is then applied to 19-nucleon systems, the sd -shell 3-body effective interactions can also be obtained, indicating the importance of these 3-body effective interactions relative to the 2-body effective interactions. Applications to A = 19 and heavier nuclei with different intrinsic NN interactions will be presented and discussed. The results of an 18-nucleon No Core Shell Model calculation, performed in a large basis space using a bare, soft NN interaction, can be projected into the 0 ℏω space, i.e., the sd -shell. Because the 16 nucleons in the 16O core are frozen in the 0 ℏω space, all the correlations of the 18-nucleon system are captured by the two valence, sd -shell nucleons. By the projection, we obtain microscopically the sd -shell 2-body effective interactions, the core energy and the sd -shell s.p. energies. Thus, the input for standard shell-model calculations can be determined microscopically by this approach. If the same procedure is then applied to 19-nucleon systems, the sd -shell 3-body effective interactions can also be obtained, indicating the importance of these 3-body effective interactions relative to the 2-body effective interactions. Applications to A = 19 and heavier nuclei with different intrinsic NN interactions will be presented and discussed. Supported by the US NSF under Grant No. 0854912, the US DOE under Grants Nos. DESC0008485 and DE-FG02-87ER40371, the Higher Education Council of Turkey(YOK), and the Ministry of Education and Science of Russian Fed. under contracts P521 and 14.v37.21.1297.

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2012 CFR

2012-01-01

... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2014 CFR

2014-01-01

... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

16 CFR Figures 1 and 2 to Part 1204 - Suggested Instrumentation for Current Monitoring Device and High Voltage Facility

Code of Federal Regulations, 2013 CFR

2013-01-01

... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Suggested Instrumentation for Current Monitoring Device and High Voltage Facility 1 Figures 1 and 2 to Part 1204 Commercial Practices CONSUMER... Instrumentation for Current Monitoring Device and High Voltage Facility EC03OC91.008 ...

Circumpolar assessment of rhizosphere priming shows limited increase in carbon loss estimates for permafrost soils but large regional variability

NASA Astrophysics Data System (ADS)

Wild, B.; Keuper, F.; Kummu, M.; Beer, C.; Blume-Werry, G.; Fontaine, S.; Gavazov, K.; Gentsch, N.; Guggenberger, G.; Hugelius, G.; Jalava, M.; Koven, C.; Krab, E. J.; Kuhry, P.; Monteux, S.; Richter, A.; Shazhad, T.; Dorrepaal, E.

2017-12-01

Predictions of soil organic carbon (SOC) losses in the northern circumpolar permafrost area converge around 15% (± 3% standard error) of the initial C pool by 2100 under the RCP 8.5 warming scenario. Yet, none of these estimates consider plant-soil interactions such as the rhizosphere priming effect (RPE). While laboratory experiments have shown that the input of plant-derived compounds can stimulate SOC losses by up to 1200%, the magnitude of RPE in natural ecosystems is unknown and no methods for upscaling exist so far. We here present the first spatial and depth explicit RPE model that allows estimates of RPE on a large scale (PrimeSCale). We combine available spatial data (SOC, C/N, GPP, ALT and ecosystem type) and new ecological insights to assess the importance of the RPE at the circumpolar scale. We use a positive saturating relationship between the RPE and belowground C allocation and two ALT-dependent rooting-depth distribution functions (for tundra and boreal forest) to proportionally assign belowground C allocation and RPE to individual soil depth increments. The model permits to take into account reasonable limiting factors on additional SOC losses by RPE including interactions between spatial and/or depth variation in GPP, plant root density, SOC stocks and ALT. We estimate potential RPE-induced SOC losses at 9.7 Pg C (5 - 95% CI: 1.5 - 23.2 Pg C) by 2100 (RCP 8.5). This corresponds to an increase of the current permafrost SOC-loss estimate from 15% of the initial C pool to about 16%. If we apply an additional molar C/N threshold of 20 to account for microbial C limitation as a requirement for the RPE, SOC losses by RPE are further reduced to 6.5 Pg C (5 - 95% CI: 1.0 - 16.8 Pg C) by 2100 (RCP 8.5). Although our results show that current estimates of permafrost soil C losses are robust without taking into account the RPE, our model also highlights high-RPE risk in Siberian lowland areas and Alaska north of the Brooks Range. The small overall impact of the RPE is largely explained by the interaction between belowground plant C allocation and SOC depth distribution. Our findings thus highlight the importance of fine scale interactions between plant and soil properties for large scale carbon fluxes and we provide a first model that bridges this gap and permits the quantification of RPE across a large area.

A Study on Wheel Sinkage and Rolling Resistance with variations in wheel geometry for Plain and Lugged wheels on TRI -1 Soil Simulant

NASA Astrophysics Data System (ADS)

Gireesh Kumar, Pala; Jayalekshmi, S.

2018-03-01

Wheel-soil Interaction studies are gaining momentum in the field of Terramechanics, but the basis is Terzaghi’s bearing capacity equation. For the current study, on a lunar soil simulant TRI – 1, two plain rigid wheels are considered, i.e., small wheel (dia. of 210 mm and width of 50 mm) and large wheel (dia. 160 mm and width 32 mm). Also, different number of lugs (N = 8, 12, 16) with various lug heights (h = 5 mm, 10 mm, 15 mm) are used. In this paper, the variation of wheel sinkages from experiments obtained for various wheel weights are examined and presented. The parameter, Coefficient of rolling resistance (CRR) is determined for various cases. Hence, rolling resistance was determined and examined from the obtained CRR for all cases. Among the cases examined, the large wheel with weight 67.44 N for plain wheels and weight 67.85 N for lugged wheel (no. of lugs = 16, and height of lugs = 5 mm) registered better mobility. Similarly, for small wheel with weight 52.189 N for plain wheel and weight 52.481 N for lugged wheel (no. of lugs = 16, and height of lugs = 5 mm) registered better mobility, a lesser rolling resistance for these cases.

Negative emotional reactivity as a marker of vulnerability in the development of borderline personality disorder symptoms

PubMed Central

Stepp, Stephanie D.; Scott, Lori N.; Jones, Neil P.; Whalen, Diana J.; Hipwell, Alison E.

2015-01-01

Negative emotionality is a distinguishing feature of borderline personality disorder (BPD). However, this person-level characteristic has not been examined as a marker of vulnerability in the development of this disorder. The current study utilized a multi-method approach to examine the interplay between negative emotional reactivity and cumulative exposure to family adversity on the development of BPD symptoms across three years (ages 16–18) in a diverse, at-risk sample of adolescent girls (N=113). A latent variable of negative emotional reactivity was created from multiple assessments at age 16: (1) self-report, (2) emotion ratings to stressors from ecological assessments across one week, and (3) observer-rated negative affectivity during a mother-daughter conflict discussion task. Exposure to family adversity was measured cumulatively between ages 5 and 16 from annual assessments of family poverty, single parent household, and difficult life circumstances. Results from latent growth curve models demonstrated a significant interaction between negative emotional reactivity and family adversity, such that exposure to adversity strengthened the association between negative emotional reactivity and BPD symptoms. Additionally, family adversity predicted increasing BPD symptoms during late adolescence. These findings highlight negative emotional reactivity as a marker of vulnerability that ultimately increases risk for the development of BPD symptoms. PMID:25925083

Negative emotional reactivity as a marker of vulnerability in the development of borderline personality disorder symptoms.

PubMed

Stepp, Stephanie D; Scott, Lori N; Jones, Neil P; Whalen, Diana J; Hipwell, Alison E

2016-02-01

Negative emotionality is a distinguishing feature of borderline personality disorder (BPD). However, this person-level characteristic has not been examined as a marker of vulnerability in the development of this disorder. The current study utilized a multimethod approach to examine the interplay between negative emotional reactivity and cumulative exposure to family adversity on the development of BPD symptoms across 3 years (ages 16-18) in a diverse, at-risk sample of adolescent girls (N = 113). A latent variable of negative emotional reactivity was created from multiple assessments at age 16: self-report, emotion ratings to stressors from ecological assessments across 1 week, and observer-rated negative affectivity during a mother-daughter conflict discussion task. Exposure to family adversity was measured cumulatively between ages 5 and 16 from annual assessments of family poverty, single parent household, and difficult life circumstances. The results from latent growth curve models demonstrated a significant interaction between negative emotional reactivity and family adversity, such that exposure to adversity strengthened the association between negative emotional reactivity and BPD symptoms. In addition, family adversity predicted increasing BPD symptoms during late adolescence. These findings highlight negative emotional reactivity as a marker of vulnerability that ultimately increases risk for the development of BPD symptoms.

The molecular mechanism of fullerene-inhibited aggregation of Alzheimer's β-amyloid peptide fragment

NASA Astrophysics Data System (ADS)

Xie, Luogang; Luo, Yin; Lin, Dongdong; Xi, Wenhui; Yang, Xinju; Wei, Guanghong

2014-07-01

Amyloid deposits are implicated in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease (AD). The inhibition of β-sheet formation has been considered as the primary therapeutic strategy for AD. Increasing data show that nanoparticles can retard or promote the fibrillation of amyloid-β (Aβ) peptides depending on the physicochemical properties of nanoparticles, however, the underlying molecular mechanism remains elusive. In this study, our replica exchange molecular dynamics (REMD) simulations show that fullerene nanoparticle - C60 (with a fullerene : peptide molar ratio greater than 1 : 8) can dramatically prevent β-sheet formation of Aβ(16-22) peptides. Atomic force microscopy (AFM) experiments further confirm the inhibitory effect of C60 on Aβ(16-22) fibrillation, in support of our REMD simulations. An important finding from our REMD simulations is that fullerene C180, albeit with the same number of carbon atoms as three C60 molecules (3C60) and smaller surface area than 3C60, displays an unexpected stronger inhibitory effect on the β-sheet formation of Aβ(16-22) peptides. A detailed analysis of the fullerene-peptide interaction reveals that the stronger inhibition of β-sheet formation by C180 results from the strong hydrophobic and aromatic-stacking interactions of the fullerene hexagonal rings with the Phe rings relative to the pentagonal rings. The strong interactions between the fullerene nanoparticles and Aβ(16-22) peptides significantly weaken the peptide-peptide interaction that is important for β-sheet formation, thus retarding Aβ(16-22) fibrillation. Overall, our studies reveal the significant role of fullerene hexagonal rings in the inhibition of Aβ(16-22) fibrillation and provide novel insight into the development of drug candidates against Alzheimer's disease.Amyloid deposits are implicated in the pathogenesis of many neurodegenerative diseases such as Alzheimer's disease (AD). The inhibition of β-sheet formation has been considered as the primary therapeutic strategy for AD. Increasing data show that nanoparticles can retard or promote the fibrillation of amyloid-β (Aβ) peptides depending on the physicochemical properties of nanoparticles, however, the underlying molecular mechanism remains elusive. In this study, our replica exchange molecular dynamics (REMD) simulations show that fullerene nanoparticle - C60 (with a fullerene : peptide molar ratio greater than 1 : 8) can dramatically prevent β-sheet formation of Aβ(16-22) peptides. Atomic force microscopy (AFM) experiments further confirm the inhibitory effect of C60 on Aβ(16-22) fibrillation, in support of our REMD simulations. An important finding from our REMD simulations is that fullerene C180, albeit with the same number of carbon atoms as three C60 molecules (3C60) and smaller surface area than 3C60, displays an unexpected stronger inhibitory effect on the β-sheet formation of Aβ(16-22) peptides. A detailed analysis of the fullerene-peptide interaction reveals that the stronger inhibition of β-sheet formation by C180 results from the strong hydrophobic and aromatic-stacking interactions of the fullerene hexagonal rings with the Phe rings relative to the pentagonal rings. The strong interactions between the fullerene nanoparticles and Aβ(16-22) peptides significantly weaken the peptide-peptide interaction that is important for β-sheet formation, thus retarding Aβ(16-22) fibrillation. Overall, our studies reveal the significant role of fullerene hexagonal rings in the inhibition of Aβ(16-22) fibrillation and provide novel insight into the development of drug candidates against Alzheimer's disease. Electronic supplementary information (ESI) available: The description of REMD simulations, analysis parameters, and AFM imaging of Aβ(16-22) aggregation with and without C60 nanoparticles, and three figures. The figures show the initial states, the convergence check for all the REMD runs, the PDF of the centroid distance (d) between the aromatic rings of Phe and its closest carbon ring, and the PDF of the angle between the two rings with a centroid distance of d <= 0.65 nm. See DOI: 10.1039/c4nr01005a

Drosophila Vps16A is required for trafficking to lysosomes and biogenesis of pigment granules.

PubMed

Pulipparacharuvil, Suprabha; Akbar, Mohammed Ali; Ray, Sanchali; Sevrioukov, Evgueny A; Haberman, Adam S; Rohrer, Jack; Krämer, Helmut

2005-08-15

Mutations that disrupt trafficking to lysosomes and lysosome-related organelles cause multiple diseases, including Hermansky-Pudlak syndrome. The Drosophila eye is a model system for analyzing such mutations. The eye-color genes carnation and deep orange encode two subunits of the Vps-C protein complex required for endosomal trafficking and pigment-granule biogenesis. Here we demonstrate that dVps16A (CG8454) encodes another Vps-C subunit. Biochemical experiments revealed a specific interaction between the dVps16A C-terminus and the Sec1/Munc18 homolog Carnation but not its closest homolog, dVps33B. Instead, dVps33B interacted with a related protein, dVps16B (CG18112). Deep orange bound both Vps16 homologs. Like a deep orange null mutation, eye-specific RNAi-induced knockdown of dVps16A inhibited lysosomal delivery of internalized ligands and interfered with biogenesis of pigment granules. Ubiquitous knockdown of dVps16A was lethal. Together, these findings demonstrate that Drosophila Vps16A is essential for lysosomal trafficking. Furthermore, metazoans have two types of Vps-C complexes with non-redundant functions.

Childhood measles contributes to post-bronchodilator airflow obstruction in middle-aged adults: A cohort study.

PubMed

Perret, Jennifer L; Matheson, Melanie C; Gurrin, Lyle C; Johns, David P; Burgess, John A; Thompson, Bruce R; Lowe, Adrian J; Markos, James; Morrison, Stephen S; McDonald, Christine F; Wood-Baker, Richard; Svanes, Cecilie; Thomas, Paul S; Hopper, John L; Giles, Graham G; Abramson, Michael J; Walters, E Haydn; Dharmage, Shyamali C

2018-03-20

Chronic obstructive pulmonary disease (COPD) has potential origins in childhood but an association between childhood measles and post-bronchodilator (BD) airflow obstruction (AO) has not yet been shown. We investigated whether childhood measles contributed to post-BD AO through interactions with asthma and/or smoking in a non-immunized middle-aged population. The population-based Tasmanian Longitudinal Health Study (TAHS) cohort born in 1961 (n = 8583) underwent spirometry in 1968 before immunization was introduced. A history of childhood measles infection was obtained from school medical records. During the fifth decade follow-up (n = 5729 responses), a subgroup underwent further lung function measurements (n = 1389). Relevant main associations and interactions by asthma and/or smoking on post-BD forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC; continuous variable) and AO (FEV 1 /FVC < lower limit of normal) were estimated by multiple regression. Sixty-nine percent (n = 950) had a history of childhood measles. Childhood measles augmented the combined adverse effect of current clinical asthma and smoking at least 10 pack-years on post-BD FEV 1 /FVC ratio in middle age (z-score: -0.70 (95% CI: -1.1 to -0.3) vs -1.36 (-1.6 to -1.1), three-way interaction: P = 0.009), especially for those with childhood-onset asthma. For never- and ever-smokers of <10 pack-years who had current asthma symptoms, compared with those without childhood measles, paradoxically, the odds for post-BD AO was not significant in the presence of childhood measles (OR: 12.0 (95% CI: 3.4-42) vs 2.17 (0.9-5.3)). Childhood measles infection appears to compound the associations between smoking, current asthma and post-BD AO. Differences between asthma subgroups provide further insight into the complex aetiology of obstructive lung diseases for middle-aged adults. © 2018 Asian Pacific Society of Respirology.

Momentum transfer in the reactions of 13. 6-GeV/nucleon sup 16 O with copper

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

Cumming, J.B.; Chu, Y.Y.; Haustein, P.E.

1992-11-01

Mean ranges and forward-to-backward ratios have been determined by the thick-target, thick-catcher technique for fragments from the interaction of 13.6-GeV/nucleon {sup 16}O with copper. Experimental data are analyzed in terms of a two-step model and results are discussed in the context of limiting fragmentation and factorization and the predictions of a simple model for momentum transfer. Momenta imparted in the initial interactions of 13.6-GeV/nucleon {sup 16}O were inferred to be {similar to}12% lower than those for fragmentation of Cu by high-energy protons.

PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity.

PubMed

Fruscione, Floriana; Valente, Pierluigi; Sterlini, Bruno; Romei, Alessandra; Baldassari, Simona; Fadda, Manuela; Prestigio, Cosimo; Giansante, Giorgia; Sartorelli, Jacopo; Rossi, Pia; Rubio, Alicia; Gambardella, Antonio; Nieus, Thierry; Broccoli, Vania; Fassio, Anna; Baldelli, Pietro; Corradi, Anna; Zara, Federico; Benfenati, Fabio

2018-04-01

See Lerche (doi:10.1093/brain/awy073) for a scientific commentary on this article.Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Single-cell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism.

PRRT2 controls neuronal excitability by negatively modulating Na+ channel 1.2/1.6 activity

PubMed Central

Fruscione, Floriana; Valente, Pierluigi; Sterlini, Bruno; Romei, Alessandra; Baldassari, Simona; Fadda, Manuela; Prestigio, Cosimo; Giansante, Giorgia; Sartorelli, Jacopo; Rossi, Pia; Rubio, Alicia; Gambardella, Antonio; Nieus, Thierry; Broccoli, Vania; Fassio, Anna; Baldelli, Pietro; Corradi, Anna; Zara, Federico

2018-01-01

Abstract See Lerche (doi:10.1093/brain/awy073) for a scientific commentary on this article. Proline-rich transmembrane protein 2 (PRRT2) is the causative gene for a heterogeneous group of familial paroxysmal neurological disorders that include seizures with onset in the first year of life (benign familial infantile seizures), paroxysmal kinesigenic dyskinesia or a combination of both. Most of the PRRT2 mutations are loss-of-function leading to haploinsufficiency and 80% of the patients carry the same frameshift mutation (c.649dupC; p.Arg217Profs*8), which leads to a premature stop codon. To model the disease and dissect the physiological role of PRRT2, we studied the phenotype of neurons differentiated from induced pluripotent stem cells from previously described heterozygous and homozygous siblings carrying the c.649dupC mutation. Single-cell patch-clamp experiments on induced pluripotent stem cell-derived neurons from homozygous patients showed increased Na+ currents that were fully rescued by expression of wild-type PRRT2. Closely similar electrophysiological features were observed in primary neurons obtained from the recently characterized PRRT2 knockout mouse. This phenotype was associated with an increased length of the axon initial segment and with markedly augmented spontaneous and evoked firing and bursting activities evaluated, at the network level, by multi-electrode array electrophysiology. Using HEK-293 cells stably expressing Nav channel subtypes, we demonstrated that the expression of PRRT2 decreases the membrane exposure and Na+ current of Nav1.2/Nav1.6, but not Nav1.1, channels. Moreover, PRRT2 directly interacted with Nav1.2/Nav1.6 channels and induced a negative shift in the voltage-dependence of inactivation and a slow-down in the recovery from inactivation. In addition, by co-immunoprecipitation assays, we showed that the PRRT2-Nav interaction also occurs in brain tissue. The study demonstrates that the lack of PRRT2 leads to a hyperactivity of voltage-dependent Na+ channels in homozygous PRRT2 knockout human and mouse neurons and that, in addition to the reported synaptic functions, PRRT2 is an important negative modulator of Nav1.2 and Nav1.6 channels. Given the predominant paroxysmal character of PRRT2-linked diseases, the disturbance in cellular excitability by lack of negative modulation of Na+ channels appears as the key pathogenetic mechanism. PMID:29554219

Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport

PubMed Central

Wulfmeyer, Vera Christine; Drewell, Hoora; Mutig, Kerim; Hou, Jianghui; Breiderhoff, Tilman; Müller, Dominik; Fromm, Michael; Bleich, Markus; Günzel, Dorothee

2017-01-01

The thick ascending limb (TAL) of Henle’s loop drives paracellular Na+, Ca2+, and Mg2+ reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing (trans) plasma membranes. The claudins Cldn10b, -16, and -19 facilitate cation reabsorption in the TAL, and their absence leads to a severe disturbance of renal ion homeostasis. We combined electrophysiological measurements on microperfused mouse TAL segments with subsequent analysis of claudin expression by immunostaining and confocal microscopy. Claudin interaction properties were examined using heterologous expression in the TJ-free cell line HEK 293, live-cell imaging, and Förster/FRET. To reveal determinants of interaction properties, a set of TAL claudin protein chimeras was created and analyzed. Our main findings are that (i) TAL TJs show a mosaic expression pattern of either cldn10b or cldn3/cldn16/cldn19 in a complex; (ii) TJs dominated by cldn10b prefer Na+ over Mg2+, whereas TJs dominated by cldn16 favor Mg2+ over Na+; (iii) cldn10b does not interact with other TAL claudins, whereas cldn3 and cldn16 can interact with cldn19 to form joint strands; and (iv) further claudin segments in addition to ECS2 are crucial for trans interaction. We suggest the existence of at least two spatially distinct types of paracellular channels in TAL: a cldn10b-based channel for monovalent cations such as Na+ and a spatially distinct site for reabsorption of divalent cations such as Ca2+ and Mg2+. PMID:28028216

Interaction between glycosaminoglycans and immunoglobulin light chains.

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

Jiang, X.; Myatt, E.; Lykos, P.

1997-01-01

Amyloidosis is a pathological process in which normally soluble proteins polymerize to form insoluble fibrils (amyloid). Amyloid formation is found in a number of diseases, including Alzheimer's disease, adult-onset diabetes, and light-chain-associated amyloidosis. No pharmaceutical methods currently exist to prevent this process or to remove the fibrils from tissue. The search for treatment and prevention methods is hampered by a limited understanding of the biophysical basis of amyloid formation. Glycosaminoglycans (GAGs) are long, unbranched heteropolysaccharides composed of repeating disaccharide subunits and are known to associate with amyloid fibrils. The interaction of amyloid-associated free light chains with GAGs was tested bymore » both size-exclusion high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis experiments. The results indicated that heparin 16 000 and chondroitin sulfate B and C precipitated both human intact light chains and recombinant light chain variable domains. Although all light chains interacted with heparin, the strongest interactions were obtained with proteins that had formed amyloid. Molecular modeling indicated the possibility of interaction between heparin and the conserved saddle like surface of the light chain dimer opposite the complementarity-determining segments that form part of the antigen-binding site of a functional antibody. This suggestion might offer a new path to block the aggregation of amyloid-associated light chain proteins, by design of antagonists based on properties of GAG binding. A hexasaccharide was modeled as the basis for a possible antagonist.« less

Aircraft modifications: Assessing the current state of Air Force aircraft modifications and the implications for future military capability

NASA Astrophysics Data System (ADS)

Hill, Owen Jacob

How prepared is the U.S. Air Force to modify its aircraft fleet in upcoming years? Aircraft modernization is a complex interaction of new and legacy aircraft, organizational structure, and planning policy. This research will take one component of modernization: aircraft modification, and apply a new method of analysis in order to help formulate policy to promote modernization. Departing from previous small-sample studies dependent upon weight as a chief explanatory variable, this dissertation incorporates a comprehensive dataset that was constructed for this research of all aircraft modifications from 1996 through 2005. With over 700 modification programs, this dataset is used to examine changes to the current modification policy using policy-response regression models. These changes include separating a codependent procurement and installation schedule, reducing the documentation requirements for safety modifications, and budgeting for aging aircraft modifications. The research then concludes with predictive models for the F-15 and F-16 along with their replacements: the F-22 and F-35 Joint Strike Fighter.

No tension between assembly models of super massive black hole binaries and pulsar observations.

PubMed

Middleton, Hannah; Chen, Siyuan; Del Pozzo, Walter; Sesana, Alberto; Vecchio, Alberto

2018-02-08

Pulsar timing arrays are presently the only means to search for the gravitational wave stochastic background from super massive black hole binary populations, considered to be within the grasp of current or near-future observations. The stringent upper limit from the Parkes Pulsar Timing Array has been interpreted as excluding (>90% confidence) the current paradigm of binary assembly through galaxy mergers and hardening via stellar interaction, suggesting evolution is accelerated or stalled. Using Bayesian hierarchical modelling we consider implications of this upper limit for a range of astrophysical scenarios, without invoking stalling, nor more exotic physical processes. All scenarios are fully consistent with the upper limit, but (weak) bounds on population parameters can be inferred. Recent upward revisions of the black hole-galaxy bulge mass relation are disfavoured at 1.6σ against lighter models. Once sensitivity improves by an order of magnitude, a non-detection will disfavour the most optimistic scenarios at 3.9σ.

Identification of chalcone-based antileishmanial agents targeting trypanothione reductase.

PubMed

Ortalli, Margherita; Ilari, Andrea; Colotti, Gianni; De Ionna, Ilenia; Battista, Theo; Bisi, Alessandra; Gobbi, Silvia; Rampa, Angela; Di Martino, Rita M C; Gentilomi, Giovanna A; Varani, Stefania; Belluti, Federica

2018-05-02

All currently used first-line and second-line drugs for the treatment of leishmaniasis exhibit several drawbacks including toxicity, high costs and route of administration. Furthermore, some drugs are associated with the emergence of drug resistance. Thus, the development of new treatments for leishmaniasis is a priority in the field of neglected tropical diseases. The present work highlights the use of natural derived products, i.e. chalcones, as potential source of antileishmanial agents. Thirty-one novel chalcone compounds have been synthesized and their activity has been evaluated against promastigotes of Leishmania donovani; 16 compounds resulted active against L. donovani in a range from 3.0 to 21.5 μM, showing low toxicity against mammalian cells. Among these molecules, 6 and 16 showed good inhibitory activity on both promastigotes and intracellular amastigotes, coupled with an high selectivity index. Furthermore, compounds 6 and 16 inhibited the promastigote growth of other leishmanial species, including L. tropica, L. major and L. infantum. Finally, 6 and 16 interacted with high affinity with trypanothione reductase (TR), an essential enzyme for the leishmanial parasite and compound 6 inhibited TR with sub-micromolar potency. Thus, the effective inhibitory activity against Leishmania, the lack of toxicity on mammalian cells and the ability to block a crucial parasite's enzyme, highlight the potential for compound 6 to be optimized as novel drug candidate against leishmaniasis. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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

Eberhard, Jeremy; Onder, Zeynep; Moroianu, Junona, E-mail: moroianu@bc.edu

We previously discovered that nuclear import of high risk HPV16 E7 is mediated by a cNLS located within the zinc-binding domain via a pathway that is independent of karyopherins/importins (Angeline et al., 2003; Knapp et al., 2009). In this study we continued our characterization of the cNLS and nuclear import pathway of HPV16 E7. We find that an intact zinc-binding domain is essential for the cNLS function in mediating nuclear import of HPV16 E7. Mutagenesis of cysteine residues to alanine in each of the two CysXXCys motifs involved in zinc-binding changes the nuclear localization of the EGFP-16E7 and 2xEGFP-16E7 mutants.more » We further discover that a patch of hydrophobic residues, {sub 65}LRLCV{sub 69}, within the zinc-binding domain of HPV16 E7 mediates its nuclear import via hydrophobic interactions with the FG domain of the central channel nucleoporin Nup62. - Highlights: • An intact zinc-binding domain is essential for the nuclear localization of HPV16 E7. • Identification of a hydrophobic patch that is critical for the nuclear import of HPV16 E7. • HPV16 E7 interacts via its zinc-binding domain with the FG domain of Nup62.« less

The impact of active and passive peer influence on young adult smoking: an experimental study.

PubMed

Harakeh, Zeena; Vollebergh, Wilma A M

2012-03-01

Peers influence adolescent and young adult smoking, but little is known about the underlying mechanisms. It is necessary to understand whether the current assumption of peer pressure is valid, or whether an alternative explanation as imitation is more appropriate. We examined whether passive (imitation) and/or active (pressure) peer influence affects young adult smoking. An experiment was conducted among 68 daily-smoking students aged 16-24. The actual study aim was masked. Participants had to do a 30-min music task with a confederate. The experiment consisted of a 2 (smoking condition: confederate smokes or not) by 2 (pressure condition: confederate offers the participant a cigarette or not) factorial design, resulting in four conditions: (1) no smoking and no pressure (N=15); (2) smoking but no pressure (N=16); (3) pressure but no smoking (N=20); and (4) smoking and pressure (N=17). The primary outcome tested was the total number of cigarettes smoked during this music assignment. Peer smoking significantly predicted the total number of cigarettes smoked by young adults while peer pressure did not. The interaction effect of peer pressure and peer smoking was not significant. Peer pressure did not have a significant additional contribution, over and above smoking of the peer. Passive (imitation) peer influence affected young adult smoking rather than active (pressure) peer influence. Thus, smoking cessation efforts should aim at preventing interaction with smoking peers and raising awareness about its impact. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Specific recognition of rpsO mRNA and 16S rRNA by Escherichia coli ribosomal protein S15 relies on both mimicry and site differentiation

PubMed Central

Mathy, Nathalie; Pellegrini, Olivier; Serganov, Alexander; Patel, Dinshaw J.; Ehresmann, Chantal; Portier, Claude

2015-01-01

Summary The ribosomal protein S15 binds to 16S rRNA, during ribosome assembly, and to its own mRNA (rpsO mRNA), affecting autocontrol of its expression. In both cases, the RNA binding site is bipartite with a common subsite consisting of a G•U/G-C motif. The second subsite is located in a three-way junction in 16S rRNA and in the distal part of a stem forming a pseudoknot in Escherichia coli rpsO mRNA. To determine the extent of mimicry between these two RNA targets, we determined which amino acids interact with rpsO mRNA. A plasmid carrying rpsO (the S15 gene) was mutagenized and introduced into a strain lacking S15 and harbouring an rpsO–lacZ translational fusion. Analysis of deregulated mutants shows that each subsite of rpsO mRNA is recognized by a set of amino acids known to interact with 16S rRNA. In addition to the G•U/G-C motif, which is recognized by the same amino acids in both targets, the other subsite interacts with amino acids also involved in contacts with helix H22 of 16S rRNA, in the region adjacent to the three-way junction. However, specific S15–rpsO mRNA interactions can also be found, probably with A(−46) in loop L1 of the pseudoknot, demonstrating that mimicry between the two targets is limited. PMID:15101974

Specific recognition of rpsO mRNA and 16S rRNA by Escherichia coli ribosomal protein S15 relies on both mimicry and site differentiation.

PubMed

Mathy, Nathalie; Pellegrini, Olivier; Serganov, Alexander; Patel, Dinshaw J; Ehresmann, Chantal; Portier, Claude

2004-05-01

The ribosomal protein S15 binds to 16S rRNA, during ribosome assembly, and to its own mRNA (rpsO mRNA), affecting autocontrol of its expression. In both cases, the RNA binding site is bipartite with a common subsite consisting of a G*U/G-C motif. The second subsite is located in a three-way junction in 16S rRNA and in the distal part of a stem forming a pseudoknot in Escherichia coli rpsO mRNA. To determine the extent of mimicry between these two RNA targets, we determined which amino acids interact with rpsO mRNA. A plasmid carrying rpsO (the S15 gene) was mutagenized and introduced into a strain lacking S15 and harbouring an rpsO-lacZ translational fusion. Analysis of deregulated mutants shows that each subsite of rpsO mRNA is recognized by a set of amino acids known to interact with 16S rRNA. In addition to the G*U/G-C motif, which is recognized by the same amino acids in both targets, the other subsite interacts with amino acids also involved in contacts with helix H22 of 16S rRNA, in the region adjacent to the three-way junction. However, specific S15-rpsO mRNA interactions can also be found, probably with A(-46) in loop L1 of the pseudoknot, demonstrating that mimicry between the two targets is limited.

Contribution of parenting to complex syntax development in preschool children with developmental delays or typical development.

PubMed

Moody, C T; Baker, B L; Blacher, J

2018-05-10

Despite studies of how parent-child interactions relate to early child language development, few have examined the continued contribution of parenting to more complex language skills through the preschool years. The current study explored how positive and negative parenting behaviours relate to growth in complex syntax learning from child age 3 to age 4 years, for children with typical development or developmental delays (DDs). Participants were children with or without DD (N = 60) participating in a longitudinal study of development. Parent-child interactions were transcribed and coded for parenting domains and child language. Multiple regression analyses were used to identify the contribution of parenting to complex syntax growth in children with typical development or DD. Analyses supported a final model, F(9,50) = 11.90, P < .001, including a significant three-way interaction between positive parenting behaviours, negative parenting behaviours and child delay status. This model explained 68.16% of the variance in children's complex syntax at age 4. Simple two-way interactions indicated differing effects of parenting variables for children with or without DD. Results have implications for understanding of complex syntax acquisition in young children, as well as implications for interventions. © 2018 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

Sex differences in cooperation: a meta-analytic review of social dilemmas.

PubMed

Balliet, Daniel; Li, Norman P; Macfarlan, Shane J; Van Vugt, Mark

2011-11-01

Although it is commonly believed that women are kinder and more cooperative than men, there is conflicting evidence for this assertion. Current theories of sex differences in social behavior suggest that it may be useful to examine in what situations men and women are likely to differ in cooperation. Here, we derive predictions from both sociocultural and evolutionary perspectives on context-specific sex differences in cooperation, and we conduct a unique meta-analytic study of 272 effect sizes-sampled across 50 years of research-on social dilemmas to examine several potential moderators. The overall average effect size is not statistically different from zero (d = -0.05), suggesting that men and women do not differ in their overall amounts of cooperation. However, the association between sex and cooperation is moderated by several key features of the social context: Male-male interactions are more cooperative than female-female interactions (d = 0.16), yet women cooperate more than men in mixed-sex interactions (d = -0.22). In repeated interactions, men are more cooperative than women. Women were more cooperative than men in larger groups and in more recent studies, but these differences disappeared after statistically controlling for several study characteristics. We discuss these results in the context of both sociocultural and evolutionary theories of sex differences, stress the need for an integrated biosocial approach, and outline directions for future research.

Reliability and efficacy of organic passivation for polycrystalline silicon solar cells at room temperature

NASA Astrophysics Data System (ADS)

Shinde, Onkar S.; Funde, Adinath M.; Jadkar, Sandesh R.; Dusane, Rajiv O.; Dhere, Neelkanth G.; Ghaisas, Subhash V.

2016-09-01

Oleylamine is used as a passivating layer instead of commercial high temperature SiNx. Oleylamine coating applied on the n-type emitter side with p-type base polycrystalline silicon solar cells at room temperature using a simple spin coating method. It has been observed that there is 16% increase in efficiency after Oleylamine coating. Further, the solar cell was subjected to standard characterization namely current-voltage measurement for electrical parameters and Fourier transform infrared spectroscopy to understand the interaction of emitter surface and passivating Oleylamine. However, the passivation layer is not stable due to the reaction between Oleylamine and ambient air content such as humidity and carbon dioxide. This degradation can be prevented with suitable overcoating.

Laser experiments to simulate coronal mass ejection driven magnetospheres and astrophysical plasma winds on compact magnetized stars

NASA Astrophysics Data System (ADS)

Horton, W.; Ditmire, T.; Zakharov, Yu. P.

2010-06-01

Laboratory experiments using a plasma wind generated by laser-target interaction are proposed to investigate the creation of a shock in front of the magnetosphere and the dynamo mechanism for creating plasma currents and voltages. Preliminary experiments are shown where measurements of the electron density gradients surrounding the obstacles are recorded to infer the plasma winds. The proposed experiments are relevant to understanding the electron acceleration mechanisms taking place in shock-driven magnetic dipole confined plasmas surrounding compact magnetized stars and planets. Exploratory experiments have been published [P. Brady, T. Ditmire, W. Horton, et al., Phys. Plasmas 16, 043112 (2009)] with the one Joule Yoga laser and centimeter sized permanent magnets.

Astrometrica: Astrometric data reduction of CCD images

NASA Astrophysics Data System (ADS)

Raab, Herbert

2012-03-01

Astrometrica is an interactive software tool for scientific grade astrometric data reduction of CCD images. The current version of the software is for the Windows 32bit operating system family. Astrometrica reads FITS (8, 16 and 32 bit integer files) and SBIG image files. The size of the images is limited only by available memory. It also offers automatic image calibration (Dark Frame and Flat Field correction), automatic reference star identification, automatic moving object detection and identification, and access to new-generation star catalogs (PPMXL, UCAC 3 and CMC-14), in addition to online help and other features. Astrometrica is shareware, available for use for a limited period of time (100 days) for free; special arrangements can be made for educational projects.

A new level of regulation in gluconeogenesis: metabolic state modulates the intracellular localization of aldolase B and its interaction with liver fructose-1,6-bisphosphatase.

PubMed

Droppelmann, Cristian A; Sáez, Doris E; Asenjo, Joel L; Yáñez, Alejandro J; García-Rocha, Mar; Concha, Ilona I; Grez, Manuel; Guinovart, Joan J; Slebe, Juan C

2015-12-01

Understanding how glucose metabolism is finely regulated at molecular and cellular levels in the liver is critical for knowing its relationship to related pathologies, such as diabetes. In order to gain insight into the regulation of glucose metabolism, we studied the liver-expressed isoforms aldolase B and fructose-1,6-bisphosphatase-1 (FBPase-1), key enzymes in gluconeogenesis, analysing their cellular localization in hepatocytes under different metabolic conditions and their protein-protein interaction in vitro and in vivo. We observed that glucose, insulin, glucagon and adrenaline differentially modulate the intracellular distribution of aldolase B and FBPase-1. Interestingly, the in vitro protein-protein interaction analysis between aldolase B and FBPase-1 showed a specific and regulable interaction between them, whereas aldolase A (muscle isozyme) and FBPase-1 showed no interaction. The affinity of the aldolase B and FBPase-1 complex was modulated by intermediate metabolites, but only in the presence of K(+). We observed a decreased association constant in the presence of adenosine monophosphate, fructose-2,6-bisphosphate, fructose-6-phosphate and inhibitory concentrations of fructose-1,6-bisphosphate. Conversely, the association constant of the complex increased in the presence of dihydroxyacetone phosphate (DHAP) and non-inhibitory concentrations of fructose-1,6-bisphosphate. Notably, in vivo FRET studies confirmed the interaction between aldolase B and FBPase-1. Also, the co-expression of aldolase B and FBPase-1 in cultured cells suggested that FBPase-1 guides the cellular localization of aldolase B. Our results provide further evidence that metabolic conditions modulate aldolase B and FBPase-1 activity at the cellular level through the regulation of their interaction, suggesting that their association confers a catalytic advantage for both enzymes. © 2015 Authors; published by Portland Press Limited.

Farfield Ion Current Density Measurements before and after the NASA HiVHAc EDU2 Vibration Test

NASA Technical Reports Server (NTRS)

Huang, Wensheng; Kamhawi, Hani; Shastry, Rohit

2012-01-01

There is an increasing need to characterize the plasma plume of the NASA HiVHAc thruster in order to better understand the plasma physics and to obtain data for spacecraft interaction studies. To address this need, the HiVHAc research team is in the process of developing a number of plume diagnostic systems. This paper presents the initial results of the farfield current density probe diagnostic system. Farfield current density measurements were carried out before and after a vibration test of the HiVHAc engineering development unit 2 that simulate typical launch conditions. The main purposes of the current density measurements were to evaluate the thruster plume divergence and to investigate any changes in the plasma plume that may occur as a result of the vibration test. Radial sweeps, as opposed to the traditional polar sweeps, were performed during these tests. The charged-weighted divergence angles were found to vary from 16 to 28 degrees. Charge density profiles measured pre- and post-vibration-test were found to be in excellent agreement. This result, alongside thrust measurements reported in a companion paper, confirm that the operation of the HiVHAc engineering development unit 2 were not altered by full-level/random vibration testing.

MOCCA: A 4k-Pixel Molecule Camera for the Position- and Energy-Resolving Detection of Neutral Molecule Fragments at CSR

NASA Astrophysics Data System (ADS)

Gamer, L.; Schulz, D.; Enss, C.; Fleischmann, A.; Gastaldo, L.; Kempf, S.; Krantz, C.; Novotný, O.; Schwalm, D.; Wolf, A.

2016-08-01

We present the design of MOCCA, a large-area particle detector that is developed for the position- and energy-resolving detection of neutral molecule fragments produced in electron-ion interactions at the Cryogenic Storage Ring at the Max Planck Institute for Nuclear Physics in Heidelberg. The detector is based on metallic magnetic calorimeters and consists of 4096 particle absorbers covering a total detection area of 44.8 mathrm {mm} × 44.8 mathrm {mm}. Groups of four absorbers are thermally coupled to a common paramagnetic temperature sensor where the strength of the thermal link is different for each absorber. This allows attributing a detector event within this group to the corresponding absorber by discriminating the signal rise times. A novel readout scheme further allows reading out all 1024 temperature sensors that are arranged in a 32 × 32 square array using only 16+16 current-sensing superconducting quantum interference devices. Numerical calculations taking into account a simplified detector model predict an energy resolution of Δ E_mathrm {FWHM} le 80 mathrm {eV} for all pixels of this detector.

The lung microbiome in health and disease.

PubMed

Moffatt, Miriam F; Cookson, William Ocm

2017-12-01

The Human Microbiome Project began 10 years ago, leading to a significant growth in understanding of the role the human microbiome plays in health and disease. In this article, we explain with an emphasis on the lung, the origins of microbiome research. We discuss how 16S rRNA gene sequencing became the first major molecular tool to examine the bacterial communities present within the human body. We highlight the pitfalls of molecular-based studies, such as false findings resulting from contamination, and the limitations of 16S rRNA gene sequencing. Knowledge about the lung microbiome has evolved from initial scepticism to the realisation that it might have a significant influence on many illnesses. We also discuss the lung microbiome in the context of disease by giving examples of important respiratory conditions. In addition, we draw attention to the challenges for metagenomic studies of respiratory samples and the importance of systematic bacterial isolation to enable host-microbiome interactions to be understood. We conclude by discussing how knowledge of the lung microbiome impacts current clinical diagnostics. © Royal College of Physicians 2017. All rights reserved.

Numerical and experimental study of a high port-density WDM optical packet switch architecture for data centers.

PubMed

Di Lucente, S; Luo, J; Centelles, R Pueyo; Rohit, A; Zou, S; Williams, K A; Dorren, H J S; Calabretta, N

2013-01-14

Data centers have to sustain the rapid growth of data traffic due to the increasing demand of bandwidth-hungry internet services. The current intra-data center fat tree topology causes communication bottlenecks in the server interaction process, power-hungry O-E-O conversions that limit the minimum latency and the power efficiency of these systems. In this paper we numerically and experimentally investigate an optical packet switch architecture with modular structure and highly distributed control that allow configuration times in the order of nanoseconds. Numerical results indicate that the candidate architecture scaled over 4000 ports, provides an overall throughput over 50 Tb/s and a packet loss rate below 10(-6) while assuring sub-microsecond latency. We present experimental results that demonstrate the feasibility of a 16x16 optical packet switch based on parallel 1x4 integrated optical cross-connect modules. Error-free operations can be achieved with 4 dB penalty while the overall energy consumption is of 66 pJ/b. Based on those results, we discuss feasibility to scale the architecture to a much larger port count.

Gender differences in negative affect during acute tobacco abstinence differ between African American and White adult cigarette smokers.

PubMed

Pang, Raina D; Bello, Mariel S; Liautaud, Madalyn M; Weinberger, Andrea H; Leventhal, Adam M

2018-06-15

Prior studies have found heightened negative affect following tobacco abstinence in women compared to men. However, experimental work addressing whether these findings generalize across racial groups is scarce. The current study investigated whether race (Non-Hispanic White vs. Non-Hispanic African American) moderated gender differences in abstinence-induced negative affect and smoking behavior. Data were collected from 2010 to 2017 from two separate laboratory studies investigating experimentally manipulated tobacco abstinence. Following a baseline session, adult daily smokers (10 cigarettes per day; women: n=297, 83.8% Non-Hispanic African American; men: n=492, 86.2% Non-Hispanic African American) attended two counterbalanced lab sessions (16 hours abstinent vs. non-abstinent) and completed self-report measures of negative affect followed by a laboratory analogue smoking reinstatement task. We found a gender race interaction for several negative affect states and composite negative affect (ßs=-.12 to -.16, ps<.05). Analyses stratified by race showed that Non-Hispanic White women compared to Non-Hispanic White men exhibited greater abstinence-induced increases in anger, anxiety, and composite negative affect (ßs=-.20 to -.29, ps<.05). No significant gender differences in abstinence-induced negative affect were found for Non-Hispanic African American smokers (ßs=.00 to -.04, ps>.05). These findings suggest that negative affect during acute tobacco abstinence may be a clinically important and intervenable factor that can inform cessation interventions specifically for Non-Hispanic White women smokers. Further empirical exploration of mechanisms underlying interactions of gender and race in tobacco addiction may benefit smoking cessation efforts in Non-Hispanic African American women smokers. The current study contributes to a scant body of research examining the intersectional influence of race and gender on abstinence-induced negative affect-a central, motivationally prepotent feature of tobacco withdrawal. Using a laboratory-based design to experimentally manipulate abstinence, we provide evidence of a gender race interaction on negative affect-related withdrawal. Our findings suggest that gender differences in abstinence-induced negative affect observed among Non-Hispanic White smokers may not generalize to Non-Hispanic African American smokers, highlighting the need for future work to address potential mechanisms underlying the racially discrepant impact of gender on affective tobacco withdrawal.

Self-assembly and interactions of short antimicrobial cationic lipopeptides with membrane lipids: ITC, FTIR and molecular dynamics studies.

PubMed

Sikorska, Emilia; Dawgul, Małgorzata; Greber, Katarzyna; Iłowska, Emilia; Pogorzelska, Aneta; Kamysz, Wojciech

2014-10-01

In this work, the self-organization and the behavior of the surfactant-like peptides in the presence of biological membrane models were studied. The studies were focused on synthetic palmitic acid-containing lipopeptides, C16-KK-NH2 (I), C16-KGK-NH2 (II) and C16-KKKK-NH2 (III). The self-assembly was explored by molecular dynamics simulations using a coarse-grained force field. The critical micellar concentration was estimated by the surface tension measurements. The thermodynamics of the peptides binding to the anionic and zwitterionic lipids were established using isothermal titration calorimetry (ITC). The influence of the peptides on the lipid acyl chain ordering was determined using FTIR spectroscopy. The compounds studied show surface-active properties with a distinct CMC over the millimolar range. An increase in the steric and electrostatic repulsion between polar head groups shifts the CMC toward higher values and reduces the aggregation number. An analysis of the peptide-membrane binding revealed a unique interplay between the initial electrostatic and the subsequent hydrophobic interactions enabling the lipopeptides to interact with the lipid bilayer. In the case of C16-KKKK-NH2 (III), compensation of the electrostatic and hydrophobic interactions upon binding to the anionic membrane has been suggested and consequently no overall binding effects were noticed in ITC thermograms and FTIR spectra. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker

PubMed Central

Ta, Chau M; Adomaviciene, Aiste; Rorsman, Nils J G; Garnett, Hannah

2016-01-01

Background and Purpose Calcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. Experimental Approach Patch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. Key Results In the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. Conclusions and Implications A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID:26562072

A dependence of quasielastic charged-current neutrino-nucleus cross sections

NASA Astrophysics Data System (ADS)

Van Dessel, N.; Jachowicz, N.; González-Jiménez, R.; Pandey, V.; Van Cuyck, T.

2018-04-01

Background: 12C has been and is still widely used in neutrino-nucleus scattering and oscillation experiments. More recently, 40Ar has emerged as an important nuclear target for current and future experiments. Liquid argon time projection chambers (LArTPCs) possess various advantages in measuring electroweak neutrino-nucleus cross sections. Concurrent theoretical research is an evident necessity. Purpose: 40Ar is larger than 12C , and one expects nuclear effects to play a bigger role in reactions. We present inclusive differential and total cross section results for charged-current neutrino scattering on 40Ar and perform a comparison with 12C , 16O , and 56Fe targets, to find out about the A -dependent behavior of model predictions. Method: Our model starts off with a Hartree-Fock description of the nucleus, with the nucleons interacting through a mean field generated by an effective Skyrme force. Long-range correlations are introduced by means of a continuum random phase approximation approach. Further methods to improve the accuracy of model predictions are also incorporated in the calculations. Results: We present calculations for 12C , 16O , 40Ar , and 56Fe , showcasing differential cross sections over a broad range of kinematic values in the quasielastic regime. We furthermore show flux-folded results for 40Ar and we discuss the differences between nuclear responses. Conclusions: At low incoming energies and forward scattering we identify an enhancement in the 40Ar cross section compared to 12C , as well as in the high ω (low Tμ) region across the entire studied Eν range. The contribution to the folded cross section of the reaction strength at values of ω lower than 50 MeV for forward scattering is sizable.

Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability influenced by the substitution of Met16 in the second sphere coordination.

PubMed

Abdelhamid, Rehab F; Obara, Yuji; Kohzuma, Takamitsu

2008-01-01

Several blue copper proteins are known to change the active site structure at alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr, Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the second sphere role through alkaline transition. The visible electronic absorption and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed the increasing of axial component at pH approximately 11 like wild-type PAz. The visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that the destabilization of the protein structure was triggered at pH>11. Resonance Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys) stretching frequency was shifted to higher frequency region at pH approximately 11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu-S(Cys) bond at alkaline transition pH approximately 11. The visible electronic absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are not denatured even at pH>11. These observations suggest that Met16 is important to maintain the protein structure through the possible weak interaction between methionine -SCH3 part and coordinated histidine imidazole moiety. The introduction of pi-pi interaction in the second coordination sphere may be contributed to the enhancement of protein structure stability.

Meson exchange current (MEC) models in neutrino interaction generators

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

Katori, Teppei

2015-05-15

Understanding of the so-called 2 particle-2 hole (2p-2h) effect is an urgent program in neutrino interaction physics for current and future oscillation experiments. Such processes are believed to be responsible for the event excesses observed by recent neutrino experiments. The 2p-2h effect is dominated by the meson exchange current (MEC), and is accompanied by a 2-nucleon emission from the primary vertex, instead of a single nucleon emission from the charged-current quasi-elastic (CCQE) interaction. Current and future high resolution experiments can potentially nail down this effect. For this reason, there are world wide efforts to model and implement this process inmore » neutrino interaction simulations. In these proceedings, I would like to describe how this channel is modeled in neutrino interaction generators.« less

Charm Production in Interactions of Antiproton with Proton and Nuclei at \\bar{it{P}}it{ANDA} Energies

NASA Astrophysics Data System (ADS)

Shyam, R.; Tsushima, K.

2018-05-01

We study the production of charmed baryons in the antiproton-proton and antiproton-nucleus interactions within a fully covariant model that is based on an effective Lagrangian approach. The baryon production proceeds via the t-channel D^0 and D^{*0} meson-exchange diagrams. We have also explored the production of the charm-baryon hypernucleus ^{16}_{Λ_c^+}O in the antiproton-^{16}O collisions. For antiproton beam momenta of interest to the {\\bar{P}}ANDA experiment, the 0° differential cross sections for the formation of ^{16}_{Λ_c^+}O hypernuclear states with simple particle-hole configurations, have magnitudes in the range of a few μ b/sr.

The role of 17β-estradiol metabolites in chromium-induced oxidative stress.

PubMed

Sawicka, Ewa; Długosz, Anna

2017-01-01

The increasing incidence of estrogen-dependent breast cancer and the presence in the environment of a large number of factors that interact with estrogen receptors have sparked interest in chemical influences on estrogen-dependent processes. In a previous work, the authors examined the interaction of estradiol with chromium. In the present article the importance of estradiol biotransformation in these interactions is investigated. There is no information in the available literature about the role of metabolites in exposure to chromium. It seems important because estradiol metabolites have various carcinogenic abilities and their formation during biotransformation could be increased or decreased by environmental enzyme inducers or inhibitors. The metabolites could play a detoxifying role or create a toxic synergism in free radical processes induced by chromium VI (CrVI). The aim of this study was to evaluate the influence of 2 17β-estradiol metabolites - 4-hydroxyestradiol (4-OHE2) and 16α-hydroxyestrone (16α-OHE1) - in conditions of oxidative stress caused by CrVI. Human blood, erythrocytes or mitochondria isolated from human placentas after natural deliveries were used in the experiments. The influence of CrVI, 4-OHE2 and 16-OHE1 on thiobarbituric acid reactive substances (TBARS), the hydroxyl radical (•OH), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), and the interactions of the metabolites exposed to chromium expressed by these factors were examined. 4-OHE2 reduced the level of TBARS induced by CrVI in mitochondria (p < 0.05) and in erythrocytes (p < 0.05), and increased SOD activity (p < 0.05). 16α-OHE1 increased the activity of GST in erythrocytes exposed to CrVI (p < 0.05). The metabolites do not have toxic interactions with CrVI. On the contrary, they exhibited a protective effect. The mechanism of protection varied: 4-OHE2 decreased TBARS and increased SOD activity, while 16α-OHE1 increased GST activity.

Model Calculations with Excited Nuclear Fragmentations and Implications of Current GCR Spectra

NASA Astrophysics Data System (ADS)

Saganti, Premkumar

As a result of the fragmentation process in nuclei, energy from the excited states may also contribute to the radiation damage on the cell structure. Radiation induced damage to the human body from the excited states of oxygen and several other nuclei and its fragments are of a concern in the context of the measured abundance of the current galactic cosmic rays (GCR) environment. Nuclear Shell model based calculations of the Selective-Core (Saganti-Cucinotta) approach are being expanded for O-16 nuclei fragments into N-15 with a proton knockout and O-15 with a neutron knockout are very promising. In our on going expansions of these nuclear fragmentation model calculations and assessments, we present some of the prominent nuclei interactions from a total of 190 isotopes that were identified for the current model expansion based on the Quantum Multiple Scattering Fragmentation Model (QMSFRG) of Cucinotta. Radiation transport model calculations with the implementation of these energy level spectral characteristics are expected to enhance the understanding of radiation damage at the cellular level. Implications of these excited energy spectral calculations in the assessment of radiation damage to the human body may provide enhanced understanding of the space radiation risk assessment.

Respiratory interactions of soil bacteria with (semi)conductive iron-oxide minerals.

PubMed

Kato, Souichiro; Nakamura, Ryuhei; Kai, Fumiyoshi; Watanabe, Kazuya; Hashimoto, Kazuhito

2010-12-01

Pure-culture studies have shown that dissimilatory metal-reducing bacteria are able to utilize iron-oxide nanoparticles as electron conduits for reducing distant terminal acceptors; however, the ecological relevance of such energy metabolism is poorly understood. Here, soil microbial communities were grown in electrochemical cells with acetate as the electron donor and electrodes (poised at 0.2 V versus Ag/AgCl) as the electron acceptors in the presence and absence of iron-oxide nanoparticles, and respiratory current generation and community structures were analysed. Irrespective of the iron-oxide species (hematite, magnetite or ferrihydrite), the supplementation with iron-oxide minerals resulted in large increases (over 30-fold) in current, while only a moderate increase (∼10-fold) was observed in the presence of soluble ferric/ferrous irons. During the current generation, insulative ferrihydrite was transformed into semiconductive goethite. Clone-library analyses of 16S rRNA gene fragments PCR-amplified from the soil microbial communities revealed that iron-oxide supplementation facilitated the occurrence of Geobacter species affiliated with subsurface clades 1 and 2. We suggest that subsurface-clade Geobacter species preferentially thrive in soil by utilizing (semi)conductive iron oxides for their respiration. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

Measuring interactivity on tobacco control websites.

PubMed

Freeman, Becky; Chapman, Simon

2012-08-01

With the increased reach of Web 2.0, Internet users expect webpages to be interactive. No studies have been conducted to assess whether tobacco control-relevant sites have implemented these features. The authors conducted an analysis of an international sample of tobacco control-relevant websites to determine their level of interactivity. The sample included 68 unique websites selected from Google searches in 5 countries, on each country's Google site, using the term smoking. The 68 sites were analyzed for 10 categories of interactive tools. The most common type of interactive content found on 46 (68%) of sites was for multimedia featuring content that was not primarily text based, such as photo galleries, videos, or podcasts. Only 11 (16%) websites-outside of media sites-allowed people to interact and engage with the site owners and other users by allowing posting comments on content and/or hosting forums/discussions. Linkages to social networking sites were low: 17 pages (25%) linked to Twitter, 15 (22%) to Facebook, and 11 (16%) to YouTube. Interactivity and connectedness to online social media appears to still be in its infancy among tobacco control-relevant sites.

Purification and functional characterization of p16, the ATPase of the bacteriophage Φ29 packaging machinery

PubMed Central

Ibarra, Borja; Valpuesta, José María; Carrascosa, José L.

2001-01-01

Bacteriophage Φ29 codes for a protein (p16) that is required for viral DNA packaging both in vivo and in vitro. Co-expression of p16 with the chaperonins GroEL and GroES has allowed its purification in a soluble form. Purified p16 shows a weak ATPase activity that is stimulated by either DNA or RNA, irrespective of the presence of any other viral component. The stimulation of ATPase activity of p16, although induced under packaging conditions, is not dependent of the actual DNA packaging and in this respect the Φ29 enzyme is similar to other viral terminases. Protein p16 competes with DNA and RNA in the interaction with the viral prohead, which occurs through the N-terminal region of the connector protein (p10). In fact, p16 interacts in a nucleotide-dependent fashion with the viral Φ29-encoded RNA (pRNA) involved in DNA packaging, and this binding can be competed with DNA. Our results are consistent with a model for DNA translocation in which p16, bound and organized around the connector, acts as a power stroke to pump the DNA into the prohead, using the hydrolysis of ATP as an energy source. PMID:11691914

Purification and functional characterization of p16, the ATPase of the bacteriophage Phi29 packaging machinery.

PubMed

Ibarra, B; Valpuesta, J M; Carrascosa, J L

2001-11-01

Bacteriophage Phi29 codes for a protein (p16) that is required for viral DNA packaging both in vivo and in vitro. Co-expression of p16 with the chaperonins GroEL and GroES has allowed its purification in a soluble form. Purified p16 shows a weak ATPase activity that is stimulated by either DNA or RNA, irrespective of the presence of any other viral component. The stimulation of ATPase activity of p16, although induced under packaging conditions, is not dependent of the actual DNA packaging and in this respect the Phi29 enzyme is similar to other viral terminases. Protein p16 competes with DNA and RNA in the interaction with the viral prohead, which occurs through the N-terminal region of the connector protein (p10). In fact, p16 interacts in a nucleotide-dependent fashion with the viral Phi29-encoded RNA (pRNA) involved in DNA packaging, and this binding can be competed with DNA. Our results are consistent with a model for DNA translocation in which p16, bound and organized around the connector, acts as a power stroke to pump the DNA into the prohead, using the hydrolysis of ATP as an energy source.

Access and Use of MMS Data through SPDF Services

NASA Astrophysics Data System (ADS)

McGuire, R. E.; Bilitza, D.; Boardsen, S. A.; Candey, R. M.; Chimiak, R.; Cooper, J. F.; Garcia, L. N.; Harris, B. T.; Johnson, R. C.; Kovalick, T. J.; Lal, N.; Leckner, H. A.; Liu, M. H.; Papitashvili, N. E.; Rao, U. R.; Roberts, D. A.; Yurow, R. E.

2016-12-01

In its role as a Heliophysics Active Final Archive and in close cooperation with the MMS project and its Science Data Center, the Space Physics Data Facility (SPDF) now serves a full set of public MMS data and QuickLook plots. All SPDF services for this data and all data are available via links from the SPDF home page (http://spdf.gsfc.nasa.gov). SPDF's CDAWeb features MMS Level-2 survey and burst mode data with graphics, listing and data superset/subset functions. These capabilities are available (1) through our html user interface, (2) through calls to our CDAS web services API, and (3) through other interfaces and libraries using the CDAS web services or that otherwise access our holdings including SPDF's Heliophysics Data Portal and several external systems. As context in use of the MMS data, CDAWeb also serves current data from many other current missions. These include the Van Allen Probes 1/2 and the five THEMIS/ARTEMIS spacecraft, as well as e.g. ACE, Cluster 1/2/3/4, DMSP 16/17/18, Geotail, GOES 13/14/15, NOAA/POES 15/16/18/19, MetOP POES 1/2, Stereo A/B, TWINS 1/2, Wind and >120 Ground-Based investigations). This full set of public MMS Level-2 science data and QuickLook plots, and all other public data held by SPDF, are also available for direct file download by HTTP or FTP links from the SPDF home page above. As a reminder, MMS Level-2 data are publicly available about 30 days after data is taken, and QuickLook survey plots are available about a day after data is taken). MMS orbits (current and predictive) are served through SPDF's SSCWeb service and our Java-based interactive 4D Orbit Viewer, also with orbits of many other current missions). Our presentation will discuss recent enhancements to CDAWeb and other services and our plans to support new MMS data products and upcoming heliophysics missions including ICON, GOLD and Solar Probe Plus.

The Effects of Multivitamin Supplementation on Diurnal Cortisol Secretion and Perceived Stress

PubMed Central

Camfield, David A.; Wetherell, Mark A.; Scholey, Andrew B.; Cox, Katherine H. M.; Fogg, Erin; White, David J.; Sarris, Jerome; Kras, Marni; Stough, Con; Sali, Avni; Pipingas, Andrew

2013-01-01

Recent evidence suggests that dietary intake of vitamins, in particular the B-vitamins including B6, B9 and B12 may have a number of positive effects on mood and stress. Given the effects of stress on a range of biological mechanisms including the endocrine system, it could be reasonably expected that multivitamin supplementation may also affect markers of these mechanisms such as diurnal cortisol secretion. In the current double-blind placebo-controlled study 138 adults (aged 20 to 50 years) were administered a multivitamin containing B-vitamins versus placebo over a 16-week period. Salivary cortisol measurements were taken at waking, 15-min, 30-min and at bedtime, at baseline, 8-weeks and 16-weeks. Perceived Stress (PSS) was measured at baseline, 8-weeks and 16-weeks, while blood serum measures of B6, B12 and homocysteine (HCy) as well as red cell folate (B9) were also collected at these time points. A significant interaction was found between treatment group and study visit for the Cortisol Awakening Response (CAR). Compared to placebo, at 16-weeks multivitamin supplementation was found to be associated with a near-significant trend towards an increased CAR. No significant differences in PSS were found between groups, with PSS increasing in both groups across the course of the study. Red cell folate was found to be significantly correlated with the CAR response at 16-weeks while HCy levels were not found to be associated with the CAR response, although HCy significantly correlated with waking cortisol levels at 8-weeks. A possible interpretation of the elevation in CAR associated with multivitamin supplementation is that this represents an adaptive response to everyday demands in healthy participants. PMID:24284609

Influence of internal current and pacing current on pacemaker longevity.

PubMed

Schuchert, A; Kuck, K H

1994-01-01

The effects of lower pulse amplitude on battery current and pacemaker longevity were studied comparing the new, small-sized VVI pacemaker, Minix 8341, with the former model, Pasys 8329. Battery current was telemetrically measured at 0.8, 1.6, 2.5, and 5.0 V pulse amplitude and 0.05, 0.25, 0.5, and 1.0 msec pulse duration. Internal current was assumed to be equal to the battery current at 0.8 V and 0.05 msec. Pacing current was calculated subtracting internal current from battery current. The Minix pacemaker had a significantly lower battery current because of a lower internal current (Minix: 4.1 +/- 0.1 microA; Pasys: 16.1 +/- 0.1 microA); pacing current of both units was similar. At 0.5 msec pulse duration, the programming from 5.0-2.5 V pulse amplitude resulted in a greater relative reduction of battery current in the newer pacemaker (51% vs 25%). Projected longevity of each pacemaker was 7.9 years at 5.0 V and 0.5 msec. The programming from 5.0-2.5 V extended the projected longevity by 2.3 years (Pasys) and by 7.1 years (Minix). The longevity was negligibly longer after programming to 1.6 V. extension of pacemaker longevity can be achieved with the programming to 2.5 V or less if the connected pacemakers need a low internal current for their circuitry.

Observations and Simulations of the Impact of Wave-Current Interaction on Wave Direction in the Surf Zone

NASA Astrophysics Data System (ADS)

Hopkins, Julia; Elgar, Steve; Raubenheimer, Britt

2017-04-01

Accurately characterizing the interaction of waves and currents can improve predictions of wave propagation and subsequent sediment transport in the nearshore. Along the southern shoreline of Martha's Vineyard, MA, waves propagate across strong tidal currents as they shoal, providing an ideal environment for investigating wave-current interaction. Wave directions and mean currents observed for two 1-month-long periods in 7- and 2-m water depths along 11 km of the Martha's Vineyard shoreline have strong tidal modulations. Wave directions shift by as much as 70 degrees over a tidal cycle in 7 m depth, and by as much as 25 degrees in 2 m depth. The magnitude of the tidal modulations in the wave field decreases alongshore to the west, consistent with the observed decrease in tidal currents from 2.1 to 0.2 m/s. The observations are reproduced accurately by a numerical model (SWAN and Deflt3D-FLOW) that simulates waves and currents over the observed bathymetry. Model simulations with and without wave-current interaction and tidal depth changes demonstrate that the observed tidal modulations of the wave field primarily are caused by wave-current interaction and not by tidal changes to water depths over the nearby complex shoals. Sediment transport estimates from simulated wave conditions using a range of tidal currents and offshore wave fields indicate that the modulation of the wave field at Martha's Vineyard can impact the direction of wave-induced alongshore sediment transport, sometimes driving transport opposing the direction of the offshore incident wave field. As such, the observations and model simulations suggest the importance of wave-current interaction to tidally averaged transport in mixed-energy wave-and-current nearshore environments. Supported by ASD(R&E), NSF, NOAA (Sea Grant), and ONR.

Iron monocyanide (FeCN): Spin-orbit and vibronic interactions in low-lying electronic states

NASA Astrophysics Data System (ADS)

Jerosimić, Stanka V.; Milovanović, Milan Z.

2018-04-01

The spin-orbit eigenvalues of low-energy quartet and sextet spatially degenerate electronic states of FeCN are reported, together with the combined effect of vibronic and spin-orbit interaction in the lowest-lying 14Δ and 16Δ states of FeCN, by using perturbational and variational method. Spin-orbit constants (ASO) have been calculated in the basis of: (a) two components of each degenerate state, (b) four components of 14Δ and 14Π (16Δ and 16Π) states, and (c) ten components of 16Δ, 16Π, 16Σ+, 14Δ, 14Π, and 14Σ+ states. The present calculations predict the values of ASO= -77 cm-1 for 16Δ and ASO= -108 cm-1 for 14Δ state in the lowest-energy spin-orbit manifolds of each state. The major perturbing state for the 14Δ state is the 14Π state (16Π for the sextet 16Δ). As expected, based on extremely small splitting and shallowness of the bending potential energy curves for the lowest-lying 4,6Δ states, the present study indicate that the vibronic coupling does not create significant splitting of the bending levels, but the influence of anharmonicity in the bending mode is more pronounced. However, the spin-orbit fine structure dominantly influences the spectra of this species.

The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion.

PubMed

Koenen, Andrea; Babendreyer, Aaron; Schumacher, Julian; Pasqualon, Tobias; Schwarz, Nicole; Seifert, Anke; Deupi, Xavier; Ludwig, Andreas; Dreymueller, Daniela

2017-01-01

The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis.

The DRF motif of CXCR6 as chemokine receptor adaptation to adhesion

PubMed Central

Koenen, Andrea; Babendreyer, Aaron; Schumacher, Julian; Pasqualon, Tobias; Schwarz, Nicole; Seifert, Anke; Deupi, Xavier

2017-01-01

The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling. In this work, modeling analyses revealed that the phenylalanine F3.51 in CXCR6 might have impact on intramolecular interactions including hydrogen bonds by this possibly changing receptor function. Initial investigations with embryonic kidney HEK293 cells and further studies with monocytic THP-1 cells showed that mutation of DRF into DRY does not influence ligand binding, receptor internalization, receptor recycling, and protein kinase B (AKT) signaling. Adhesion was slightly decreased in a time-dependent manner. However, CXCL16-induced calcium signaling and migration were increased. Vice versa, when the DRY motif of the related receptor CX3CR1 was mutated into DRF the migratory response towards CX3CL1 was diminished, indicating that the presence of a DRF motif generally impairs chemotaxis in chemokine receptors. Transmembrane and soluble CXCL16 play divergent roles in homeostasis, inflammation, and cancer, which can be beneficial or detrimental. Therefore, the DRF motif of CXCR6 may display a receptor adaptation allowing adhesion and cell retention by transmembrane CXCL16 but reducing the chemotactic response to soluble CXCL16. This adaptation may avoid permanent or uncontrolled recruitment of inflammatory cells as well as cancer metastasis. PMID:28267793

Cross sections for production of the 15.10 MeV and other astrophysically significant gamma-ray lines through excitation and spallation of sup 12 C and sup 16 O with protons

NASA Technical Reports Server (NTRS)

Lang, F. L.; Werntz, C. W.; Crannell, C. J.; Trombka, J. I.; Chang, C. C.

1986-01-01

The ratio of the flux of 15.10-MeV gamma rays to the flux of 4.438-MeV gamma rays resulting from excitation of the corresponding states in C-12 as a sensitive measure of the spectrum of the exciting particles produced in solar flares and other cosmic sources. These gamma rays are produced predominantly by interactions with C-12 and O-16, both of which are relatively abundant in the solar photosphere. Gamma ray production cross sections for proton interactions have been reported previously for all important channels except for the production of 15.10-MeV gamma rays from O-16. The first reported measurement of the 15.10-MeV gamma ray production cross section from p + O-16 is presented here. The University of Maryland cyclotron was employed to produce 40-, 65-, and 86-MeV protons which interacted with CH2 and BeO targets. The resultant gamma ray spectra were measured with a high-purity germanium semiconductor detector at 70, 90, 110, 125, and 140 degrees relative to the direction of the incident beam for each proton energy. Other gamma ray lines resulting from direct excitation and spallation reactions with C-12 and 0-16 were observed as well, and their gamma ray production cross sections described.

Pharmacist-Patient Interaction and Patient Expectations

ERIC Educational Resources Information Center

DeSimone, Edward M.; And Others

1977-01-01

The nature of the professional interaction between the pharmacist and the patient was explored, with data collected from 3,743 questions asked of 16 pharmacists during an 8-week period. Factors that might affect the nature of the pharmacist-patient interaction are identified along with a cognitive-based profile of patient wants. (LBH)

50 CFR 230.1 - Purpose and scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... Provisions of the Marine Mammal Protection Act of 1972 (16 U.S.C. 1361 et seq.) and the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) also pertain to human interactions with whales. Rules elsewhere... in this part is to implement the Whaling Convention Act (16 U.S.C. 916 et seq.) by prohibiting...

50 CFR 230.1 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Provisions of the Marine Mammal Protection Act of 1972 (16 U.S.C. 1361 et seq.) and the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) also pertain to human interactions with whales. Rules elsewhere... in this part is to implement the Whaling Convention Act (16 U.S.C. 916 et seq.) by prohibiting...

50 CFR 230.1 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... Provisions of the Marine Mammal Protection Act of 1972 (16 U.S.C. 1361 et seq.) and the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) also pertain to human interactions with whales. Rules elsewhere... in this part is to implement the Whaling Convention Act (16 U.S.C. 916 et seq.) by prohibiting...

50 CFR 230.1 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Provisions of the Marine Mammal Protection Act of 1972 (16 U.S.C. 1361 et seq.) and the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) also pertain to human interactions with whales. Rules elsewhere... in this part is to implement the Whaling Convention Act (16 U.S.C. 916 et seq.) by prohibiting...

50 CFR 230.1 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... Provisions of the Marine Mammal Protection Act of 1972 (16 U.S.C. 1361 et seq.) and the Endangered Species Act of 1973 (16 U.S.C. 1531 et seq.) also pertain to human interactions with whales. Rules elsewhere... in this part is to implement the Whaling Convention Act (16 U.S.C. 916 et seq.) by prohibiting...

Traveling magnetopause distortion related to a large-scale magnetosheath plasma jet: THEMIS and ground-based observations

NASA Astrophysics Data System (ADS)

Dmitriev, A. V.; Suvorova, A. V.

2012-08-01

Here, we present a case study of THEMIS and ground-based observations of the perturbed dayside magnetopause and the geomagnetic field in relation to the interaction of an interplanetary directional discontinuity (DD) with the magnetosphere on 16 June 2007. The interaction resulted in a large-scale local magnetopause distortion of an "expansion - compression - expansion" (ECE) sequence that lasted for ˜15 min. The compression was caused by a very dense, cold, and fast high-βmagnetosheath plasma flow, a so-called plasma jet, whose kinetic energy was approximately three times higher than the energy of the incident solar wind. The plasma jet resulted in the effective penetration of magnetosheath plasma inside the magnetosphere. A strong distortion of the Chapman-Ferraro current in the ECE sequence generated a tripolar magnetic pulse "decrease - peak- decrease" (DPD) that was observed at low and middle latitudes by some ground-based magnetometers of the INTERMAGNET network. The characteristics of the ECE sequence and the spatial-temporal dynamics of the DPD pulse were found to be very different from any reported patterns of DD interactions with the magnetosphere. The observed features only partially resembled structures such as FTE, hot flow anomalies, and transient density events. Thus, it is difficult to explain them in the context of existing models.

A pilot study for robot appearance preferences among high-functioning individuals with autism spectrum disorder: Implications for therapeutic use

PubMed Central

Warren, Zachary; Muramatsu, Taro; Yoshikawa, Yuichiro; Matsumoto, Yoshio; Miyao, Masutomo; Nakano, Mitsuko; Mizushima, Sakae; Wakita, Yujin; Ishiguro, Hiroshi; Mimura, Masaru; Minabe, Yoshio; Kikuchi, Mitsuru

2017-01-01

Recent rapid technological advances have enabled robots to fulfill a variety of human-like functions, leading researchers to propose the use of such technology for the development and subsequent validation of interventions for individuals with autism spectrum disorder (ASD). Although a variety of robots have been proposed as possible therapeutic tools, the physical appearances of humanoid robots currently used in therapy with these patients are highly varied. Very little is known about how these varied designs are experienced by individuals with ASD. In this study, we systematically evaluated preferences regarding robot appearance in a group of 16 individuals with ASD (ages 10–17). Our data suggest that there may be important differences in preference for different types of robots that vary according to interaction type for individuals with ASD. Specifically, within our pilot sample, children with higher-levels of reported ASD symptomatology reported a preference for specific humanoid robots to those perceived as more mechanical or mascot-like. The findings of this pilot study suggest that preferences and reactions to robotic interactions may vary tremendously across individuals with ASD. Future work should evaluate how such differences may be systematically measured and potentially harnessed to facilitate meaningful interactive and intervention paradigms. PMID:29028837

Human spermatozoa possess a calcium-dependent chloride channel that may participate in the acrosomal reaction

PubMed Central

Orta, Gerardo; Ferreira, Gonzalo; José, Omar; Treviño, Claudia L; Beltrán, Carmen; Darszon, Alberto

2012-01-01

Motility, maturation and the acrosome reaction (AR) are fundamental functions of mammalian spermatozoa. While travelling through the female reproductive tract, spermatozoa must mature through a process named capacitation, so that they can reach the egg and undergo the AR, an exocytotic event necessary to fertilize the egg. Though Cl− is important for sperm capacitation and for the AR, not much is known about the molecular identity of the Cl− transporters involved in these processes. We implemented a modified perforated patch-clamp strategy to obtain whole cell recordings sealing on the head of mature human spermatozoa. Our whole cell recordings revealed the presence of a Ca2+-dependent Cl− current. The biophysical characteristics of this current and its sensitivity to niflumic acid (NFA) and 4,4′-diisothiocyano-2,2′-stilbene disulphonic acid (DIDIS) are consistent with those displayed by the Ca2+-dependent Cl− channel from the anoctamin family (TMEM16). Whole cell patch clamp recordings in the cytoplasmic droplet of human spermatozoa corroborated the presence of these currents, which were sensitive to NFA and to a small molecule TMEM16A inhibitor (TMEM16Ainh, an aminophenylthiazole). Importantly, the human sperm AR induced by a recombinant human glycoprotein from the zona pellucida, rhZP3, displayed a similar sensitivity to NFA, DIDS and TMEM16Ainh as the sperm Ca2+-dependent Cl− currents. Our findings indicate the presence of Ca2+-dependent Cl− currents in human spermatozoa, that TMEM16A may contribute to these currents and also that sperm Ca2+-dependent Cl− currents may participate in the rhZP3-induced AR. PMID:22473777

Biological Evaluation in Vitro and in Silico of Azetidin-2-one Derivatives as Potential Anticancer Agents.

PubMed

Olazaran, Fabián E; Rivera, Gildardo; Pérez-Vázquez, Alondra M; Morales-Reyes, Cynthia M; Segura-Cabrera, Aldo; Balderas-Rentería, Isaías

2017-01-12

Potential anticancer activity of 16 azetidin-2-one derivatives was evaluated showing that compound 6 [ N -( p -methoxy-phenyl)-2-( p -methyl-phenyl)-3-phenoxy-azetidin-2-one] presented cytotoxic activity in SiHa cells and B16F10 cells. The caspase-3 assay in B16F10 cells displayed that azetidin-2-one derivatives induce apoptosis. Microarray and molecular analysis showed that compound 6 was involved on specific gene overexpression of cytoskeleton regulation and apoptosis due to the inhibition of some cell cycle genes. From the 16 derivatives, compound 6 showed the highest selectivity to neoplastic cells, it was an inducer of apoptosis, and according to an in silico analysis of chemical interactions with colchicine binding site of human α/β-tubulin, the mechanism of action could be a molecular interaction involving the amino acids outlining such binding site.

Biological Evaluation in Vitro and in Silico of Azetidin-2-one Derivatives as Potential Anticancer Agents

PubMed Central

2016-01-01

Potential anticancer activity of 16 azetidin-2-one derivatives was evaluated showing that compound 6 [N-(p-methoxy-phenyl)-2-(p-methyl-phenyl)-3-phenoxy-azetidin-2-one] presented cytotoxic activity in SiHa cells and B16F10 cells. The caspase-3 assay in B16F10 cells displayed that azetidin-2-one derivatives induce apoptosis. Microarray and molecular analysis showed that compound 6 was involved on specific gene overexpression of cytoskeleton regulation and apoptosis due to the inhibition of some cell cycle genes. From the 16 derivatives, compound 6 showed the highest selectivity to neoplastic cells, it was an inducer of apoptosis, and according to an in silico analysis of chemical interactions with colchicine binding site of human α/β-tubulin, the mechanism of action could be a molecular interaction involving the amino acids outlining such binding site. PMID:28105271

Interactions of 13. 6-GeV/nucleon [sup 16]O and [sup 28]Si with carbon, aluminum, and copper

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

Cumming, J.B.; Chu, Y.Y.; Haustein, P.E.

1993-10-01

Cross sections for forming [sup 24]Na and [sup 18]F by the interactions of 13.6-GeV/nucleon [sup 16]O and [sup 28]Si ions with Al and for forming [sup 24]Na in [sup 16]O interactions with Cu have been measured relative to the cross section for forming [sup 11]C from carbon. The results are generally consistent with energy-independent inclusive cross sections (limiting fragmentation) for heavy ions between [similar to]2 and 13.6 GeV/nucleon. However, comparison of the heavy-ion data with those for high-energy protons indicates a significantly weaker dependence on projectile size than that predicted by the factorization hypothesis for [sigma][sub C]([sup 11]C), [sigma][sub Al]([supmore » 18]F), and [sigma][sub Al]([sup 24]Na). The dependence is slightly stronger in the case of [sigma][sub Cu]([sup 24]Na).« less

Interaction of cationic phthalocyanines with DNA. Importance of the structure of the substituents.

PubMed

López Zeballos, N C; Gauna, G A; García Vior, M C; Awruch, J; Dicelio, L E

2014-07-05

The interaction of novel zinc (II) cationic phthalocyanines with CT-DNA was studied using absorption and fluorescence spectroscopy, as well as thermal denaturation profiles. Results showed an electrostatic interaction between the phthalocyanines and CT-DNA. The properties of these phthalocyanines were compared taking the structure of the macrocycle peripheral substituents into account. 2,9(10),16(17),23(24)-tetrakis[(N-butyl-N-methylammonium)ethylsulfanyl]phthalocyaninatozinc(II) tetraiodide (Pc6) had a greater affinity for the CT-DNA helix than its bioisoster 2,9(10),16(17),23(24)-tetrakis[(N-dibutyl-N-methylammonium)ethoxy]phthalocyaninatozinc(II) tetraiodide (Pc7). 2,9(10),16(17),23(24)-tetrakis[(2-trimethylammonium)ethyl-sulfanyl]phthalocyaninatozinc(II) tetraiodide (Pc13) also carried a sulfur atom like Pc6, but linked to bulky substituents such as trimethylammonium groups. The planar aromatic region of the cationic phthalocyanines in this study appears to be unable to facilitate their intercalation with CT-DNA. Copyright © 2014 Elsevier B.V. All rights reserved.

Prediction of peer-rated adult hostility from autonomy struggles in adolescent–family interactions

PubMed Central

ALLEN, JOSEPH P.; HAUSER, STUART T.; O’CONNOR, THOMAS G.; BELL, KATHY L.

2006-01-01

Observed parent–adolescent autonomy struggles were assessed as potential predictors of the development of peer-rated hostility over a decade later in young adulthood in both normal and previously psychiatrically hospitalized groups of adolescents. Longitudinal, multireporter data were obtained by coding family interactions involving 83 adolescents and their parents at age 16 years and then obtaining ratings by close friends of adolescents’ hostility at age 25 years. Fathers’ behavior undermining adolescents’ autonomy in interactions at age 16 years were predictive of adolescents-as-young-adults’ hostility, as rated by close friends at age 25 years. These predictions contributed additional variance to understanding young adult hostility even after accounting for concurrent levels of adolescent hostility at age 16 years and paternal hostility at this age, each of which also significantly contributed to predicting future hostility. Results are discussed as highlighting a pathway by which difficulties attaining autonomy in adolescence may presage the development of long-term difficulties in social functioning. PMID:11893089

Current correlations for the transport of interacting electrons through parallel quantum dots in a photon cavity

NASA Astrophysics Data System (ADS)

Gudmundsson, Vidar; Abdullah, Nzar Rauf; Sitek, Anna; Goan, Hsi-Sheng; Tang, Chi-Shung; Manolescu, Andrei

2018-06-01

We calculate the current correlations for the steady-state electron transport through multi-level parallel quantum dots embedded in a short quantum wire, that is placed in a non-perfect photon cavity. We account for the electron-electron Coulomb interaction, and the para- and diamagnetic electron-photon interactions with a stepwise scheme of configuration interactions and truncation of the many-body Fock spaces. In the spectral density of the temporal current-current correlations we identify all the transitions, radiative and non-radiative, active in the system in order to maintain the steady state. We observe strong signs of two types of Rabi oscillations.

Jet-Surface Interaction Noise from High-Aspect Ratio Nozzles: Test Summary

NASA Technical Reports Server (NTRS)

Brown, Clifford; Podboy, Gary

2017-01-01

Noise and flow data have been acquired for a 16:1 aspect ratio rectangular nozzle exhausting near a simple surface at the NASA Glenn Research Center as part of an ongoing effort to understand, model, and predict the noise produced by current and future concept aircraft employing a tightly integrated engine airframe designs. The particular concept under consideration in this experiment is a blended-wing-body airframe powered by a series of electric fans exhausting through slot nozzle over an aft deck. The exhaust Mach number and surface length were parametrically varied during the test. Far-field noise data were acquired for all nozzle surface geometries and exhaust flow conditions. Phased-array noise source localization data and in-flow pressure data were also acquired for a subset of the isolated (no surface) and surface configurations; these measurements provide data that have proven useful for modeling the jet-surface interaction noise source and the surface effect on the jet-mixing noise in round jets. A summary of the nozzle surface geometry, flow conditions tested, and data collected are presented.

The Fibroblast Growth Factor 14·Voltage-gated Sodium Channel Complex Is a New Target of Glycogen Synthase Kinase 3 (GSK3)*

PubMed Central

Shavkunov, Alexander S.; Wildburger, Norelle C.; Nenov, Miroslav N.; James, Thomas F.; Buzhdygan, Tetyana P.; Panova-Elektronova, Neli I.; Green, Thomas A.; Veselenak, Ronald L.; Bourne, Nigel; Laezza, Fernanda

2013-01-01

The FGF14 protein controls biophysical properties and subcellular distribution of neuronal voltage-gated Na+ (Nav) channels through direct binding to the channel C terminus. To gain insights into the dynamic regulation of this protein/protein interaction complex, we employed the split luciferase complementation assay to screen a small molecule library of kinase inhibitors against the FGF14·Nav1.6 channel complex and identified inhibitors of GSK3 as hits. Through a combination of a luminescence-based counter-screening, co-immunoprecipitation, patch clamp electrophysiology, and quantitative confocal immunofluorescence, we demonstrate that inhibition of GSK3 reduces the assembly of the FGF14·Nav channel complex, modifies FGF14-dependent regulation of Na+ currents, and induces dissociation and subcellular redistribution of the native FGF14·Nav channel complex in hippocampal neurons. These results further emphasize the role of FGF14 as a critical component of the Nav channel macromolecular complex, providing evidence for a novel GSK3-dependent signaling pathway that might control excitability through specific protein/protein interactions. PMID:23640885

Adsorption of Nanoplastics on Algal Photosynthesis

NASA Astrophysics Data System (ADS)

Turner, James; Bhattacharya, Priyanka; Lin, Sijie; Ke, Pu Chun

2010-03-01

The rapid accumulation of disposed plastics in the environment, especially in the Pacific Ocean, has become a global concern in recent years. Photo, chemical and physical degradations constantly fragment these plastics into a wide array of macroscopic to microscopic particles. As a result, marine organisms such as algae may be exposed to plastic particles through ingestion, adsorption and other forms of uptake. Such interactions, currently little understood, could potentially impact on the health state of the entire food chain. Here we report on polystyrene-algae interaction and its impact on algal photosynthesis. We first investigated the adsorption of polystyrene beads (20 nm) on a cellulose film coated on a 96-well plate. We derived a supralinear increase of the adsorption with the beads concentration for both positively and negatively charged polystyrene beads, with a saturation observed for the negatively charged polystyrene beads of concentration above 1.6 mg/mL. Using a bicarbonate indicator we discovered decreased carbon dioxide depletion due to polystyrene-algae binding. Since polystyrene beads also mediated algae aggregation, nanoplastics may alternatively be harnessed for waste water treatment.

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

Volkas, R. R.; Foot, R.; He, X.

The universal QCD color theory is extended to an SU(3)/sub 1//direct product/SU(3)/sub 2//direct product/SU(3)/sub 3/ gauge theory, where quarks of the /ital i/th generation transform as triplets under SU(3)/sub /ital i// and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamentalmore » issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements.« less

Swarm observations of field-aligned currents associated with pulsating auroral patches

NASA Astrophysics Data System (ADS)

Gillies, D. M.; Knudsen, D.; Spanswick, E.; Donovan, E.; Burchill, J.; Patrick, M.

2015-11-01

We have performed a superposed epoch study of in situ field-aligned currents located near the edges of regions of pulsating aurora observed simultaneously using ground-based optical data from the Time History of Events and Macroscale Interactions during Substorms (THEMIS) all-sky imager (ASI) network and magnetometers on board the Swarm satellites. A total of nine traversals of Swarm over regions of pulsating aurora identified using THEMIS ASI were studied. We determined that in the cases where a clear boundary can be identified, strong downward currents are seen just poleward and equatorward of the pulsating patches. A downward current in the range of ~1-6 μA/m2 can be seen just poleward of the boundary. A weaker upward current of ~1-3 μA/m2 is observed throughout the interior of the patch. These observations indicate that currents carried by precipitating electrons within patches could close through horizontal currents and be returned at the edges, in agreement with Oguti and Hayashi (1984) and Hosokawa et al. (2010b). In addition to confirming these earlier results and adding to their statistical significance, the contribution of this study is to quantify the upward and downward current magnitudes, in some cases using two satellites traversing the same pulsating regions. Finally, we compare Swarm's two-satellite field-aligned current product to the single-satellite results and determine that the data product can be compromised in regions of pulsating aurora, a phenomenon that occurs over widespread regions and tends to persist for long periods of time. These results underscore the importance of electrical coupling between the ionosphere and magnetosphere in regions of patchy pulsating aurora.

Structure and stability of small Li2 +(X2Σ+ g )-Xen (n = 1-6) clusters

NASA Astrophysics Data System (ADS)

Saidi, Sameh; Ghanmi, Chedli; Berriche, Hamid

2014-04-01

We have studied the structure and stability of the Li2 +(X2Σ+ g )Xe n ( n = 1-6) clusters for special symmetry groups. The potential energy surfaces of these clusters, are described using an accurate ab initio approach based on non-empirical pseudopotential, parameterized l-dependent polarization potential and analytic potential forms for the Li+Xe and Xe-Xe interactions. The pseudopotential technique has reduced the number of active electrons of Li2 +(X2Σ+ g )-Xe n ( n = 1-6) clusters to only one electron, the Li valence electron. The core-core interactions for Li+Xe are included using accurate CCSD(T) potential fitted using the analytical form of Tang and Toennies. For the Xe-Xe potential interactions we have used the analytical form of Lennard Jones (LJ6 - 12). The potential energy surfaces of the Li2 +(X2Σ+ g )Xe n ( n = 1-6) clusters are performed for a fixed distance of the Li2 +(X2Σ+ g ) alkali dimer, its equilibrium distance. They are used to extract information on the stability of the Li2 +(X2Σ+ g Xe n ( n = 1-6) clusters. For each n, the stability of the different isomers is examined by comparing their potential energy surfaces. Moreover, we have determined the quantum energies ( D 0), the zero-point-energies (ZPE) and the ZPE%. To our best knowledge, there are neither experimental nor theoretical works realized for the Li2 +(X2Σ+ g Xe n ( n = 1-6) clusters, our results are presented for the first time.

Post-Newtonian evolution of massive black hole triplets in galactic nuclei - III. A robust lower limit to the nHz stochastic background of gravitational waves

NASA Astrophysics Data System (ADS)

Bonetti, Matteo; Sesana, Alberto; Barausse, Enrico; Haardt, Francesco

2018-06-01

Inspiraling massive black hole binaries (MBHBs) forming in the aftermath of galaxy mergers are expected to be the loudest gravitational-wave (GW) sources relevant for pulsar-timing arrays (PTAs) at nHz frequencies. The incoherent overlap of signals from a cosmic population of MBHBs gives rise to a stochastic GW background (GWB) with characteristic strain around hc ˜ 10-15 at a reference frequency of 1 yr-1, although uncertainties around this value are large. Current PTAs are piercing into the GW amplitude range predicted by MBHB-population models, but no detection has been reported so far. To assess the future success prospects of PTA experiments, it is therefore important to estimate the minimum GWB level consistent with our current understanding of the formation and evolution of galaxies and massive black holes (MBHs). To this purpose, we couple a semi-analytic model of galaxy evolution and an extensive study of the statistical outcome of triple MBH interactions. We show that even in the most pessimistic scenario where all MBHBs stall before entering the GW-dominated regime, triple interactions resulting from subsequent galaxy mergers inevitably drive a considerable fraction of the MBHB population to coalescence. At frequencies relevant for PTA, the resulting GWB is only a factor of 2-3 suppressed compared to a fiducial model where binaries are allowed to merge over Gyr time-scales . Coupled with current estimates of the expected GWB amplitude range, our findings suggest that the minimum GWB from cosmic MBHBs is unlikely to be lower than hc ˜ 10-16 (at f = 1 yr-1), well within the expected sensitivity of projected PTAs based on future observations with FAST, MeerKAT, and SKA.

Ultraviolet Light Curves of Gaia16apd in Superluminous Supernova Models

NASA Astrophysics Data System (ADS)

Tolstov, Alexey; Zhiglo, Andrey; Nomoto, Ken'ichi; Sorokina, Elena; Kozyreva, Alexandra; Blinnikov, Sergei

2017-08-01

Observations of Gaia16apd revealed extremely luminous ultraviolet emission among superluminous supernovae (SLSNe). Using radiation hydrodynamics simulations, we perform a comparison of UV light curves, color temperatures, and photospheric velocities between the most popular SLSN models: pair-instability supernova, magnetar, and interaction with circumstellar medium. We find that the interaction model is the most promising to explain the extreme UV luminosity of Gaia16apd. The differences in late-time UV emission and in color evolution found between the models can be used to link an observed SLSN event to the most appropriate model. Observations at UV wavelengths can be used to clarify the nature of SLSNe and more attention should be paid to them in future follow-up observations.

Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort.

PubMed

Graff, M; North, K E; Richardson, A S; Young, K M; Mohlke, K L; Lange, L A; Lange, E M; Harris, K M; Gordon-Larsen, P

2013-12-01

There has been little investigation of gene-by-environment interactions related to sedentary behaviour, a risk factor for obesity defined as leisure screen time (ST; i.e. television, video and computer games). To test the hypothesis that limiting ST use attenuates the genetic predisposition to increased body mass index (BMI), independent of physical activity. Using 7642 wave II participants of the National Longitudinal Study of Adolescent Health, (Add Health; mean = 16.4 years, 52.6% female), we assessed the interaction of ST (h week(-1) ) and 41 established obesity single nucleotide polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European-American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA) adolescents. Nominally significant SNP*ST interaction were found for FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE] = 0.016[0.007]), AA: beta [SE] = 0.016[0.011]) per 7 h week(-1) ST and one risk allele in relation to BMI Z-score. While for two established BMI loci, we find evidence that high levels of ST exacerbate the influence of obesity susceptibility variants on body mass; overall, we do not find strong evidence for interactions between the majority of established obesity loci. However, future studies with larger sample sizes, or that may build on our current study and the growing published literature, are clearly warranted. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

The clinician's guide to autism.

PubMed

Harrington, John W; Allen, Korrie

2014-02-01

On the basis of the most recent epidemiologic research, Autism Spectrum Disorder (ASD) affects approximately 1% to 2% of all children. (1)(2) On the basis of some research evidence and consensus, the Modified Checklist for Autism in Toddlers isa helpful tool to screen for autism in children between ages 16 and 30 months. (11) The Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, changes to a 2-symptom category from a 3-symptom category in the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition(DSM-5): deficits in social communication and social interaction are combined with repetitive and restrictive behaviors, and more criteria are required per category. The DSM-5 subsumes all the previous diagnoses of autism (classic autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified) into just ASDs. On the basis of moderate to strong evidence, the use of applied behavioral analysis and intensive behavioral programs has a beneficial effect on language and the core deficits of children with autism. (16) Currently, minimal or no evidence is available to endorse most complementary and alternative medicine therapies used by parents, such as dietary changes (gluten free), vitamins, chelation, and hyperbaric oxygen. (16) On the basis of consensus and some studies, pediatric clinicians should improve their capacity to provide children with ASD a medical home that is accessible and provides family-centered, continuous, comprehensive and coordinated, compassionate, and culturally sensitive care. (20)

Optical and Terahertz Measurements of Spintronic Materials

NASA Astrophysics Data System (ADS)

Bas, Derek A.

Terahertz time-domain spectroscopy (THz-TDS) is a versatile method to determine lattice, electronic charge and spin dynamics. This dissertation employs THz-TDS to study the spin and charge dynamics in topological insulator and antiferromagnetic systems. Observing time-domain effects on the scale of picoseconds gives unprecedented control over optoelectronic properties. Methods and challenges of THz generation, detection, and transmission are outlined. The wealth of light-matter interactions present in all nonlinear optical experiments are discussed, including primarily optical rectification, shift currents, and injection currents. Each of these gives valuable insight into the carrier dynamics of a material type. Conventional electronics can be improved in their speed and efficiency by taking advantage of an additional degree of freedom- electron spin. Therefore, we consider material types which exhibit great potential to replace common electronic materials while simultaneously employing electron spin for information storage or transport. Antiferromagnets show a type of spin-order that has the ability to store bits without unwanted interactions between neighboring particles. In antiferromagnetic MnF2 which has a Neel temperature of TN = 67 K, THz-TDS is performed on one-magnon and two-magnon resonances in the 0.1-2.3 THz range while varying the temperature from 6 to 295 K. The behavior of the one-magnon resonance is modeled by modified molecular field theory with an additional coupling term j set as a free parameter to fit the data. The resulting best fit value j = 1.1 provides the first experimental evidence indicating that neighboring spins in MnF 2 are only weakly coupled, closely approximating mean-field theory. Time-of-flight analysis was performed on the transmitted THz pulses to measure the temperature-dependent THz refractive index, which was modeled by phonon energy in the T > TN regime and magnetic energy in the T < TN regime. In the range T < 10 K, measured data deviates from this theory, and can be modeled by internal energy from hyperfine interactions, providing the first direct observation of hyperfine interactions in THz spectroscopy. Topological insulators exhibit the ability to transport spin-polarized currents along their surfaces with high mobilities. Phase-related pulses at photon energies 0.8 and 1.6 eV are used to simultaneously inject shift and injection currents into thin-films of the prototypical topological insulator Bi2Se3, and the foundation is laid out for an extensive study of the novel carrier properties in topological surface states. A method of symmetry analysis based on the crystal lattice is developed for isolation and individual study of the surfaceonly shift currents, which are threefold symmetric with equal components parallel and perpendicular to the pump polarization, and bulk/surface injection currents, which are isotropic parallel to the pump polarization and vanishing perpendicular to it. Pump energies can be tuned through the Dirac point, a capability which holds promise for the search of smoking gun evidence for the novel topological insulator surface state behavior that has been theorized.

Structure of a Potential Therapeutic Antibody Bound to Interleukin-16 (IL-16)

PubMed Central

Hall, Gareth; Cullen, Eilish; Sawmynaden, Kovilen; Arnold, Joanne; Fox, Simon; Cowan, Richard; Muskett, Frederick W.; Matthews, David; Merritt, Andrew; Kettleborough, Catherine; Cruikshank, William; Taylor, Debra; Bayliss, Richard; Carr, Mark D.

2016-01-01

Interleukin-16 (IL-16) is reported to be a chemoattractant cytokine and modulator of T-cell activation, and has been proposed as a ligand for the co-receptor CD4. The secreted active form of IL-16 has been detected at sites of TH1-mediated inflammation, such as those seen in autoimmune diseases, ischemic reperfusion injury (IRI), and tissue transplant rejection. Neutralization of IL-16 recruitment to its receptor, using an anti-IL16 antibody, has been shown to significantly attenuate inflammation and disease pathology in IRI, as well as in some autoimmune diseases. The 14.1 antibody is a monoclonal anti-IL-16 antibody, which when incubated with CD4+ cells is reported to cause a reduction in the TH1-type inflammatory response. Secreted IL-16 contains a characteristic PDZ domain. PDZ domains are typically characterized by a defined globular structure, along with a peptide-binding site located in a groove between the αB and βB structural elements and a highly conserved carboxylate-binding loop. In contrast to other reported PDZ domains, the solution structure previously reported for IL-16 reveals a tryptophan residue obscuring the recognition groove. We have solved the structure of the 14.1Fab fragment in complex with IL-16, revealing that binding of the antibody requires a conformational change in the IL-16 PDZ domain. This involves the rotation of the αB-helix, accompanied movement of the peptide groove obscuring tryptophan residue, and consequent opening up of the binding site for interaction. Our study reveals a surprising mechanism of action for the antibody and identifies new opportunities for the development of IL-16-targeted therapeutics, including small molecules that mimic the interaction of the antibody. PMID:27231345

Potential risk of esophageal squamous cell carcinoma due to nucleotide excision repair XPA and XPC gene variants and their interaction among themselves and with environmental factors.

PubMed

Rafiq, Rumaisa; Bhat, Gulzar Ahmad; Lone, Mohd Maqbool; Masood, Akbar; Dar, Nazir Ahmad

2016-08-01

The association of nucleotide excision repair (NER) gene polymorphisms with esophageal squamous cell carcinoma (ESCC) is inconclusive. The aim of the current study was to assess the association of repair gene xeroderma pigmentosum A (XPA) (rs-1800975) and xeroderma pigmentosum C (XPC) (rs-2228000) polymorphisms with ESCC risk as well as modifying effects of environmental factors. The genotyping was done in 450 confirmed ESCC cases and equal number of individually matched controls by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and direct sequencing methods. Conditional logistic regression models were used to assess the genotypic associations and interactions. A high ESCC risk was found in subjects who carried the homozygous minor allele of XPA (odds ratio (OR) = 3.57; 95 % confidence interval (CI) = 1.76-7.23), and the risk was higher when analysis was limited to participants who were ever smokers (OR = 4.22; 95 % CI = 2.01-8.88), lived in adobe houses (OR = 8.42; 95 % CI = 3.74-18.95), consumed large volumes of salt tea (OR = 7.42; 95 % CI = 3.30-16.69), or had a positive family history of cancer (FHC) (OR = 9.47; 95 % CI = 4.67-19.20). In case of XPC, a homozygous minor allele also showed strong association with ESCC risk (OR = 4.43; 95 % CI = 2.41-8.16). We again observed a very strong effect of the above environmental factors in elevating the risk of ESCC. Further, the variant genotypes of both genes in combination showed an increased risk towards ESCC (OR = 7.01; 95 % CI = 3.14-15.64) and such association was synergistically significant. Salt tea consumption showed an interaction with genotypes of XPA and XPC. However, an interaction with FHC was significant in the case of XPA genotype only. XPA and XPC genotypes are associated with an increased risk of ESCC, and such association was reasonably modulated by different exposures.

Cyanobacterial endobionts within a major marine planktonic calcifier (Globigerina bulloides, Foraminifera) revealed by 16S rRNA metabarcoding

NASA Astrophysics Data System (ADS)

Bird, Clare; Darling, Kate F.; Russell, Ann D.; Davis, Catherine V.; Fehrenbacher, Jennifer; Free, Andrew; Wyman, Michael; Ngwenya, Bryne T.

2017-02-01

We investigated the possibility of bacterial symbiosis in Globigerina bulloides, a palaeoceanographically important, planktonic foraminifer. This marine protist is commonly used in micropalaeontological investigations of climatically sensitive subpolar and temperate water masses as well as wind-driven upwelling regions of the world's oceans. G. bulloides is unusual because it lacks the protist algal symbionts that are often found in other spinose species. In addition, it has a large offset in its stable carbon and oxygen isotopic compositions compared to other planktonic foraminifer species, and also that predicted from seawater equilibrium. This is suggestive of novel differences in ecology and life history of G. bulloides, making it a good candidate for investigating the potential for bacterial symbiosis as a contributory factor influencing shell calcification. Such information is essential to evaluate fully the potential response of G. bulloides to ocean acidification and climate change. To investigate possible ecological interactions between G. bulloides and marine bacteria, 18S rRNA gene sequencing, fluorescence microscopy, 16S rRNA gene metabarcoding and transmission electron microscopy (TEM) were performed on individual specimens of G. bulloides (type IId) collected from two locations in the California Current. Intracellular DNA extracted from five G. bulloides specimens was subjected to 16S rRNA gene metabarcoding and, remarkably, 37-87 % of all 16S rRNA gene sequences recovered were assigned to operational taxonomic units (OTUs) from the picocyanobacterium Synechococcus. This finding was supported by TEM observations of intact Synechococcus cells in both the cytoplasm and vacuoles of G. bulloides. Their concentrations were up to 4 orders of magnitude greater inside the foraminifera than those reported for the California Current water column and approximately 5 % of the intracellular Synechococcus cells observed were undergoing cell division. This suggests that Synechococcus is an endobiont of G. bulloides type IId, which is the first report of a bacterial endobiont in the planktonic foraminifera. We consider the potential roles of Synechococcus and G. bulloides within the relationship and the need to determine how widespread the association is within the widely distributed G. bulloides morphospecies. The possible influence of Synechococcus respiration on G. bulloides shell geochemistry is also explored.

On wind-wave-current interactions during the Shoaling Waves Experiment

NASA Astrophysics Data System (ADS)

Zhang, Fei W.; Drennan, William M.; Haus, Brian K.; Graber, Hans C.

2009-01-01

This paper presents a case study of wind-wave-current interaction during the Shoaling Waves Experiment (SHOWEX). Surface current fields off Duck, North Carolina, were measured by a high-frequency Ocean Surface Current Radar (OSCR). Wind, wind stress, and directional wave data were obtained from several Air Sea Interaction Spar (ASIS) buoys moored in the OSCR scanning domain. At several times during the experiment, significant coastal currents entered the experimental area. High horizontal shears at the current edge resulted in the waves at the peak of wind-sea spectra (but not those in the higher-frequency equilibrium range) being shifted away from the mean wind direction. This led to a significant turning of the wind stress vector away from the mean wind direction. The interactions presented here have important applications in radar remote sensing and are discussed in the context of recent radar imaging models of the ocean surface.

Development of generic calcium imaging assay for monitoring Gi-coupled receptors and G-protein interaction.

PubMed

Ueda, Takashi; Ugawa, Shinya; Ishida, Yusuke; Hondoh, Aki; Shimada, Shoichi

2009-08-01

G-protein-coupled receptors (GPCRs) are important therapeutic targets for many areas of drug research and development. Although chimeric Galpha16 proteins are valuable tools for detecting the activation of Galpha(i/o)-coupled receptors, the details of the activation process remain unclear. The authors introduce a series of chimeras that combine both Galpha16 and Galpha(i/o) (Galpha(16/o), Galpha(16/i2), and Galpha(16/i3)) into a well-established transient expression system to examine the ability of these chimeras to interact with D2 long-form (D2L) dopamine and 5-HT1A serotonin receptors. The pEC50 data obtained for known agonists were similar to results from previous studies that used other cell-based assays, thus indicating sufficient sensitivity for the assay. Moreover, quinpirole exhibited similar intrinsic activity to dopamine at the D2L receptor, whereas S-(-)-3-PPP displayed partial activity of dopamine and quinpirole in the presence of the Galpha(16/o) chimera. The potency of dopamine for D2L receptors was similar among Galpha(16/o), Galpha(16/i2), and Galpha(16/i3). In contrast, the 5-HT1A receptor exhibited a significantly preferential coupling for Galpha(16/i3) compared with Galpha(16/i2) when serotonin was used as a ligand. This finding was in close agreement with the results of previous reports. The present system could therefore be used as a rapid functional assay for high-throughput screening and deorphanization.

The Importance of High-Risk Human Papillomavirus Types Other Than 16 and 18 in Cervical Neoplasia.

PubMed

Robadi, Ibrahim A; Pharaon, Majed; Ducatman, Barbara S

2018-06-01

- Types 16 and 18 are the most widely studied high-risk types of human papillomavirus (HPV). However, other high-risk HPV types (HPV non-16/18) also play a significant role in cervical neoplasia. Currently, screening and management algorithms separate out HPV 16/18 from all other HPV non-16/18 types. In addition, most of the previously vaccinated population has only been vaccinated for these high-risk types, so many women are still vulnerable to HPV non-16/18 infections. - To review the prevalence and role of HPV non-16/18 neoplasia and to review current surveillance, management, and vaccination strategies in view of these findings. - The study comprised a review of the literature. - Although HPV non-16/18 types are less frequently associated with cervical intraepithelial neoplasia and cancer, they are nonetheless a significant cause of disease. Further stratification of higher-risk HPV non-16/18 may be necessary to improve prevention and management, however, regional prevalence differences may make a unified approach difficult. As HPV 16/18 infections decrease owing to vaccination of at-risk women, the relative frequency of HPV non-16/18 will increase, although the latest vaccine covers several more high-risk types.

Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine

PubMed Central

Cadwell, Ken; Patel, Khushbu K.; Maloney, Nicole S.; Liu, Ta-Chiang; Ng, Aylwin C.Y.; Storer, Chad E.; Head, Richard D.; Xavier, Ramnik; Stappenbeck, Thaddeus S.; Virgin, Herbert W.

2010-01-01

SUMMARY It is unclear why disease occurs in only a small proportion of persons carrying common risk alleles of disease susceptibility genes. Here we demonstrate that an interaction between a specific virus infection and a mutation in the Crohn’s disease susceptibility gene Atg16L1 induces intestinal pathologies in mice. This virus-plus-susceptibility gene interaction generated abnormalities in granule packaging and unique patterns of gene expression in Paneth cells. Further, the response to injury induced by the toxic substance dextran sodium sulfate was fundamentally altered to include pathologies resembling aspects of Crohn’s disease. These pathologies triggered by virus-plus-susceptibility gene interaction were dependent on TNFα and IFNγ and were prevented by treatment with broad spectrum antibiotics. Thus, we provide a specific example of how a virus-plus-susceptibility gene interaction can, in combination with additional environmental factors and commensal bacteria, determine the phenotype of hosts carrying common risk alleles for inflammatory disease. PMID:20602997

Influence of detector collimation and beam pitch for identification and image quality of ground-glass attenuation and nodules on 16- and 64-detector row CT systems: experimental study using chest phantom.

PubMed

Ohno, Yoshiharu; Koyama, Hisanobu; Kono, Astushi; Terada, Mari; Inokawa, Hiroyasu; Matsumoto, Sumiaki; Sugimura, Kazuro

2007-12-01

The purpose of the present study was to determine the influence of detector collimation and beam pitch for identification and image quality of ground-glass attenuation (GGA) and nodules on 16- and 64-detector row CTs, by using a commercially available chest phantom. A chest CT phantom including simulated GGAs and nodules was scanned with different detector collimations, beam pitches and tube currents. The probability and image quality of each simulated abnormality was visually assessed with a five-point scoring system. ROC-analysis and ANOVA were then performed to compare the identification and image quality of either protocol with standard values. Detection rates of low-dose CTs were significantly reduced when tube currents were set at 40mA or less by using detector collimation 16 and 64x0.5mm and 16 and 32mmx1.0mm for low pitch, and at 100mA or less by using detector collimation 16 and 64x0.5mm and 16 and 32mmx1.0mm for high pitch (p<0.05). Image qualities of low-dose CTs deteriorated significantly when tube current was set at 100mA or less by using detector collimation 16 and 64x0.5mm and 16 and 32x1.0mm for low pitch, and at 150mA or less by using detector collimation 16 and 64x0.5mm and 16 and 32x1.0mm for high pitch (p<0.05). Detector collimation and beam pitch were important factors for the image quality and identification of GGA and nodules by 16- and 64-detector row CT.

A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals

PubMed Central

Angotzi, Gian Nicola; Boi, Fabio; Zordan, Stefano; Bonfanti, Andrea; Vato, Alessandro

2014-01-01

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays. PMID:25096831

Structure determination of uracil-DNA N-glycosylase from Deinococcus radiodurans in complex with DNA.

PubMed

Pedersen, Hege Lynum; Johnson, Kenneth A; McVey, Colin E; Leiros, Ingar; Moe, Elin

2015-10-01

Uracil-DNA N-glycosylase (UNG) is a DNA-repair enzyme in the base-excision repair (BER) pathway which removes uracil from DNA. Here, the crystal structure of UNG from the extremophilic bacterium Deinococcus radiodurans (DrUNG) in complex with DNA is reported at a resolution of 1.35 Å. Prior to the crystallization experiments, the affinity between DrUNG and different DNA oligonucleotides was tested by electrophoretic mobility shift assays (EMSAs). As a result of this analysis, two 16 nt double-stranded DNAs were chosen for the co-crystallization experiments, one of which (16 nt AU) resulted in well diffracting crystals. The DNA in the co-crystal structure contained an abasic site (substrate product) flipped into the active site of the enzyme, with no uracil in the active-site pocket. Despite the high resolution, it was not possible to fit all of the terminal nucleotides of the DNA complex into electron density owing to disorder caused by a lack of stabilizing interactions. However, the DNA which was in contact with the enzyme, close to the active site, was well ordered and allowed detailed analysis of the enzyme-DNA interaction. The complex revealed that the interaction between DrUNG and DNA is similar to that in the previously determined crystal structure of human UNG (hUNG) in complex with DNA [Slupphaug et al. (1996). Nature (London), 384, 87-92]. Substitutions in a (here defined) variable part of the leucine loop result in a shorter loop (eight residues instead of nine) in DrUNG compared with hUNG; regardless of this, it seems to fulfil its role and generate a stabilizing force with the minor groove upon flipping out of the damaged base into the active site. The structure also provides a rationale for the previously observed high catalytic efficiency of DrUNG caused by high substrate affinity by demonstrating an increased number of long-range electrostatic interactions between the enzyme and the DNA. Interestingly, specific interactions between residues in the N-terminus of a symmetry-related molecule and the complementary DNA strand facing away from the active site were also observed which seem to stabilize the enzyme-DNA complex. However, the significance of this observation remains to be investigated. The results provide new insights into the current knowledge about DNA damage recognition and repair by uracil-DNA glycosylases.

Role of spacer length in interaction between novel gemini imidazolium surfactants and Rhizopus oryzae lipase.

PubMed

Adak, Sunita; Datta, Sougata; Bhattacharya, Santanu; Banerjee, Rintu

2015-11-01

An insight into the effects of new ionic liquid-type gemini imidazolium cationic surfactants on the structure and function of the lipases is of prime importance for their potential application. Changes in the activity, stability and structure of Rhizopus oryzae lipase in the presence of novel gemini surfactants, [C16-3-C16im]Br2 and [C16-12-C16im]Br2 were probed in the present study. Surfactant with shorter spacer length, [C16-3-C16im]Br2 was found to be better in improving the hydrolytic activity and thermal stability of the lipase. For both the surfactants, activation was concentration dependent. CD spectroscopy results showed a decrease in α-helix and an increase in β-sheet content in the presence of these surfactants. A higher structural change observed in presence of [C16-12-C16im]Br2 correlated with lower enzyme activity. Isothermal titration calorimetric studies showed the binding to be spontaneous in nature based on sequential two site binding model. The forces involved in binding were found to differ for the two surfactants proving that the spacer length is an important factor which governs the interaction. These surfactants could be used as promising components both in enzyme modification and media engineering for attaining the desired goals in biocatalytic reactions. Copyright © 2015 Elsevier B.V. All rights reserved.

Persistent Nav1.6 current at axon initial segments tunes spike timing of cerebellar granule cells

PubMed Central

Osorio, Nancy; Cathala, Laurence; Meisler, Miriam H; Crest, Marcel; Magistretti, Jacopo; Delmas, Patrick

2010-01-01

Cerebellar granule (CG) cells generate high-frequency action potentials that have been proposed to depend on the unique properties of their voltage-gated ion channels. To address the in vivo function of Nav1.6 channels in developing and mature CG cells, we combined the study of the developmental expression of Nav subunits with recording of acute cerebellar slices from young and adult granule-specific Scn8a KO mice. Nav1.2 accumulated rapidly at early-formed axon initial segments (AISs). In contrast, Nav1.6 was absent at early postnatal stages but accumulated at AISs of CG cells from P21 to P40. By P40–P65, both Nav1.6 and Nav1.2 co-localized at CG cell AISs. By comparing Na+ currents in mature CG cells (P66–P74) from wild-type and CG-specific Scn8a KO mice, we found that transient and resurgent Na+ currents were not modified in the absence of Nav1.6 whereas persistent Na+ current was strongly reduced. Action potentials in conditional Scn8a KO CG cells showed no alteration in threshold and overshoot, but had a faster repolarization phase and larger post-spike hyperpolarization. In addition, although Scn8a KO CG cells kept their ability to fire action potentials at very high frequency, they displayed increased interspike-interval variability and firing irregularity in response to sustained depolarization. We conclude that Nav1.6 channels at axon initial segments contribute to persistent Na+ current and ensure a high degree of temporal precision in repetitive firing of CG cells. PMID:20173079

Spitzer Space Telescope IRS Spectral Mapping of Photoionized Columns in M16 and the Carina HII Regions

NASA Astrophysics Data System (ADS)

Cotera, Angela; Simpson, J. P.; Sellgren, K.; Stolovy, S. R.

2013-01-01

Photoevaporated columns of dust and gas - also called elephant trunks, pillars or fingers - are found in the periphery of many H II regions. They have been observed within the Galaxy, the SMC and the LMC. These features are thought to be sites of current star formation, but the question remains whether the columns persist because stars formed in the denser regions prior to interactions with the UV radiation and stellar winds of nearby massive stars, or because of core collapse resulting from these interactions. We have obtained Spitzer IRS spectral maps of three columns within M 16 and three columns within the Carina nebula, to test our understanding of the impact on these transitory features of differing stellar populations and initial conditions. We use the wealth of molecular, atomic and PAH emission lines located within the spectral range of the high resolution IRS modes (9.9-37.2 micron) to determine the excitation state, dust and gas temperatures, and probe the shock characteristics within the columns as a function of location. Using the IRS spectral mapping mode, in conjunction with the CUBISM tool and the CLOUDY H II region model code, we have constructed detailed maps of the accessible emission lines and derived parameters for each column. Mapping the distribution of the physical states of the dust and gas in these columns is enhancing our understanding of the competing processes within these dynamic objects. The data presented here represent the only IRS spectral maps of photoionized pillars.

Pain Intensity Moderates the Relationship Between Age and Pain Interference in Chronic Orofacial Pain Patients.

PubMed

Boggero, Ian A; Geiger, Paul J; Segerstrom, Suzanne C; Carlson, Charles R

2015-01-01

BACKGROUND/STUDY CONTEXT: Chronic pain is associated with increased interference in daily functioning that becomes more pronounced as pain intensity increases. Based on previous research showing that older adults maintain well-being in the face of pain as well as or better than their younger counterparts, the current study examined the interaction of age and pain intensity on interference in a sample of chronic orofacial pain patients. Data were obtained from the records of 508 chronic orofacial pain patients being seen for an initial evaluation from 2008 to 2012. Collected data included age (range: 18-78) and self-reported measures of pain intensity and pain interference. Bivariate correlations and regression models were used to assess for statistical interactions. Regression analyses revealed that pain intensity positively predicted pain interference (R(2) = .35, B = 10.40, SE = 0.62, t(507) = 16.70, p < .001). A significant interaction supported the primary hypothesis that aging was associated with reduced interference at high levels of pain intensity (ΔR(2) = .01, B = -1.31, SE = 0.63, t(505) = -2.90, p = .04). At high levels of pain intensity, interference decreased with age, although the age by pain intensity interaction effect was small. This evidence converges with aging theories, including socioemotional selectivity theory, which posits that as people age, they become more motivated to maximize positive emotions and minimize negative ones. The results highlight the importance of studying the mechanisms older adults use to successfully cope with pain.

Acute Bouts of Exercising Improved Mood, Rumination and Social Interaction in Inpatients With Mental Disorders.

PubMed

Brand, Serge; Colledge, Flora; Ludyga, Sebastian; Emmenegger, Raphael; Kalak, Nadeem; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Pühse, Uwe; Gerber, Markus

2018-01-01

Background: Studies at the macro level (such as longer-term interventions) showed that physical activity impacts positively on cognitive-emotional processes of patients with mental disorders. However, research focusing on the immediate impact of acute bouts of exercise (micro level) are missing. The aim of the present study was therefore to investigate whether and to what extent single bouts of moderately intense exercise can influence dimensions of psychological functioning in inpatients with mental disorders. Method: 129 inpatients (mean age: 38.16 years; 50.4% females) took part and completed a questionnaire both immediately before and immediately after exercising. Thirty inpatients completed the questionnaires a second time in the same week. The questionnaire covered socio-demographic and illness-related information. Further, the questionnaire asked about current psychological states such as mood, rumination, social interactions, and attention, tiredness, and physical strengths as a proxy of physiological states. Results: Psychological states improved from pre- to post-session. Improvements were observed for mood, social interactions, attention, and physical strengths. Likewise, rumination and tiredness decreased. Mood, rumination, and tiredness further improved, when patients completed the questionnaires the second time in the same week. Conclusion: At micro level, single bouts of exercise impacted positively on cognitive-emotional processes such as mood, rumination, attention and social interactions, and physiological states of tiredness and physical strengths among inpatients with mental disorders. In addition, further improvements were observed, if patients participated in physical activities a second time.

Acute Bouts of Exercising Improved Mood, Rumination and Social Interaction in Inpatients With Mental Disorders

PubMed Central

Brand, Serge; Colledge, Flora; Ludyga, Sebastian; Emmenegger, Raphael; Kalak, Nadeem; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Pühse, Uwe; Gerber, Markus

2018-01-01

Background: Studies at the macro level (such as longer-term interventions) showed that physical activity impacts positively on cognitive-emotional processes of patients with mental disorders. However, research focusing on the immediate impact of acute bouts of exercise (micro level) are missing. The aim of the present study was therefore to investigate whether and to what extent single bouts of moderately intense exercise can influence dimensions of psychological functioning in inpatients with mental disorders. Method: 129 inpatients (mean age: 38.16 years; 50.4% females) took part and completed a questionnaire both immediately before and immediately after exercising. Thirty inpatients completed the questionnaires a second time in the same week. The questionnaire covered socio-demographic and illness-related information. Further, the questionnaire asked about current psychological states such as mood, rumination, social interactions, and attention, tiredness, and physical strengths as a proxy of physiological states. Results: Psychological states improved from pre- to post-session. Improvements were observed for mood, social interactions, attention, and physical strengths. Likewise, rumination and tiredness decreased. Mood, rumination, and tiredness further improved, when patients completed the questionnaires the second time in the same week. Conclusion: At micro level, single bouts of exercise impacted positively on cognitive-emotional processes such as mood, rumination, attention and social interactions, and physiological states of tiredness and physical strengths among inpatients with mental disorders. In addition, further improvements were observed, if patients participated in physical activities a second time. PMID:29593592

20 CFR 216.16 - What is regular non-railroad employment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false What is regular non-railroad employment. 216.16 Section 216.16 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT ELIGIBILITY FOR AN ANNUITY Current Connection With the Railroad Industry § 216.16 What is...

Predissociation of oxygen in the B3Sigma(u)(-) state

NASA Technical Reports Server (NTRS)

Chiu, S. S.-L.; Cheung, A. S.-C.; Finch, M.; Jamieson, M. J.; Yoshino, K.; Dalgarno, A.; Parkinson, W. H.

1992-01-01

The predissociation linewidths and level shifts of vibrational levels of three oxygen isotopic molecules (O2)-16, (O-16)(O-18), and (O2)-18 arising from the interactions of the B3Sigma(u)(-) state with the four repulsive states 5Pi(u), 3Sigma(u)(+), 3Pi(u), and 1Pi(u) have been calculated. A set of parameters characterizing these interactions has been determined. Good agreement between calculated and experimental predissociation widths and shifts has been obtained for all the three isotopic molecules.

38 CFR 16.102 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Drug requirements administered by the Food and Drug Administration). It does not include research... student) conducting research obtains (1) Data through intervention or interaction with the individual, or... that are performed for research purposes. Interaction includes communication or interpersonal contact...

38 CFR 16.102 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Drug requirements administered by the Food and Drug Administration). It does not include research... student) conducting research obtains (1) Data through intervention or interaction with the individual, or... that are performed for research purposes. Interaction includes communication or interpersonal contact...

About increase of the large transvere momentum processes fraction in hA interactions at energies 5.10(14) - 10(16) eV according to the data on E.A.S. hadrons

NASA Technical Reports Server (NTRS)

Danilova, T. V.; Dubovy, A. G.; Erlykin, A. D.; Nesterova, N. M.; Chubenko, A. P.

1985-01-01

The lateral distributions of extensive air showers (EAS) hadrons obtained at Tien-Shan array are compared with the simulations. The simulation data have been treated in the same way as experimental data, including the recording method. The comparison shows that the experimental hadron lateral distributions are wider than simulated ones. On the base of this result the conclusion is drawn that the fraction of processes with large p (perpendicular) increases in hadron-air interactions at energies 5 x 10 to the 14 to 10 to the 16 eV compared with accelerator data in p-p interactions at lower energies.

Auxiliary field diffusion Monte Carlo calculations of light and medium-mass nuclei with local chiral interactions

NASA Astrophysics Data System (ADS)

Lonardoni, D.; Gandolfi, S.; Lynn, J. E.; Petrie, C.; Carlson, J.; Schmidt, K. E.; Schwenk, A.

2018-04-01

Quantum Monte Carlo methods have recently been employed to study properties of nuclei and infinite matter using local chiral effective-field-theory interactions. In this work, we present a detailed description of the auxiliary field diffusion Monte Carlo algorithm for nuclei in combination with local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We show results for the binding energy, charge radius, charge form factor, and Coulomb sum rule in nuclei with 3 ≤A ≤16 . Particular attention is devoted to the effect of different operator structures in the three-body force for different cutoffs. The outcomes suggest that local chiral interactions fit to few-body observables give a very good description of the ground-state properties of nuclei up to 16O, with the exception of one fit for the softer cutoff which predicts overbinding in larger nuclei.

Evidence for a role of SNX16 in regulating traffic between the early and later endosomal compartments.

PubMed

Hanson, Brendon J; Hong, Wanjin

2003-09-05

Sorting nexins (SNXs) are a growing family of proteins characterized by the presence of a PX domain. The PX domain mediates membrane association by interaction with phosphoinositides. The SNXs are generally believed to participate in membrane trafficking, but information regarding the function of individual proteins is limited. In this report, we describe the major characteristics of one member, SNX16. SNX16 is a novel 343-amino acid protein consisting of a central PX domain followed by a potential coiled-coil domain and a C-terminal region. Like other sorting nexins, SNX16 associates with the membrane via the PX domain which interacts with the phospholipid phosphatidylinositol 3-phosphate. We show via biochemical and cellular studies that SNX16 is distributed in both early and late endosome/lysosome structures. The coiled-coil domain is necessary for localization to the later endosomal structures, as mutant SNX16 lacking this domain was found only in early endosomes. Trafficking of internalized epidermal growth factor was also delayed by this SNX16 mutant, as these cells showed a delay in the segregation of epidermal growth factor in the early endosome for its delivery to later compartments. In addition, the coiled-coil domain is shown here to be important for homo-oligomerization of SNX16. Taken together, these results suggest that SNX16 is a sorting nexin that may function in the trafficking of proteins between the early and late endosomal compartments.

Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP.

PubMed

Kanack, Adam J; Newsom, Oliver J; Scaglione, Kenneth Matthew

2018-02-23

The accumulation of misfolded proteins promotes protein aggregation and neuronal death in many neurodegenerative diseases. To counteract misfolded protein accumulation, neurons have pathways that recognize and refold or degrade aggregation-prone proteins. One U-box-containing E3 ligase, C terminus of Hsc70-interacting protein (CHIP), plays a key role in this process, targeting misfolded proteins for proteasomal degradation. CHIP plays a protective role in mouse models of neurodegenerative disease, and in humans, mutations in CHIP cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16), a fatal neurodegenerative disease characterized by truncal and limb ataxia that results in gait instability. Here, we systematically analyzed CHIP mutations that cause SCAR16 and found that most SCAR16 mutations destabilize CHIP. This destabilization caused mutation-specific defects in CHIP activity, including increased formation of soluble oligomers, decreased interactions with chaperones, diminished substrate ubiquitination, and reduced steady-state levels in cells. Consistent with decreased CHIP stability promoting its dysfunction in SCAR16, most mutant proteins recovered activity when the assays were performed below the mutants' melting temperature. Together, our results have uncovered the molecular basis of genetic defects in CHIP function that cause SCAR16. Our insights suggest that compounds that improve the thermostability of genetic CHIP variants may be beneficial for treating patients with SCAR16. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed Central

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

2013-01-01

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

Listeria monocytogenes infection enhances the interaction between rat non-classical MHC-Ib molecule and Ly49 receptors.

PubMed

Shegarfi, Hamid; Kane, Kevin P; Nestvold, Janne

2018-05-01

Murine NK cell Ly49 receptors, functionally analogous to KIRs in humans recognize MHC class I molecules and play a key role in controlling NK cell function. We have previously shown that the paired activating Ly49s4 and inhibitory Ly49i4 receptors recognize undefined non-classical MHC-Ib ligands from the RT1-CE region in rats. Here, the RT1-CE16 gene of the RT1 d haplotype was stably transfected into the mouse RAW macrophage cell line, termed RAW-CE16 d cells. Combining RAW-CE16 d cells with Ly49 expressing reporter cells demonstrated Ly49i4 and Ly49s4 specificity for CE16 d . The Ly49s4/i4:CE16 d interaction was confirmed by specific MHC-I blocking monoclonal Abs. Further, we used our in vitro model to study the effect of Listeria monocytogenes (LM) on CE16 d after infection. LM infection and IFN-γ stimulation both led to enhanced CE16 d expression on the surface of transfected RAW-CE16 d cells. Interestingly, the reporter cells displayed increased response to LM-infected RAW-CE16 d cells compared with IFN-γ-treated RAW-CE16 d cells, suggesting a fundamental difference between these stimuli in supporting enhanced Ly49 recognition of CE16 d . Collectively, our data show that Ly49s4 and Ly49i4 recognize the non-classical RT1-CE16 d molecule, which in turn is up-regulated during LM infection and thereby may contribute to NK-mediated responses against infected cells.

Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus.

PubMed

Carossino, Mariano; Dini, Pouya; Kalbfleisch, Theodore S; Loynachan, Alan T; Canisso, Igor F; Shuck, Kathleen M; Timoney, Peter J; Cook, R Frank; Balasuriya, Udeni B R

2018-05-01

Equine arteritis virus (EAV) can establish long-term persistent infection in the reproductive tract of stallions and is shed in the semen. Previous studies showed that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and that persistent infection is maintained despite the presence of a local inflammatory and humoral and mucosal antibody responses. In this study, we demonstrated that equine seminal exosomes (SEs) are enriched in a small subset of microRNAs (miRNAs). Most importantly, we demonstrated that long-term EAV persistence is associated with the downregulation of an SE-associated miRNA (eca-mir-128) and with an enhanced expression of CXCL16 in the reproductive tract, a putative target of eca-mir-128. The findings presented here suggest that SE eca-mir-128 is implicated in the regulation of the CXCL16/CXCR6 axis in the reproductive tract of persistently infected stallions, a chemokine axis strongly implicated in EAV persistence. This is a novel finding and warrants further investigation to identify its specific mechanism in modulating the CXCL16/CXCR6 axis in the reproductive tract of the EAV long-term carrier stallion. IMPORTANCE Equine arteritis virus (EAV) has the ability to establish long-term persistent infection in the stallion reproductive tract and to be shed in semen, which jeopardizes its worldwide control. Currently, the molecular mechanisms of viral persistence are being unraveled, and these are essential for the development of effective therapeutics to eliminate persistent infection. Recently, it has been determined that long-term persistence is associated with a specific allele of the CXCL16 gene ( CXCL16S ) and is maintained despite induction of local inflammatory, humoral, and mucosal antibody responses. This study demonstrated that long-term persistence is associated with the downregulation of seminal exosome miRNA eca-mir-128 and enhanced expression of its putative target, CXCL16, in the reproductive tract. For the first time, this study suggests complex interactions between eca-mir-128 and cellular elements at the site of EAV persistence and implicates this miRNA in the regulation of the CXCL16/CXCR6 axis in the reproductive tract during long-term persistence. Copyright © 2018 American Society for Microbiology.

Ror2-Src signaling in metastasis of mouse melanoma cells is inhibited by NRAGE.

PubMed

Lai, Shan-Shan; Xue, Bin; Yang, Yang; Zhao, Li; Chu, Chao-Shun; Hao, Jia-Yin; Wen, Chuan-Jun

2012-11-01

The receptor tyrosine kinase (RTK) Ror2 plays important roles in developmental morphogenesis and mediates the filopodia formation in Wnt5a-induced cell migration. However, the function of Ror2 in noncanonical Wnt signaling resulting in cancer metastasis is largely unknown. Here, we show that Ror2 expression is higher in the highly metastatic murine B16-BL6 melanoma cells than in the low metastatic variant B16 cells. Overexpression of Ror2 increases the metastasis ability of B16 cells, and knockdown of Ror2 reduces the migration ability of B16-BL6 cells. Furthermore, the inhibition of Src kinase activity is critical for the Ror2-mediated cell migration upon Wnt5a treatment. The C-terminus of Ror2, which is deleted in brachydactyly type B (BDB), is essential for the mutual interaction with the SH1 domain of Src. Intriguingly, the Neurotrophin receptor-interacting MAGE homologue (NRAGE), which, as we previously reported, can remodel the cellular skeleton and inhibit cell-cell adhesion and metastasis of melanoma and pancreatic cancer, sharply blocks the interaction between Src and Ror2 and inhibits Ror2-mediated B16 cell migration by decreasing the activity of Src and focal adhesion kinase (FAK). Our data show that Ror2 is a potential factor in the tumorigenesis and metastasis in a Src-dependent manner that is negatively regulated by NRAGE. Copyright © 2012. Published by Elsevier Inc.

Magneto-optical observation of twisted vortices in type-II superconductors

NASA Astrophysics Data System (ADS)

Indenbom, M. V.; van der Beek, C. J.; Berseth, V.; Benoit, W.; D'Anna, G.; Erb, A.; Walker, E.; Flükiger, R.

1997-02-01

When magnetic flux penetrates a type-II superconductor, it does so as quantized flux lines or vortex lines, so called because each is surrounded by a supercurrent vortex. Interactions between such vortices lead to a very rich and well characterized phenomenology for this 'mixed state'. But an outstanding question remains: are individual vortex lines 'strong', or can they easily be cut and made to pass through one another? The concept of vortex cutting was originally proposed to account for dissipation observed in superconducting wires oriented parallel to an applied magnetic field, where the vortex lines and transport current should be in a force-free configuration1-6. Previous experiments, however, have been unable to establish the vortex topology in the force-free configuration or the size of the energy barrier for vortex cutting. Here we report magneto-optical images of YBa2Cu3O7-δ samples in the force-free configuration which show that thousands of vortex lines can twist together to form highly stable structures. In some cases, these 'vortex twisters' interact with one another to produce wave-like dynamics. Our measurements also determine directly the current required to initiate vortex cutting, and show that it is much higher than that needed to overcome the pinning of vortices by material defects. This implies that thermodynamic phases of entangled vortices7-10 are intrinsically stable and may occupy a significant portion of the mixed-state phase diagram for type-II superconductors.

A Biodesigned Nanocomposite Biomaterial for Auricular Cartilage Reconstruction.

PubMed

Nayyer, Leila; Jell, Gavin; Esmaeili, Ali; Birchall, Martin; Seifalian, Alexander M

2016-05-01

Current biomaterials for auricular replacement are associated with high rates of infection and extrusion. The development of new auricular biomaterials that mimic the mechanical properties of native tissue and promote desirable cellular interactions may prevent implant failure. A porous 3D nanocomposite scaffold (NS) based on POSS-PCU (polyhedral oligomeric silsesquioxane nanocage into polycarbonate based urea-urethane) is developed with an elastic modulus similar to native ear. In vitro biological interactions on this NS reveal greater protein adsorption, increased fibroblast adhesion, proliferation, and collagen production compared with Medpor (the current synthetic auricular implant). In vivo, the POSS-PCU with larger pores (NS2; 150-250 μm) have greater tissue ingrowth (≈5.8× and ≈1.4 × increase) than the POSS-PCU with smaller pores (NS1; 100-50 μm) and when compared to Medpor (>100 μm). The NS2 with the larger pores demonstrates a reduced fibrotic encapsulation compared with NS1 and Medpor (≈4.1× and ≈1.6×, respectively; P < 0.05). Porosity also influences the amount of neovascularization within the implants, with no blood vessel observed in NS1 (12 weeks postimplantation). The lack of chronic inflammatory response for all materials may indicate that the elastic modulus and pore size of the implant scaffold could be important design considerations for influencing fibrotic responses to auricular and other soft tissue implants. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mantle-lithosphere interaction beneath the Yellowstone-Snake River province

NASA Astrophysics Data System (ADS)

van Keken, P. E.; Lin, S.

2006-12-01

The Yellowstone-Snake River province (YSRP) is one the few currently active continental hotspot locations and the only one with a clear age progression from 16-17 Ma eruptions at the Oregon-Nevada border to the present day activity at in Western Wyoming. The province has a number of characteristics that are quite similar to oceanic hotspot regions, which include a topographic bulge and geoid anomaly. The initial silicic magmatism is contemporaneous with the Columbia River Basalts, but this would require significant northward transport of basalt from the hotspot track, which is potentially accommodated by lateral transport in the crust or by a sideways transport from more competent lithosphere to a weaker spot. We will present 3D models of plumes and plume heads interacting with the lithosphere for the YSRP following the approach of Lin et al. (2005). We are particularly interested in the role of the variable properties of the lithosphere and surface tectonics influence the magmatic emplacement. We investigate the type conditions under which we can generate the Columbia River Basalts as a part of a single Yellowstone plume rising below the western US. This provides important estimates of the original size of the plume head, the current buoyancy flux and the lateral transport of mantle below the lithosphere. S.C. Lin, B.Y. Kuo, L.Y. Chiao, P.E. van Keken, Thermal plume models and melt generation in East Africa: A dynamical modeling approach, Earth Planet. Sci. Lett., 237, 175-192, 2005.

Adolescents’ Perceptions Regarding Effective Tobacco Use Prevention Strategies for their Younger Counterparts: A Qualitative Study in Malaysia

PubMed Central

Zin, Faridah Mohd; Hillaluddin, Azlin Hilma; Mustaffa, Jamaludin

2016-01-01

Purpose: The present qualitative study explored adolescents’ perceptions regarding effective strategies to prevent adolescents from using tobacco products (TP). Apart from the commercial TPs, there has been emerging use of alternatives such as vapes, e-cigarettes and shisha. This unfortunate phenomenon continues despite the currently available preventive strategies. Thus, understanding of the perceptions of the current generation would be valuable to provide new insights. Methods: Purposive sampling was utilized to recruit 40 adolescents between the age of 15 and 16 years old attending public daily secondary schools. Eight focus group discussions were conducted among the TP users, ex-users and non-users. Data were analyzed using a thematic content analysis procedure with NVivo. Results: Among barriers with the currently available strategies were having teachers who smoke tobacco, addiction to nicotine and self-perceptions of being healthy. The content of any program should include knowledge on negative outcomes of using tobacco products and awareness of the legislation together with ways to overcome peer and family influence including improving self-efficacy and refusal skills. Strategies were suggested to be delivered using information technology which provides interactive learning and visual effects. Conclusions: Adolescents agreed that the content and delivery of tobacco use prevention strategies need to be revised to suit the current generation to ensure sustainability. PMID:28122443

Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses

PubMed Central

Iqbal, Jawed; Ansari, Mairaj Ahmed; Kumar, Binod; Dutta, Dipanjan; Roy, Arunava; Chikoti, Leela; Pisano, Gina; Dutta, Sujoy; Veettil, Mohanan Valiya; Chandran, Bala

2016-01-01

IFI16 (gamma-interferon-inducible protein 16), a predominantly nuclear protein involved in transcriptional regulation, also functions as an innate immune response DNA sensor and induces the IL-1β and antiviral type-1 interferon-β (IFN-β) cytokines. We have shown that IFI16, in association with BRCA1, functions as a sequence independent nuclear sensor of episomal dsDNA genomes of KSHV, EBV and HSV-1. Recognition of these herpesvirus genomes resulted in IFI16 acetylation, BRCA1-IFI16-ASC-procaspase-1 inflammasome formation, cytoplasmic translocation, and IL-1β generation. Acetylated IFI16 also interacted with cytoplasmic STING and induced IFN-β. However, the identity of IFI16 associated nuclear proteins involved in STING activation and the mechanism is not known. Mass spectrometry of proteins precipitated by anti-IFI16 antibodies from uninfected endothelial cell nuclear lysate revealed that histone H2B interacts with IFI16. Single and double proximity ligation microscopy, immunoprecipitation, EdU-genome labeled virus infection, and chromatin immunoprecipitation studies demonstrated that H2B is associated with IFI16 and BRCA1 in the nucleus in physiological conditions. De novo KSHV and HSV-1 infection as well as latent KSHV and EBV infection induces the cytoplasmic distribution of H2B-IFI16, H2B-BRCA1 and IFI16-ASC complexes. Vaccinia virus (dsDNA) cytoplasmic replication didn’t induce the redistribution of nuclear H2B-IFI16 or H2B into the cytoplasm. H2B is critical in KSHV and HSV-1 genome recognition by IFI16 during de novo infection. Viral genome sensing by IFI16-H2B-BRCA1 leads to BRCA1 dependent recruitment of p300, and acetylation of H2B and IFI16. BRCA1 knockdown or inhibition of p300 abrogated the acetylation of H2B-IFI16 or H2B. Ran-GTP protein mediated the translocation of acetylated H2B and IFI16 to the cytoplasm along with BRCA1 that is independent of IFI16-ASC inflammasome. ASC knockdown didn’t affect the acetylation of H2B, its cytoplasmic transportation, and the association of STING with IFI16 and H2B during KSHV infection. Absence of H2B didn’t affect IFI16-ASC association and cytoplasmic distribution and thus demonstrating that IFI16-H2B complex is independent of IFI16-ASC-procaspase-1-inflammasome complex formed during infection. The H2B-IFI16-BRCA1 complex interacted with cGAS and STING in the cytoplasm leading to TBK1 and IRF3 phosphorylation, nuclear translocation of pIRF3 and IFN-β production. Silencing of H2B, cGAS and STING inhibited IFN-β induction but not IL-1β secretion, and cGAMP activity is significantly reduced by H2B and IFI16 knockdown during infection. Silencing of ASC inhibited IL-1β secretion but not IFN-β secretion during de novo KSHV and HSV-1 infection. These studies identify H2B as an innate nuclear sensor mediating a novel extra chromosomal function, and reveal that two IFI16 complexes mediate KSHV and HSV-1 genome recognition responses, with recognition by the IFI16-BRCA1-H2B complex resulting in IFN-β responses and recognition by IFI16-BRCA1 resulting in inflammasome responses. PMID:27764250

Ring current dynamics and plasma sheet sources. [magnetic storms

NASA Technical Reports Server (NTRS)

Lyons, L. R.

1984-01-01

The source of the energized plasma that forms in geomagnetic storm ring currents, and ring current decay are discussed. The dominant loss processes for ring current ions are identified as charge exchange and resonant interactions with ion-cyclotron waves. Ring current ions are not dominated by protons. At L4 and energies below a few tens of keV, O+ is the most abundant ion, He+ is second, and protons are third. The plasma sheet contributes directly or indirectly to the ring current particle population. An important source of plasma sheet ions is earthward streaming ions on the outer boundary of the plasma sheet. Ion interactions with the current across the geomagnetic tail can account for the formation of this boundary layer. Electron interactions with the current sheet are possibly an important source of plasma sheet electrons.

NFI-Ski interactions mediate transforming growth factor beta modulation of human papillomavirus type 16 early gene expression.

PubMed

Baldwin, Amy; Pirisi, Lucia; Creek, Kim E

2004-04-01

Human papillomaviruses (HPVs) are present in virtually all cervical cancers. An important step in the development of malignant disease, including cervical cancer, involves a loss of sensitivity to transforming growth factor beta (TGF-beta). HPV type 16 (HPV16) early gene expression, including that of the E6 and E7 oncoprotein genes, is under the control of the upstream regulatory region (URR), and E6 and E7 expression in HPV16-immortalized human epithelial cells is inhibited at the transcriptional level by TGF-beta. While the URR contains a myriad of transcription factor binding sites, including seven binding sites for nuclear factor I (NFI), the specific sequences within the URR or the transcription factors responsible for TGF-beta modulation of the URR remain unknown. To identify potential transcription factors and binding sites involved in TGF-beta modulation of the URR, we performed DNase I footprint analysis on the HPV16 URR using nuclear extracts from TGF-beta-sensitive HPV16-immortalized human keratinocytes (HKc/HPV16) treated with and without TGF-beta. Differentially protected regions were found to be located around NFI binding sites. Electrophoretic mobility shift assays, using the NFI binding sites as probes, showed decreased binding upon TGF-beta treatment. This decrease in binding was not due to reduced NFI protein or NFI mRNA levels. Mutational analysis of individual and multiple NFI binding sites in the URR defined their role in TGF-beta sensitivity of the promoter. Overexpression of the NFI family members in HKc/HPV16 decreased the ability of TGF-beta to inhibit the URR. Since the oncoprotein Ski has been shown to interact with and increase the transcriptional activity of NFI and since cellular Ski levels are decreased by TGF-beta treatment, we explored the possibility that Ski may provide a link between TGF-beta signaling and NFI activity. Anti-NFI antibodies coimmunoprecipitated endogenous Ski in nuclear extracts from HKc/HPV16, confirming that NFI and Ski interact in these cells. Ski levels dramatically decreased upon TGF-beta treatment of HKc/HPV16, and overexpression of Ski eliminated the ability of TGF-beta to inhibit the URR. Based on these studies, we propose that TGF-beta inhibition of HPV16 early gene expression is mediated by a decrease in Ski levels, which in turn dramatically reduces NFI activity.

Critical Ethical Issues in Online Counseling: Assessing Current Practices with an Ethical Intent Checklist

ERIC Educational Resources Information Center

Shaw, Holly E.; Shaw, Sarah F.

2006-01-01

The authors used a 16-item Ethical Intent Checklist, developed from the American Counseling Association's (1999) Ethical Standards for Internet Online Counseling, to assess the current practices of 88 online counseling Web sites. Results showed fewer than half of online counselors were following the accepted practice on 8 of the 16 items. Online…

Ultraviolet Light Curves of Gaia16apd in Superluminous Supernova Models

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

Tolstov, Alexey; Zhiglo, Andrey; Nomoto, Ken’ichi

2017-08-10

Observations of Gaia16apd revealed extremely luminous ultraviolet emission among superluminous supernovae (SLSNe). Using radiation hydrodynamics simulations, we perform a comparison of UV light curves, color temperatures, and photospheric velocities between the most popular SLSN models: pair-instability supernova, magnetar, and interaction with circumstellar medium. We find that the interaction model is the most promising to explain the extreme UV luminosity of Gaia16apd. The differences in late-time UV emission and in color evolution found between the models can be used to link an observed SLSN event to the most appropriate model. Observations at UV wavelengths can be used to clarify the naturemore » of SLSNe and more attention should be paid to them in future follow-up observations.« less

Postdivorce living arrangements, parent conflict, and long-term physical health correlates for children of divorce.

PubMed

Fabricius, William V; Luecken, Linda J

2007-06-01

The authors tested a biopsychosocial model in which young adults' long-term relationships with fathers and ongoing distress surrounding their parents' divorces mediated the relationship between disrupted parenting (i.e., exposure to parent conflict before the divorce and up to 5 years after, and amount of time with father postdivorce) and indicators of their physical health. University students whose parents divorced before they were 16 (n = 266) participated. Findings supported the model. The more time children lived with their fathers after divorce, the better their current relationships were with their fathers, independent of parent conflict. The more parent conflict they experienced, the worse their relationships were with their fathers and the more distress they currently felt about their parents' divorce, independent of time with father. Poor father-child relationships and more distress in turn predicted poorer health status. There was no interaction between exposure to parent conflict and time with father; thus, more time with father was beneficial in both high- and low-conflict families, and more exposure to parent conflict was detrimental at both high and low levels of time with father.

Optimization of Acid Black 172 decolorization by electrocoagulation using response surface methodology

PubMed Central

2012-01-01

This paper utilizes a statistical approach, the response surface optimization methodology, to determine the optimum conditions for the Acid Black 172 dye removal efficiency from aqueous solution by electrocoagulation. The experimental parameters investigated were initial pH: 4–10; initial dye concentration: 0–600 mg/L; applied current: 0.5-3.5 A and reaction time: 3–15 min. These parameters were changed at five levels according to the central composite design to evaluate their effects on decolorization through analysis of variance. High R2 value of 94.48% shows a high correlation between the experimental and predicted values and expresses that the second-order regression model is acceptable for Acid Black 172 dye removal efficiency. It was also found that some interactions and squares influenced the electrocoagulation performance as well as the selected parameters. Optimum dye removal efficiency of 90.4% was observed experimentally at initial pH of 7, initial dye concentration of 300 mg/L, applied current of 2 A and reaction time of 9.16 min, which is close to model predicted (90%) result. PMID:23369574

Practices for Social Interaction in the Language-Learning Classroom: Disengagements from Dyadic Task Interaction

ERIC Educational Resources Information Center

Hellermann, John; Cole, Elizabeth

2009-01-01

Using conversation analysis and situated learning theory, in this paper we analyze the peer dyadic interactions of one adult learner of English in class periods 16 months apart. The analyses in the paper present microgenetic and longitudinal perspectives on the learner's increasing participation in his classroom communities of practice. The focus…

Differences in Perceived Implementation of a Standard versus Peer-Led Interactive Substance Abuse Prevention Program

ERIC Educational Resources Information Center

Valente, Thomas W.; Okamoto, Janet; Pumpuang, Patchareeya; Okamoto, Paula; Sussman, Steve

2007-01-01

Objective: To assess perceived implementation of 2 substance-abuse prevention programs: a standard one and a peer-led interactive one. Methods: Data from 16 health educators were collected after 504 classroom sessions, 63 of which were observed by 24 monitors. Results: In the interactive program, health educators (HEs) followed the curriculum less…

p16 gene silencing along with p53 single-nucleotide polymorphism and risk of esophageal cancer in Northeast India.

PubMed

Das, Mandakini; Sharma, Santanu Kumar; Sekhon, Gaganpreet Singh; Mahanta, Jagadish; Phukan, Rup Kumar; Jalan, Bimal Kumar

2017-05-01

The high incidence of esophageal cancer in Northeast India and the unique ethnic background and dietary habits provide a great opportunity to study the molecular genetics behind esophageal squamous cell carcinoma in this part of the region. We hypothesized that in addition to currently known environmental risk factors for esophageal cancer, genetic and epigenetic factors are also involved in esophageal carcinogenesis in Northeast India. Therefore, in this study, we explored the possible association between the two important G1 cell cycle regulatory genes p16 and p53 and environmental risk factors and risk of esophageal carcinogenesis. A total of 100 newly diagnosed esophageal cancer cases along with equal number of age-, sex-, and ethnicity-matched controls were included in this study. Methylation-specific polymerase chain reaction was used to determine the p16 promoter methylation status. Single-nucleotide polymorphism at codon 72 of p53 gene was assessed by the polymerase chain reaction-restriction fragment length polymorphism method. Aberrant methylation of p16 gene was seen in 81% of esophageal cancer cases. Hypermethylation of p16 gene was not found in healthy controls. p53 Pro/Pro genotype was found to be a risk genotype in Northeast India compared with Arg/Pro and Arg/Arg. p53 variant/polymorphism was significantly associated with esophageal cancer risk in the study population under all three genetic models, namely, dominant model (Arg/Pro + Pro/Pro vs Arg/Arg odds ratio = 2.25, confidence interval = 1.19-4.26; p = 0.012), recessive model (Arg/Arg + Arg/Pro vs Pro/Pro odds ratio = 2.35, confidence interval = 1.24-4.44; p = 0.008), and homozygous model (Pro/Pro vs Arg/Arg odds ratio = 3.33, confidence interval = 1.54-7.20; p = 0.002). However, p53 variant/polymorphism was not statistically associated with esophageal cancer risk under the heterozygous model (Pro/Pro vs Arg/Pro). In the case-only analysis based on p16 methylation, the p53 variant/polymorphism (Pro/Pro or Arg/Pro) showed significant association for esophageal cancer risk (odds ratio = 3.33, confidence interval = 1.54-7.20; p = 0.002). Gene-gene and gene-environment interaction using the case-only approach revealed a strong association between p16 methylation, p53 single-nucleotide polymorphism, and environmental factors and esophageal cancer risk. Cases with p16 methylation and p53 variant/polymorphism (Pro/Pro or Arg/Pro) along with both betel quid and tobacco chewing habit (odds ratio = 8.29, confidence interval = 1.14-60.23; p = 0.037) conferred eightfold increased risk toward esophageal cancer development. This study reveals a synergistic interaction between epigenetic, genetic, and environmental factors and risk of esophageal cancer in this high-incidence region of Northeast India. The inactivation of either p16 or p53 in a majority of esophageal cancer cases in this study suggests the possible crosstalk between the important cell cycle genes.

GENETIC INTERACTIONS BETWEEN ADRB2 AND PTGER4 ON RESPONSES TO SALMETEROL OR MONTELUKAST IN JAPANESE PATIENTS WITH MILD PERSISTENT ASTHMA.

PubMed

Yamada, Hideyasu; Masuko, Hironori; Inui, Toshihide; Kanazawa, Jun; Yatagai, Yohei; Sakamoto, Tohru; Iijima, Hiroaki; Konno, Satoshi; Shimizu, Kaoruko; Makita, Hironi; Nishimura, Masaharu; Kokubu, Fumio; Saito, Takefumi; Endo, Takeo; Ninomiya, Hiroki; Kaneko, Norihiro; Hizawa, Nobuyuki

2016-01-01

Long-acting β 2 -agonists (LABA) and leukotriene receptor antagonists (LTRA) are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. In our previous study, the Gly16Arg genotype of the β 2 -adrenergic receptor (ADRB2) gene did not influence the differential bronchodilator effect of salmeterol versus montelukast as an add-on therapy to ICS within 16 weeks of follow-up (the J-Blossom study). We examined if genes encoding CYSLTR1, CYSLTR2, PTGER2 or PTGER4 could explain differential responses to salmeterol versus montelukast using the participants of the J-Blossom study. This study included 76 patients with mild-to-moderate asthma. The difference in peak expiratory flow (PEF) (ΔPEF, l/min) after 16 weeks of treatment with salmeterol (ΔPEFsal) versus montelukast (ΔPEFmon) was associated with the genotypes at each of 4 genes. In addition, multivariate analyses were used to identify a gene-gene interaction between ADRB2 gene and each of these 4 genes. Although none of 4 genes were associated with ΔPEFsal-ΔPEFmon in the univariate analyses, multivariate analysis showed that PTGER4 gene, interacting with ADRB2 Gly16Arg, was associated with ΔPEFsal-ΔPEFmon (p=0.0032). Our findings suggested that the interactions between two genetic loci at ADRB2 and PTGER4 is important in determining the differential response to salmeterol versus montelukast in patients with chronic adult asthma.

Dark matter search in a Beam-Dump eXperiment (BDX) at Jefferson Lab: an update on PR12-16-001

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

Battaglieri, M.

This document is an update to the proposal PR12-16-001 Dark matter search in a Beam-Dump eXperiment (BDX) at Jefferson Lab submitted to JLab-PAC44 in 2016 reporting progress in addressing questions raised regarding the beam-on backgrounds. The concerns are addressed by adopting a new simulation tool, FLUKA, and planning measurements of muon fluxes from the dump with its existing shielding around the dump. First, we have implemented the detailed BDX experimental geometry into a FLUKA simulation, in consultation with experts from the JLab Radiation Control Group. The FLUKA simulation has been compared directly to our GEANT4 simulations and shown to agreemore » in regions of validity. The FLUKA interaction package, with a tuned set of biasing weights, is naturally able to generate reliable particle distributions with very small probabilities and therefore predict rates at the detector location beyond the planned shielding around the beam dump. Second, we have developed a plan to conduct measurements of the muon ux from the Hall-A dump in its current configuration to validate our simulations.« less

Molecular docking and inhibition kinetics of α-glucosidase activity by labdane diterpenes isolated from tora seeds (Alpinia nigra B.L. Burtt.).

PubMed

Ghosh, Sudipta; Rangan, Latha

2015-02-01

Current approach against type 2 diabetes involves α-glucosidase inhibitors like acarbose associated with many side effects. Therefore, as an alternative to the existing drug, many natural products mainly from plant sources have been investigated which inhibit α-glucosidase. Here, we have selected medicinally important Alpinia nigra to explore its α-glucosidase inhibitory activity. Organic extracts of seeds and two purified natural diterpenes I: (E)-labda-8(17), 12-diene-15, 16-dial and II: (E)-8β, 17-epoxylabd-12-ene-15, 16-dial from A. nigra were investigated towards inhibition of α-glucosidase activity. Dose-dependent inhibition pattern were observed for seed extracts and both the compounds. Further, inhibition kinetics studies of the diterpenes indicated a non-competitive type of inhibition against α-glucosidase. Docking studies were carried out which revealed that both the diterpenes interacted within the active site of N-terminal and C-terminal domain of human maltase-glucoamylase enzyme, respectively. This is the first report of α-glucosidase inhibitory activity of these isolated diterpenes and their higher inhibitory potential than any terpenoids studied till date against α-glucosidase.

Modification on ursodeoxycholic acid (UDCA) scaffold. discovery of bile acid derivatives as selective agonists of cell-surface G-protein coupled bile acid receptor 1 (GP-BAR1).

PubMed

Sepe, Valentina; Renga, Barbara; Festa, Carmen; D'Amore, Claudio; Masullo, Dario; Cipriani, Sabrina; Di Leva, Francesco Saverio; Monti, Maria Chiara; Novellino, Ettore; Limongelli, Vittorio; Zampella, Angela; Fiorucci, Stefano

2014-09-25

Bile acids are signaling molecules interacting with the nuclear receptor FXR and the G-protein coupled receptor 1 (GP-BAR1/TGR5). GP-BAR1 is a promising pharmacological target for the treatment of steatohepatitis, type 2 diabetes, and obesity. Endogenous bile acids and currently available semisynthetic bile acids are poorly selective toward GP-BAR1 and FXR. Thus, in the present study we have investigated around the structure of UDCA, a clinically used bile acid devoid of FXR agonist activity, to develop a large family of side chain modified 3α,7β-dihydroxyl cholanoids that selectively activate GP-BAR1. In vivo and in vitro pharmacological evaluation demonstrated that administration of compound 16 selectively increases the expression of pro-glucagon 1, a GP-BAR1 target, in the small intestine, while it had no effect on FXR target genes in the liver. Further, compound 16 results in a significant reshaping of bile acid pool in a rodent model of cholestasis. These data demonstrate that UDCA is a useful scaffold to generate novel and selective steroidal ligands for GP-BAR1.

Swept shock/boundary layer interaction experiments in support of CFD code validation

NASA Technical Reports Server (NTRS)

Settles, G. S.; Lee, Y.

1990-01-01

Research on the topic of shock wave/turbulent boundary layer interaction was carried out. Skin friction and surface pressure measurements in fin-induced, swept interactions were conducted, and heat transfer measurements in the same flows are planned. The skin friction data for a strong interaction case (Mach 4, fin-angles equal 16 and 20 degrees) were obtained, and their comparison with computational results was published. Surface pressure data for weak-to-strong fin interactions were also obtained.

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2010-07-01

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Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.

PubMed

Webster, Chris R; Mahaffy, Paul R; Flesch, Gregory J; Niles, Paul B; Jones, John H; Leshin, Laurie A; Atreya, Sushil K; Stern, Jennifer C; Christensen, Lance E; Owen, Tobias; Franz, Heather; Pepin, Robert O; Steele, Andrew; Achilles, Cherie; Agard, Christophe; Alves Verdasca, José Alexandre; Anderson, Robert; Anderson, Ryan; Archer, Doug; Armiens-Aparicio, Carlos; Arvidson, Ray; Atlaskin, Evgeny; Aubrey, Andrew; Baker, Burt; Baker, Michael; Balic-Zunic, Tonci; Baratoux, David; Baroukh, Julien; Barraclough, Bruce; Bean, Keri; Beegle, Luther; Behar, Alberto; Bell, James; Bender, Steve; Benna, Mehdi; Bentz, Jennifer; Berger, Gilles; Berger, Jeff; Berman, Daniel; Bish, David; Blake, David F; Blanco Avalos, Juan J; Blaney, Diana; Blank, Jen; Blau, Hannah; Bleacher, Lora; Boehm, Eckart; Botta, Oliver; Böttcher, Stephan; Boucher, Thomas; Bower, Hannah; Boyd, Nick; Boynton, Bill; Breves, Elly; Bridges, John; Bridges, Nathan; Brinckerhoff, William; Brinza, David; Bristow, Thomas; Brunet, Claude; Brunner, Anna; Brunner, Will; Buch, Arnaud; Bullock, Mark; Burmeister, Sönke; Cabane, Michel; Calef, Fred; Cameron, James; Campbell, John; Cantor, Bruce; Caplinger, Michael; Caride Rodríguez, Javier; Carmosino, Marco; Carrasco Blázquez, Isaías; Charpentier, Antoine; Chipera, Steve; Choi, David; Clark, Benton; Clegg, Sam; Cleghorn, Timothy; Cloutis, Ed; Cody, George; Coll, Patrice; Conrad, Pamela; Coscia, David; Cousin, Agnès; Cremers, David; Crisp, Joy; Cros, Alain; Cucinotta, Frank; d'Uston, Claude; Davis, Scott; Day, Mackenzie; de la Torre Juarez, Manuel; DeFlores, Lauren; DeLapp, Dorothea; DeMarines, Julia; DesMarais, David; Dietrich, William; Dingler, Robert; Donny, Christophe; Downs, Bob; Drake, Darrell; Dromart, Gilles; Dupont, Audrey; Duston, Brian; Dworkin, Jason; Dyar, M Darby; Edgar, Lauren; Edgett, Kenneth; Edwards, Christopher; Edwards, Laurence; Ehlmann, Bethany; Ehresmann, Bent; Eigenbrode, Jen; Elliott, Beverley; Elliott, Harvey; Ewing, Ryan; Fabre, Cécile; Fairén, Alberto; Farley, Ken; Farmer, Jack; Fassett, Caleb; Favot, Laurent; Fay, Donald; Fedosov, Fedor; Feldman, Jason; Feldman, Sabrina; Fisk, Marty; Fitzgibbon, Mike; Floyd, Melissa; Flückiger, Lorenzo; Forni, Olivier; Fraeman, Abby; Francis, Raymond; François, Pascaline; Freissinet, Caroline; French, Katherine Louise; Frydenvang, Jens; Gaboriaud, Alain; Gailhanou, Marc; Garvin, James; Gasnault, Olivier; Geffroy, Claude; Gellert, Ralf; Genzer, Maria; Glavin, Daniel; Godber, Austin; Goesmann, Fred; Goetz, Walter; Golovin, Dmitry; Gómez Gómez, Felipe; Gómez-Elvira, Javier; Gondet, Brigitte; Gordon, Suzanne; Gorevan, Stephen; Grant, John; Griffes, Jennifer; Grinspoon, David; Grotzinger, John; Guillemot, Philippe; Guo, Jingnan; Gupta, Sanjeev; Guzewich, Scott; Haberle, Robert; Halleaux, Douglas; Hallet, Bernard; Hamilton, Vicky; Hardgrove, Craig; Harker, David; Harpold, Daniel; Harri, Ari-Matti; Harshman, Karl; Hassler, Donald; Haukka, Harri; Hayes, Alex; Herkenhoff, Ken; Herrera, Paul; Hettrich, Sebastian; Heydari, Ezat; Hipkin, Victoria; Hoehler, Tori; Hollingsworth, Jeff; Hudgins, Judy; Huntress, Wesley; Hurowitz, Joel; Hviid, Stubbe; Iagnemma, Karl; Indyk, Steve; Israël, Guy; Jackson, Ryan; Jacob, Samantha; Jakosky, Bruce; Jensen, Elsa; Jensen, Jaqueline Kløvgaard; Johnson, Jeffrey; Johnson, Micah; Johnstone, Steve; Jones, Andrea; Joseph, Jonathan; Jun, Insoo; Kah, Linda; Kahanpää, Henrik; Kahre, Melinda; Karpushkina, Natalya; Kasprzak, Wayne; Kauhanen, Janne; Keely, Leslie; Kemppinen, Osku; Keymeulen, Didier; Kim, Myung-Hee; Kinch, Kjartan; King, Penny; Kirkland, Laurel; Kocurek, Gary; Koefoed, Asmus; Köhler, Jan; Kortmann, Onno; Kozyrev, Alexander; Krezoski, Jill; Krysak, Daniel; Kuzmin, Ruslan; Lacour, Jean Luc; Lafaille, Vivian; Langevin, Yves; Lanza, Nina; Lasue, Jeremie; Le Mouélic, Stéphane; Lee, Ella Mae; Lee, Qiu-Mei; Lees, David; Lefavor, Matthew; Lemmon, Mark; Lepinette Malvitte, Alain; Léveillé, Richard; Lewin-Carpintier, Éric; Lewis, Kevin; Li, Shuai; Lipkaman, Leslie; Little, Cynthia; Litvak, Maxim; Lorigny, Eric; Lugmair, Guenter; Lundberg, Angela; Lyness, Eric; Madsen, Morten; Maki, Justin; Malakhov, Alexey; Malespin, Charles; Malin, Michael; Mangold, Nicolas; Manhes, Gérard; Manning, Heidi; Marchand, Geneviève; Marín Jiménez, Mercedes; Martín García, César; Martin, Dave; Martin, Mildred; Martínez-Frías, Jesús; Martín-Soler, Javier; Martín-Torres, F Javier; Mauchien, Patrick; Maurice, Sylvestre; McAdam, Amy; McCartney, Elaina; McConnochie, Timothy; McCullough, Emily; McEwan, Ian; McKay, Christopher; McLennan, Scott; McNair, Sean; Melikechi, Noureddine; Meslin, Pierre-Yves; Meyer, Michael; Mezzacappa, Alissa; Miller, Hayden; Miller, Kristen; Milliken, Ralph; Ming, Douglas; Minitti, Michelle; Mischna, Michael; Mitrofanov, Igor; Moersch, Jeff; Mokrousov, Maxim; Molina Jurado, Antonio; Moores, John; Mora-Sotomayor, Luis; Morookian, John Michael; Morris, Richard; Morrison, Shaunna; Mueller-Mellin, Reinhold; Muller, Jan-Peter; Muñoz Caro, Guillermo; Nachon, Marion; Navarro López, Sara; Navarro-González, Rafael; Nealson, Kenneth; Nefian, Ara; Nelson, Tony; Newcombe, Megan; Newman, Claire; Newsom, Horton; Nikiforov, Sergey; Nixon, Brian; Noe Dobrea, Eldar; Nolan, Thomas; Oehler, Dorothy; Ollila, Ann; Olson, Timothy; de Pablo Hernández, Miguel Ángel; Paillet, Alexis; Pallier, Etienne; Palucis, Marisa; Parker, Timothy; Parot, Yann; Patel, Kiran; Paton, Mark; Paulsen, Gale; Pavlov, Alex; Pavri, Betina; Peinado-González, Verónica; Peret, Laurent; Perez, Rene; Perrett, Glynis; Peterson, Joe; Pilorget, Cedric; Pinet, Patrick; Pla-García, Jorge; Plante, Ianik; Poitrasson, Franck; Polkko, Jouni; Popa, Radu; Posiolova, Liliya; Posner, Arik; Pradler, Irina; Prats, Benito; Prokhorov, Vasily; Purdy, Sharon Wilson; Raaen, Eric; Radziemski, Leon; Rafkin, Scot; Ramos, Miguel; Rampe, Elizabeth; Raulin, François; Ravine, Michael; Reitz, Günther; Rennó, Nilton; Rice, Melissa; Richardson, Mark; Robert, François; Robertson, Kevin; Rodriguez Manfredi, José Antonio; Romeral-Planelló, Julio J; Rowland, Scott; Rubin, David; Saccoccio, Muriel; Salamon, Andrew; Sandoval, Jennifer; Sanin, Anton; Sans Fuentes, Sara Alejandra; Saper, Lee; Sarrazin, Philippe; Sautter, Violaine; Savijärvi, Hannu; Schieber, Juergen; Schmidt, Mariek; Schmidt, Walter; Scholes, Daniel; Schoppers, Marcel; Schröder, Susanne; Schwenzer, Susanne; Sebastian Martinez, Eduardo; Sengstacken, Aaron; Shterts, Ruslan; Siebach, Kirsten; Siili, Tero; Simmonds, Jeff; Sirven, Jean-Baptiste; Slavney, Susie; Sletten, Ronald; Smith, Michael; Sobrón Sánchez, Pablo; Spanovich, Nicole; Spray, John; Squyres, Steven; Stack, Katie; Stalport, Fabien; Stein, Thomas; Stewart, Noel; Stipp, Susan Louise Svane; Stoiber, Kevin; Stolper, Ed; Sucharski, Bob; Sullivan, Rob; Summons, Roger; Sumner, Dawn; Sun, Vivian; Supulver, Kimberley; Sutter, Brad; Szopa, Cyril; Tan, Florence; Tate, Christopher; Teinturier, Samuel; ten Kate, Inge; Thomas, Peter; Thompson, Lucy; Tokar, Robert; Toplis, Mike; Torres Redondo, Josefina; Trainer, Melissa; Treiman, Allan; Tretyakov, Vladislav; Urqui-O'Callaghan, Roser; Van Beek, Jason; Van Beek, Tessa; VanBommel, Scott; Vaniman, David; Varenikov, Alexey; Vasavada, Ashwin; Vasconcelos, Paulo; Vicenzi, Edward; Vostrukhin, Andrey; Voytek, Mary; Wadhwa, Meenakshi; Ward, Jennifer; Weigle, Eddie; Wellington, Danika; Westall, Frances; Wiens, Roger Craig; Wilhelm, Mary Beth; Williams, Amy; Williams, Joshua; Williams, Rebecca; Williams, Richard B; Wilson, Mike; Wimmer-Schweingruber, Robert; Wolff, Mike; Wong, Mike; Wray, James; Wu, Megan; Yana, Charles; Yen, Albert; Yingst, Aileen; Zeitlin, Cary; Zimdar, Robert; Zorzano Mier, María-Paz

2013-07-19

Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.

Solvent Hold Tank Sample Results for MCU-16-701-702-703: May 2016 Monthly Sample and MCU-16-710-711-712: May 2016 Superwashed Sample

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

Fondeur, F. F.; Jones, D. H.

The Savannah River National Laboratory (SRNL) received one set of Solvent Hold Tank (SHT) samples (MCU-16-701, MCU-16-702 and MCU-16-703), pulled on 05/23/2016, and another set of SHT samples (MCU-16-710, MCU-16-711, and MCU-16-712) were pulled on 05/28/2016 after the solvent was superwashed with 300 mM sodium hydroxide for analysis. Samples MCU-16-701, MCU-16-702, and MCU-16-703 were combined into one sample (MCU-16-701-702-703) and samples MCU-16-710, MCU- 16-711, and MCU-16-712 were combined into one sample (MCU-16-710-711-712). Of the two composite samples MCU-16-710-711-712 represents the current chemical state of the solvent at MCU. All analytical conclusions are based on the chemical analysis of MCU-16-710-711-712. Theremore » were no chemical differences between MCU-16-701-702-703 and superwashed MCU-16-710-711-712. Analysis of the composited sample MCU-16-710-712-713 indicated the Isopar™L concentration is above its nominal level (102%). The modifier (CS-7SB) is 16% below its nominal concentration, while the TiDG and MaxCalix concentrations are at and above their nominal concentrations, respectively. The TiDG level has begun to decrease, and it is 7% below its nominal level as of May 28, 2016. Based on this current analysis, the levels of TiDG, Isopar™L, MaxCalix, and modifier are sufficient for continuing operation but are expected to decrease with time. Periodic characterization and trimming additions to the solvent are recommended.« less

Evidence for the interaction of the IRS 16 wind with the ionized and molecular gas at the Galactic center

NASA Technical Reports Server (NTRS)

Yusef-Zadeh, Farhad; Wardle, Mark

1993-01-01

We present a number of high-resolution radio images showing evidence for the dynamical interaction of the outflow arising from the IRS 16 complex with the ionized gas associated with the Northern Arm of Sgr A West, and with the northwestern segment of the circumnuclear molecular disk which engulfs the inner few parsecs of the Galactic center. We suggest that the wind disturbs the dynamics of the Northern Arm within 0.1 pc of the center, is responsible for the waviness of the arm at larger distances, and is collimated by Sgr A West and the circumnuclear disk. The waviness is discussed in terms of the Rayleigh-Taylor instability induced by the ram pressure of the wind incident on the surface of the Northern Arm. Another consequence of this interaction is the strong mid-IR polarization of the Northern Arm in the vicinity of the IRS 16 complex which is explained as a result of the ram pressure of the wind compressing the gas and the magnetic field.

Adiabatic and coupled channels calculations for near barrier fusion of 16O +238U using realistic nucleon-nucleon interaction

NASA Astrophysics Data System (ADS)

Ismail, M.; Seif, W. M.; Botros, M. M.

2016-04-01

We investigate the fusion cross-section and the fusion barrier distribution of 16O +238U at near- and sub-barrier energies. We use an interaction potential generated by the semi-microscopic double folding model-based on density dependent (DD) form of the realistic Michigan-three-Yukawa (M3Y) Reid nucleon-nucleon (NN) interaction. We studied the role of both the static and dynamic deformations of the target nucleus on the fusion process. Rotational and vibrational degrees of freedom of 238U-nucleus are considered. We found that the deformation and the octupole vibrations in 238U enhance its sub-barrier fusion cross-section. The signature of the the octupole vibrational modes of 238U appears clearly in its fusion barrier distribution profile.

Laser skin friction measurements and CFD comparison of weak-to-strong swept shock/boundary-layer interactions

NASA Technical Reports Server (NTRS)

Kim, K.-S.; Lee, Y.; Alvi, F. S.; Settles, G. S.; Horstman, C. C.

1990-01-01

A joint experimental and computational study of skin friction in weak-to-strong swept shock wave/turbulent boundary-layer interactions has been carried out. A planar shock wave is generated by a sharp fin at angles of attack alpha = 10 deg and 16 deg at M(infinity) = 3 and 16 and 20 deg at M(infinity) = 4. Measurements are made using the Laser Interferometer Skin Friction meter, which optically detects the rate of thinning of an oil film applied to the test surface. The results show a systematic rise in the peak c(f) at the rear part of the interaction, where the separated flow atttaches. For the stronget case studied, this peak is an order of magnitude higher than the incoming freestream c(f)level.

Platelet Count Mediates the Contribution of a Genetic Variant in LRRC16A to ARDS Risk

PubMed Central

Wei, Yongyue; Wang, Zhaoxi; Su, Li; Chen, Feng; Tejera, Paula; Bajwa, Ednan K.; Wurfel, Mark M.; Lin, Xihong

2015-01-01

BACKGROUND: Platelets are believed to be critical in pulmonary-origin ARDS as mediators of endothelial damage through their interactions with fibrinogen and multiple signal transduction pathways. A prior meta-analysis identified five loci for platelet count (PLT): BAD, LRRC16A, CD36, JMJD1C, and SLMO2. This study aims to validate the quantitative trait loci (QTLs) of PLT within BAD, LRRC16A, CD36, JMJD1C, and SLMO2 among critically ill patients and to investigate the associations of these QTLs with ARDS risk that may be mediated through PLT. METHODS: ARDS cases and at-risk control subjects were recruited from the intensive care unit of the Massachusetts General Hospital. Exome-wide genotyping data of 629 ARDS cases and 1,026 at-risk control subjects and genome-wide gene expression profiles of 18 at-risk control subjects were generated for analysis. RESULTS: Single-nucleotide polymorphism (SNP) rs7766874 within LRRC16A was a significant locus for PLT among at-risk control subjects (β = −13.00; 95% CI, −23.22 to −2.77; P = .013). This association was validated using LRRC16A gene expression data from at-risk control subjects (β = 77.03 per 1 SD increase of log2-transformed expression; 95% CI, 27.26-126.80; P = .005). Further, rs7766874 was associated with ARDS risk conditioned on PLT (OR = 0.68; 95% CI, 0.51-0.90; P = .007), interacting with PLT (OR = 1.15 per effect allele per 100 × 103/μL of PLT; 95% CI, 1.03-1.30; P = .015), and mediated through PLT (indirect OR = 1.045; 95% CI, 1.007-1.085; P = .021). CONCLUSIONS: Our findings support the role of LRRC16A in platelet formation and suggest the importance of LRRC16A in ARDS pathophysiology by interacting with, and being mediated through, platelets. PMID:25254322

Involvement of Escherichia coli in pathogenesis of xanthogranulomatous cholecystitis with scavenger receptor class A and CXCL16-CXCR6 interaction.

PubMed

Sawada, Seiko; Harada, Kenichi; Isse, Kumiko; Sato, Yasunori; Sasaki, Motoko; Kaizaki, Yasuharu; Nakanuma, Yasuni

2007-10-01

Xanthogranulomatous cholecystitis (XGC) is characterized by the infiltration of numerous foamy macrophages. Bacterial infection is thought to be involved in the pathogenesis of XGC. Using XGC and cultured murine biliary epithelial cells (BEC), the participation of E. coli and the role of the scavenger receptor class A (SCARA), as well as chemokine(C-X-C motif) ligand 16 (CXCL16) and its receptor chemokine(C-X-C motif) receptor 6 (CXCR6), were examined in the pathogenesis of XGC. E. coli components and genes were detected in XGC on immunohistochemistry and polymerase chain reaction (PCR), respectively. SCARA-recognizing E. coli was found in foamy macrophages aggregated in xanthogranulomatous lesions. CXCL16, which functions as a membrane-bound molecule and soluble chemokine to induce adhesion and migration of CXCR6(+) cells, was detected on gallbladder epithelia, and CXCR6(+)/CD8(+) T cells and CXCR6(+)/CD68(+) macrophages were also accumulated. In cultured BEC, CXCL16 mRNA and secreted soluble CXCL16 were constantly detected and upregulated by treatment with E. coli and lipopolysaccharide through Toll-like receptor 4. These suggest that SCARA in macrophages is involved in the phagocytosis of E. coli followed by foamy changes and that bacterial infection causes the upregulation of CXCL16 in gallbladder epithelia, leading to the chemoattraction of macrophages via CXCL16-CXCR6 interaction and formation of the characteristic histology of XGC.

75 FR 22503 - Airworthiness Directives; Bombardier, Inc. Model DHC-8-400 Series Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-29

... an inrush current less than or equal to 1.6 amps, before further flight, replace the vane with a new... AOA vane is found to have an inrush current greater than 1.6 amps, repeat the measurement of the vane... the serviceable AOA transducer is-- Then repeat the measurement-- More than 1.60 amps, but less than...

Evidence for neutrino oscillations in the Sudbury Neutrino Observatory

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

Marino, Alysia Diane

2004-01-01

The Sudbury Neutrino Observatory (SNO) is a large-volume heavy water Cerenkov detector designed to resolve the solar neutrino problem. SNO observes charged-current interactions with electron neutrinos, neutral-current interactions with all active neutrinos, and elastic-scattering interactions primarily with electron neutrinos with some sensitivity to other flavors. This dissertation presents an analysis of the solar neutrino flux observed in SNO in the second phase of operation, while ~2 tonnes of salt (NaCl) were dissolved in the heavy water. The dataset here represents 391 live days of data. Only the events above a visible energy threshold of 5.5 MeV and inside a fiducial volume within 550 cm of the center of the detector are studied. The neutrino flux observed via the charged-current interaction is [1.71 ± 0.065(stat.)±more » $$0.065\\atop{0.068}$$(sys.)±0.02(theor.)] x 10 6cm -2s -1, via the elastic-scattering interaction is [2.21±0.22(stat.)±$$0.12\\atop{0.11}$$(sys.)±0.01(theor.)] x 10 6cm -2s -1, and via the neutral-current interaction is [5.05±0.23(stat.)±$$0.31\\atop{0.37}$$(sys.)±0.06(theor.)] x 10 6cm -2s -1. The electron-only flux seen via the charged-current interaction is more than 7σ below the total active flux seen via the neutral-current interaction, providing strong evidence that neutrinos are undergoing flavor transformation as they travel from the core of the Sun to the Earth. The most likely origin of the flavor transformation is matter-induced flavor oscillation.« less

Is Attachment at Ages 1, 6 and 16 Related to Autonomy and Relatedness Behavior of Adolescents in Interaction towards Their Mothers?

ERIC Educational Resources Information Center

Becker-Stoll, Fabienne; Fremmer-Bombik, Elisabeth; Wartner, Ulrike; Zimmermann, Peter; Grossmann, Klaus E.

2008-01-01

This study investigates whether attachment quality at ages 1, 6 and 16 is related to autonomy and relatedness behavior in adolescence. In a follow-up of the Regensburg Longitudinal Study, forty-three 16-year-old adolescents and their mothers were assessed in a revealed differences task and a planning a vacation task. Attachment was assessed during…

Non-covalently anchored multi-walled carbon nanotubes with hexa-decafluorinated zinc phthalocyanine as ppb level chemiresistive chlorine sensor

NASA Astrophysics Data System (ADS)

Sharma, Anshul Kumar; Mahajan, Aman; Bedi, R. K.; Kumar, Subodh; Debnath, A. K.; Aswal, D. K.

2018-01-01

A cost effective solution assembly method has been explored for preparing zinc(II)1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexa-decafluoro-29H,31H-phthalocyanine/multi-walled carbon nanotubes (F16ZnPc/MWCNTs-COOH) hybrid. Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) investigations confirm the non-covalent anchoring of F16ZnPc onto MWCNTs-COOH through п-п stacking interactions. Further, a highly sensitive and selective chemiresistive Cl2 sensor has been fabricated using F16ZnPc/MWCNTs-COOH hybrid. The response of sensor is found to be 21.28% for 2 ppm of Cl2 with a response time of 14 s and theoretical detection limit of the sensor is found down to 0.06 ppb. The improved Cl2 sensing characteristics of hybrid are found to be originated from the synergetic interaction between F16ZnPc and MWCNTs-COOH. The underlying mechanism for improved gas sensing performance of F16ZnPc/MWCNTs-COOH sensor towards Cl2 has been explained using Raman, X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS) studies.

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota

PubMed Central

Ellegaard, Kirsten M.; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities. PMID:27708630

Beyond 16S rRNA Community Profiling: Intra-Species Diversity in the Gut Microbiota.

PubMed

Ellegaard, Kirsten M; Engel, Philipp

2016-01-01

Interactions with microbes affect many aspects of animal biology, including immune system development, nutrition and health. In vertebrates, the gut microbiota is dominated by a small subset of phyla, but the species composition within these phyla is typically not conserved. Moreover, several recent studies have shown that bacterial species in the gut are composed of a multitude of strains, which frequently co-exist in their host, and may be host-specific. However, since the study of intra-species diversity is challenging, particularly in the setting of complex, host-associated microbial communities, our current understanding of the distribution, evolution and functional relevance of intra-species diversity in the gut is scarce. In order to unravel how genomic diversity translates into phenotypic diversity, community analyses going beyond 16S rRNA profiling, in combination with experimental approaches, are needed. Recently, the honeybee has emerged as a promising model for studying gut bacterial communities, particularly in terms of strain-level diversity. Unlike most other invertebrates, the honeybee gut is colonized by a remarkably consistent and specific core microbiota, which is dominated by only eight bacterial species. As for the vertebrate gut microbiota, these species are composed of highly diverse strains suggesting that similar evolutionary forces shape gut community structures in vertebrates and social insects. In this review, we outline current knowledge on the evolution and functional relevance of strain diversity within the gut microbiota, including recent insights gained from mammals and other animals such as the honeybee. We discuss methodological approaches and propose possible future avenues for studying strain diversity in complex bacterial communities.

Opinions of Female Juvenile Delinquents about Their Interactions in Chat Rooms

ERIC Educational Resources Information Center

Sanger, Dixie; Long, Amie; Ritzman, Mitzi; Stofer, Keri; Davis, Candy

2004-01-01

The purpose of this study was to survey the opinions of 62 adolescent females residing in a correctional facility about their use of the Internet to participate in chat room conversations. Findings indicated that 54 of 62 girls (87.09%), with a mean age of 16.72 years, participated in chat room interactions. Most (n = 47) interacted in chat rooms…

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery.

PubMed

Merath, Katiuscha; Chen, Qinyu; Bagante, Fabio; Akgul, Ozgur; Idrees, Jay J; Dillhoff, Mary; Cloyd, Jordan M; Pawlik, Timothy M

2018-06-18

Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p < 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2-19.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6-83.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3-199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4-18.7). Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality.

Interactive Exposure With a Blood Glucose Monitor With a Novel Glucose Color Range Indicator Is Associated With Improved Glucose Range Interpretation and Awareness in Patients With Type 2 Diabetes.

PubMed

Grady, Mike; Warren, Graham; Levy, Brian L; Katz, Laurence B

2015-07-01

The ability of patients to achieve glycemic control depends in part on their ability to interpret and act on blood glucose (BG) results. This clinical study was conducted to determine if a simple on-meter color range indicator (CRI) could improve the ability of patients to categorize BG values into low, in-range, and high glycemic ranges. The clinical study was conducted in 59 subjects with type 2 diabetes (T2DM). Subjects classified 50 general, 15 before- and 15 after-meal BG values as low, in-range, or high based on their current knowledge. Subjects then interactively experienced the on-meter CRI, which showed whether alternate BG values were low, in-range, or high. After CRI interaction, subjects repeated the original scoring assessment followed by a survey exploring their awareness of glucose ranges. Following interaction with the CRI, subjects improved their ability to categorize general, before-meal and after-meal BG results by 23.4% ± 3.0% (SEM), 14.2% ± 2.4%, and 16.1% ± 2.9%, respectively (all P < .001), into low, in-range, and high glycemic ranges. Improvement was not accompanied by an increase in time spent categorizing results. There was no correlation between subject HbA1c, test frequency, or duration of diabetes and ability to correctly classify results. Subjects agreed the CRI feature helped them easily interpret glucose values and improved their awareness of glucose ranges. A short interactive session with a meter including a CRI feature improved the ability of T2DM subjects to interpret and categorize BG values into recommended ranges. © 2015 Diabetes Technology Society.

Preferred Learning Style and Educational Technology: Linear vs. Interactive Video.

ERIC Educational Resources Information Center

Yoder, Marianne E.

1994-01-01

A study found that learners with reflective-observing learning styles (n=16) tend to learn better with linear video, and those with active experimenting learning styles (n=42) tend to achieve greater learning with computer-assisted interactive video instruction. (JOW)

The Density Functional Theory of Flies: Predicting distributions of interacting active organisms

NASA Astrophysics Data System (ADS)

Kinkhabwala, Yunus; Valderrama, Juan; Cohen, Itai; Arias, Tomas

On October 2nd, 2016, 52 people were crushed in a stampede when a crowd panicked at a religious gathering in Ethiopia. The ability to predict the state of a crowd and whether it is susceptible to such transitions could help prevent such catastrophes. While current techniques such as agent based models can predict transitions in emergent behaviors of crowds, the assumptions used to describe the agents are often ad hoc and the simulations are computationally expensive making their application to real-time crowd prediction challenging. Here, we pursue an orthogonal approach and ask whether a reduced set of variables, such as the local densities, are sufficient to describe the state of a crowd. Inspired by the theoretical framework of Density Functional Theory, we have developed a system that uses only measurements of local densities to extract two independent crowd behavior functions: (1) preferences for locations and (2) interactions between individuals. With these two functions, we have accurately predicted how a model system of walking Drosophila melanogaster distributes itself in an arbitrary 2D environment. In addition, this density-based approach measures properties of the crowd from only observations of the crowd itself without any knowledge of the detailed interactions and thus it can make predictions about the resulting distributions of these flies in arbitrary environments, in real-time. This research was supported in part by ARO W911NF-16-1-0433.

The Hα kinematics of interacting galaxies in 12 compact groups★

NASA Astrophysics Data System (ADS)

Torres-Flores, S.; Amram, P.; Mendes de Oliveira, C.; Plana, H.; Balkowski, C.; Marcelin, M.; Olave-Rojas, D.

2014-08-01

We present new Fabry-Perot observations for a sample of 42 galaxies located in 12 compact groups of galaxies: HCG 1, HCG 14, HCG 25, HCG 44, HCG 53, HCG 57, HCG 61, HCG 69, HCG 93, VV 304, LGG 455 and Arp 314. From the 42 observed galaxies, a total of 26 objects are spiral galaxies, which range from Sa to Im morphological types. The remaining 16 objects are E, S0 and S0a galaxies. Using these observations, we have derived velocity maps, monochromatic and velocity dispersion maps for 24 galaxies, where 18 are spiral, three are S0a, two are S0 and one is an Im galaxy. From the 24 velocity fields obtained, we could derive rotation curves for 15 galaxies; only two of them exhibit rotation curves without any clear signature of interactions. Based on kinematic information, we have evaluated the evolutionary stage of the different groups of the current sample. We identify groups that range from having no Hα emission to displaying an extremely complex kinematics, where their members display strongly perturbed velocity fields and rotation curves. In the case of galaxies with no Hα emission, we suggest that past galaxy interactions removed their gaseous components, thereby quenching their star formation. However, we cannot discard that the lack of Hα emission is linked with the detection limit for some of our observations.

PERSISTENT CURRENT EFFECT IN 15-16 T NB3SN ACCELERATOR DIPOLES AND ITS CORRECTION

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

Kashikhin, V. V.; Zlobin, A. V.

2016-11-08

Nb3Sn magnets with operating fields of 15-16 T are considered for the LHC Energy Doubler and a future Very High Energy pp Collider. Due to large coil volume, high critical current density and large superconducting (SC) filament size the persistent current effect is very large in Nb3Sn dipoles al low fields. This paper presents the results of analysis of the persistent current effect in the 15 T Nb3Sn dipole demonstrator being developed at FNAL, and describes different possibilities of its correction including passive SC wires, iron shims and coil geometry.

Metal-loaded SBA-16-like silica - Correlation between basicity and affinity towards hydrogen

NASA Astrophysics Data System (ADS)

Ouargli-Saker, R.; Bouazizi, N.; Boukoussa, B.; Barrimo, Diana; Paola-Nunes-Beltrao, Ana-.; Azzouz, A.

2017-07-01

Nanoparticles of Cuo (CuNPs) and Feo (FeNPs) were dispersed in SBA-16-like silica, resulting metal-loaded materials (Cu-SBA-16 and Fe-SBA-16) with improved affinity towards hydrogen. Electron microscopy and X-ray diffraction showed that MNP dispersion occurs mainly inside SBA-16 channels. MNP incorporation was found to confer affinity to the silica surface, since higher CO2 retention capacity (CRC) was registered Cu/SBA-16 and Fe/SBA-16. This was accompanied by a significant improvement of the affinity towards hydrogen, as supported by hydrogen adsorption tests. This was explained in terms of strong hydrogen interaction with MNP and lattice oxygen atoms. The results reported herein open new prospects for SBA-16 as potential adsorbents for hydrogen storage.

Time-dependent photon heat transport through a mesoscopic Josephson device

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

Lu, Wen-Ting; Zhao, Hong-Kang, E-mail: zhaohonk@bit.edu.cn

The time-oscillating photon heat current through a dc voltage biased mesoscopic Josephson Junction (MJJ) has been investigated by employing the nonequilibrium Green’s function approach. The Landauer-like formula of photon heat current has been derived in both of the Fourier space and its time-oscillating versions, where Coulomb interaction, self inductance, and magnetic flux take effective roles. Nonlinear behaviors are exhibited in the photon heat current due to the quantum nature of MJJ and applied external dc voltage. The magnitude of heat current decreases with increasing the external bias voltage, and subtle oscillation structures appear as the superposition of different photon heatmore » branches. The overall period of heat current with respect to time is not affected by Coulomb interaction, however, the magnitude and phase of it vary considerably by changing the Coulomb interaction. - Highlights: • The time-oscillating photon heat current through a mesoscopic Josephson Junction has been investigated. • The Landauer-like formula of photon heat current has been derived by the nonequilibrium Green’s function approach. • Nonlinear behaviors are exhibited in the photon heat current resulting from the self inductance and Coulomb interaction. • The oscillation structure of heat current is composed of the superposition of oscillations with different periods.« less

A Cryo-Electron Microscopy Study Identifies the Complete H16.V5 Epitope and Reveals Global Conformational Changes Initiated by Binding of the Neutralizing Antibody Fragment

PubMed Central

Lee, Hyunwook; Brendle, Sarah A.; Bywaters, Stephanie M.; Guan, Jian; Ashley, Robert E.; Yoder, Joshua D.; Makhov, Alexander M.; Conway, James F.; Christensen, Neil D.

2014-01-01

ABSTRACT Human papillomavirus 16 (HPV16) is a worldwide health threat and an etiologic agent of cervical cancer. To understand the antigenic properties of HPV16, we pursued a structural study to elucidate HPV capsids and antibody interactions. The cryo-electron microscopy (cryo-EM) structures of a mature HPV16 particle and an altered capsid particle were solved individually and as complexes with fragment of antibody (Fab) from the neutralizing antibody H16.V5. Fitted crystal structures provided a pseudoatomic model of the virus-Fab complex, which identified a precise footprint of H16.V5, including previously unrecognized residues. The altered-capsid–Fab complex map showed that binding of the Fab induced significant conformational changes that were not seen in the altered-capsid structure alone. These changes included more ordered surface loops, consolidated so-called “invading-arm” structures, and tighter intercapsomeric connections at the capsid floor. The H16.V5 Fab preferentially bound hexavalent capsomers likely with a stabilizing effect that directly correlated with the number of bound Fabs. Additional cryo-EM reconstructions of the virus-Fab complex for different incubation times and structural analysis provide a model for a hyperstabilization of the capsomer by H16.V5 Fab and showed that the Fab distinguishes subtle differences between antigenic sites. IMPORTANCE Our analysis of the cryo-EM reconstructions of the HPV16 capsids and virus-Fab complexes has identified the entire HPV.V5 conformational epitope and demonstrated a detailed neutralization mechanism of this clinically important monoclonal antibody against HPV16. The Fab bound and ordered the apical loops of HPV16. This conformational change was transmitted to the lower region of the capsomer, resulting in enhanced intercapsomeric interactions evidenced by the more ordered capsid floor and “invading-arm” structures. This study advances the understanding of the neutralization mechanism used by H16.V5. PMID:25392224

Evaluating wave-current interaction in an urban estuary and flooding implications for coastal communities

NASA Astrophysics Data System (ADS)

Cifuentes-Lorenzen, A.; O'Donnell, J.; Howard-Strobel, M. M.; Fake, T.; McCardell, G.

2016-12-01

Accurate hydrodynamic-wave coupled coastal circulation models aid the prediction of storm impacts, particularly in areas where data is absent, and can inform mitigation options. They are essential everywhere to account for the effects of climate change. Here, the Finite Volume Community Ocean Model (FVCOM) was used to estimate the residual circulation inside a small urban estuary, Long Island Sound, during three severe weather events of different magnitude (i.e. 1/5, 1/25 and 1/50 year events). The effect of including wave coupling using a log-layer bottom boundary and the bottom wave-current coupling, following the approach of Madsen (1994) on the simulated residual circulation was assessed. Significant differences in the solutions were constrained to the near surface (s>-0.3) region. No significant difference in the depth-averaged residual circulation was detected. When the Madsen (1994) bottom boundary layer model for wave-current interaction was employed, differences in residual circulation resulted. The bottom wave-current interaction also plays an important role in the wave dynamics. Significant wave heights along the northern Connecticut shoreline were enhanced by up to 15% when the bottom wave-current interaction was included in the simulations. The wave-induced bottom drag enhancement has a substantial effect on tides in the Sound, possibly because it is nearly resonant at semidiurnal frequencies. This wave-current interaction current leads to severe tidal dampening ( 40% amplitude reduction) at the Western end of the estuary in the modeled sea surface displacement. The potential magnitude of these effects means that wave current interaction should be included and carefully evaluated in models of estuaries that are useful.

THE ESTROGENS / CHROMIUM INTERACTION IN THE NITRIC OXIDE GENERATION.

PubMed

Sawicka, Ewa; Piwowar, Agnieszka; Musiala, Tomasz; Dlugosz, Anna

2017-05-01

The interaction of estrogens with environmental toxins in free radicals generation: reactive oxygen species (ROS) or reactive nitrogen species (RNS) which participates in cancerogenesis is not yet recognized. Chromium(VI) is widely present in environment. One of its toxicity pathway is free radicals generation. Estrogens have the ability to scavenge free radicals, but may also act as prooxidants. Both chromium(VI) and estrogens are classified by International Agency for Research on Cancer (IARC) as carcinogens, so synergistic effect seems very dangerous. The interaction of chromium and estrogens in ROS generation are partly described but there are no reports on estrogen/chromium interaction on nitric oxide (NO) generation. The aim of the study was to examine the interaction of chromium(VI) and 17-p-estradiol (E2) on NO level in human blood as well as the role of E2 metabolites: 4-hydroxyestradiol (4-OHE2) and 16a-hydroxyestrone (16α-OHE1) in these processes. The NO level was estimated with the diagnostic kit (Nitric Oxide Colorimetric Detection Kit from Arbor Assays) in human blood in vitm. The results showed that Cr(VI) in used concentration (0.5; 1.0 and 5.0 gg/mL) decreases significantly NO level in blood, acting antagonistically to E2 and 4-OHE2. Estrogens (E2, 4-OHE2 and 16α-OHEI) do not protect against inhibiting effect of Cr(VI) on nitric oxide generation in blood because after combined exposure the decreased production of NO in blood was noted. In conclusion, presented results provide the information about the character of estrogen/Cr(VI) interaction in NO level in human blood. It is important knowledge for cardio protected effect e.g., hormone replacement therapy in environmental or occupational exposure to Cr(VI), chromium supplementation, also important for cancer risk evaluation.

Progress Report for DOE DE-FG03-98ER20317 ''Regulation of the floral homeotic gene AGAMOUS'' Current and Final Funding Period: September 1, 2002, to December 31, 2002

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

Weigel, D.

2003-03-11

OAK-B135 Results obtained during this funding period: (1) Phylogenetic footprinting of AG regulatory sequences Sequences necessary and sufficient for AGAMOUS (AG) expression in the center of Arabidopsis flowers are located in the second intron, which is about 3 kb in size. This intron contains binding sites for two transcription factors, LEAFY (LFY) and WUSCHEL (WUS), which are direct activators of AG. We used the new method of phylogenetic shadowing to identify new regulatory elements. Among 29 Brassicaceae, several other motifs, but not the LFY and WUS binding sites previously identified, are largely invariant. Using reporter gene analyses, we tested sixmore » of these motifs and found that they are all functionally important for activity of AG regulatory sequences in A. thaliana. (2) Repression of AG by MADS box genes A candidate for repressing AG in the shoot apical meristem has been the MADS box gene FUL, since it is expressed in the shoot apical meristem and since an activated version (FUL:VP16) leads to ectopic AG expression in the shoot apical meristem. However, there is no ectopic AG expression in full single mutants. We therefore started to generate VP16 fusions of several other MADS box genes expressed in the shoot apical meristem, to determine which of these might be candidates for FUL redundant genes. We found that AGL6:VP16 has a similar phenotype as FUL:VP16, suggesting that AGL6 and FUL interact. We are now testing this hypothesis. (3) Two candidate AG regulators, WOW and ULA Because the phylogenetic footprinting project has identified several new candidate regulatory motifs, of which at least one (the CCAATCA motif) has rather strong effects, we had decided to put the analysis of WOW and ULA on hold, and to focus on using the newly identified motifs as tools. We conduct ed yeast one-hybrid screen with two of the conserved motifs, and identified several classes of transcription factors that can interact with them. One of these is encoded by the PAN gene, previously known to be expressed in a domain that overlaps the AG domain, but not known before to regulate AG. (4) New genetic modifiers of AG This part of the project was concluded in the previous funding period.« less

Casimir Interaction from Magnetically Coupled Eddy Currents

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

Intravaia, Francesco; Henkel, Carsten

2009-09-25

We study the quantum and thermal fluctuations of eddy (Foucault) currents in thick metallic plates. A Casimir interaction between two plates arises from the coupling via quasistatic magnetic fields. As a function of distance, the relevant eddy current modes cross over from a quantum to a thermal regime. These modes alone reproduce previously discussed thermal anomalies of the electromagnetic Casimir interaction between good conductors. In particular, they provide a physical picture for the Casimir entropy whose nonzero value at zero temperature arises from a correlated, glassy state.

Effects of hybrid cycling versus handcycling on wheelchair-specific fitness and physical activity in people with long-term spinal cord injury: a 16-week randomized controlled trial.

PubMed

Bakkum, A J T; de Groot, S; Stolwijk-Swüste, J M; van Kuppevelt, D J; van der Woude, L H V; Janssen, T W J

2015-05-01

This is an open randomized controlled trial. The objective of this study was to investigate the effects of a 16-week hybrid cycle versus handcycle exercise program on fitness and physical activity in inactive people with long-term spinal cord injury (SCI). The study was conducted in two rehabilitation centers with a specialized SCI unit. Twenty individuals (SCI⩾8 years) were randomly assigned to a hybrid cycle (voluntary arm exercise combined with functional electrical stimulation (FES)-induced leg exercise) or a handcycle group. During 16 weeks, both groups trained twice a week for 30 min at 65-75% heart rate reserve. Outcome measures obtained before, during and after the program were fitness (peak power output, peak oxygen consumption), submaximal VO2 and heart rate (HR), resting HR, wheelchair skill performance time score) and physical activity (distance travelled in wheelchair and Physical Activity Scale for Individuals with Physical Disabilities (PASIPD) score). Changes were examined using a two-factor mixed-measures analysis of variance. For all fitness parameters, except for submaximal VO2, no interaction effects were found. The hybrid cycle group showed a decrease in VO2 over time in contrast to the handcycle group (P=0.045). An overall reduction in HRrest (5±2 b.p.m.; P=0.03) and overall increase in PASIPD score (6.5±2.1; P=0.002) were found after 16 weeks of training. No overall training effects were found for the other fitness and activity outcome measures. In the current study, hybrid cycling and handcycling showed similar effects on fitness and physical activity, indicating that there seem to be no additional benefits of the FES-induced leg exercise over handcycle training alone.

21cm Absorption Line Zeeman Observations And Modeling Of Physical Conditions In M16

NASA Astrophysics Data System (ADS)

Kiuchi, Furea; Brogan, C.; Troland, T.

2011-01-01

We present detailed 21 cm HI absorption line observations of M16 using the Very Large Array. The M16 "pillars of creation" are classic examples of the interaction of ISM with radiation from young, hot stars. Magnetic fields can affect these interactions, the 21 cm Zeeman effect reveals magnetic field strengths in the Photodissociation regions associated with the pillars. The present results yield a 3-sigma upper limit upon the line-of-sight magnetic field of about 300 microgauss. This limit is consistent with a total field strength of 500 microgauss, required in the molecular gas if magnetic energies and turbulent energies in the pillars are in equipartition. Most likely, magnetic fields do not play a dominant role in the dynamics of the M16 pillars. Another goal of this study is to determine the distribution of cold HI in the M16 region and to model the physical conditions in the neutral gas in the pillars. We used the spectral synthesis code Cloudy 08.00 for this purpose. We adopted the results of a published Cloudy HII region model and extended this model into the neutral gas to derive physical conditions therein.

The Barley Powdery Mildew Candidate Secreted Effector Protein CSEP0105 Inhibits the Chaperone Activity of a Small Heat Shock Protein1[OPEN

PubMed Central

Ahmed, Ali Abdurehim; Pedersen, Carsten; Schultz-Larsen, Torsten; Kwaaitaal, Mark; Jørgensen, Hans Jørgen Lyngs; Thordal-Christensen, Hans

2015-01-01

Pathogens secrete effector proteins to establish a successful interaction with their host. Here, we describe two barley (Hordeum vulgare) powdery mildew candidate secreted effector proteins, CSEP0105 and CSEP0162, which contribute to pathogen success and appear to be required during or after haustorial formation. Silencing of either CSEP using host-induced gene silencing significantly reduced the fungal haustorial formation rate. Interestingly, both CSEPs interact with the barley small heat shock proteins, Hsp16.9 and Hsp17.5, in a yeast two-hybrid assay. Small heat shock proteins are known to stabilize several intracellular proteins, including defense-related signaling components, through their chaperone activity. CSEP0105 and CSEP0162 localized to the cytosol and the nucleus of barley epidermal cells, whereas Hsp16.9 and Hsp17.5 are cytosolic. Intriguingly, only those specific CSEPs changed localization and became restricted to the cytosol when coexpressed with Hsp16.9 and Hsp17.5, confirming the CSEP-small heat shock protein interaction. As predicted, Hsp16.9 showed chaperone activity, as it could prevent the aggregation of Escherichia coli proteins during thermal stress. Remarkably, CSEP0105 compromised this activity. These data suggest that CSEP0105 promotes virulence by interfering with the chaperone activity of a barley small heat shock protein essential for defense and stress responses. PMID:25770154

Sol Gel-Derived SBA-16 Mesoporous Material

PubMed Central

Rivera-Muñoz, Eric M.; Huirache-Acuña, Rafael

2010-01-01

The aim of this article is to review current knowledge related to the synthesis and characterization of sol gel-derived SBA-16 mesoporous silicas, as well as a review of the state of the art in this issue, to take stock of knowledge about current and future applications. The ease of the method of preparation, the orderly structure, size and shape of their pores and control, all these achievable through simple changes in the method of synthesis, makes SBA-16 a very versatile material, potentially applicable in many areas of science and molecular engineering of materials. PMID:20957080

Use of Vortex Generators to Reduce Distortion for Mach 1.6 Streamline-Traced Supersonic Inlets

NASA Technical Reports Server (NTRS)

Baydar, Ezgihan; Lu, Frank; Slater, John W.; Trefny, Chuck

2016-01-01

Reduce the total pressure distortion at the engine-fan face due to low-momentum flow caused by the interaction of an external terminal shock at the turbulent boundary layer along a streamline-traced external-compression (STEX) inlet for Mach 1.6.

PREFACE: XXX International Conference on Interaction of Intense Energy Fluxes with Matter

NASA Astrophysics Data System (ADS)

Fortov, V. E.; Khishchenko, K. V.; Karamurzov, B. S.; Efremov, V. P.; Sultanov, V. G.

2015-11-01

This paper is a preface to the proceedings of the XXX International Conference on Interaction of Intense Energy Fluxes with Matter, which was held in Elbrus settlement, in the Kabardino-Balkar Republic of the Russian Federation, from March 1-6, 2015.

Influence of scale interaction on the transport of a passive scalar in a turbulent boundary layer

NASA Astrophysics Data System (ADS)

Saxton-Fox, Theresa; Dawson, Scott; McKeon, Beverley

2017-11-01

A mildly heated turbulent boundary layer is experimentally studied using particle image velocimetry to measure the velocity field and a Malley probe (Malley et al., 1992; Gordeyev et al., 2014) to measure the passive scalar field. Strong gradients in the passive scalar field are observed to be correlated to the interaction of specific velocity scales, illuminating an effect of scale interaction on the passive scalar field. A resolvent analysis performed on the fluctuating velocity and passive scalar equations of motion is used to identify the most amplified velocity and scalar mode shapes at particular wavenumbers. The superposition of a small number of these modes is shown to reproduce the velocity scale interaction phenomenon observed experimentally, as well as the corresponding strong gradient in the scalar field. This work was made possible through the support of United States Air Force Grants FA9550-16-1-0361 and FA9550-16-1-0232 as well as a National Defense Science and Engineering Graduate (NDSEG) fellowship.

Auxiliary field diffusion Monte Carlo calculations of light and medium-mass nuclei with local chiral interactions

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

Lonardoni, D.; Gandolfi, S.; Lynn, J. E.

Quantum Monte Carlo methods have recently been employed to study properties of nuclei and infinite matter using local chiral effective-field-theory interactions. In this paper, we present a detailed description of the auxiliary field diffusion Monte Carlo algorithm for nuclei in combination with local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We show results for the binding energy, charge radius, charge form factor, and Coulomb sum rule in nuclei withmore » $$3{\\le}A{\\le}16$$. Particular attention is devoted to the effect of different operator structures in the three-body force for different cutoffs. Finally, the outcomes suggest that local chiral interactions fit to few-body observables give a very good description of the ground-state properties of nuclei up to $$^{16}\\mathrm{O}$$, with the exception of one fit for the softer cutoff which predicts overbinding in larger nuclei.« less

Auxiliary field diffusion Monte Carlo calculations of light and medium-mass nuclei with local chiral interactions

DOE PAGES

Lonardoni, D.; Gandolfi, S.; Lynn, J. E.; ...

2018-04-24

Quantum Monte Carlo methods have recently been employed to study properties of nuclei and infinite matter using local chiral effective-field-theory interactions. In this paper, we present a detailed description of the auxiliary field diffusion Monte Carlo algorithm for nuclei in combination with local chiral two- and three-nucleon interactions up to next-to-next-to-leading order. We show results for the binding energy, charge radius, charge form factor, and Coulomb sum rule in nuclei withmore » $$3{\\le}A{\\le}16$$. Particular attention is devoted to the effect of different operator structures in the three-body force for different cutoffs. Finally, the outcomes suggest that local chiral interactions fit to few-body observables give a very good description of the ground-state properties of nuclei up to $$^{16}\\mathrm{O}$$, with the exception of one fit for the softer cutoff which predicts overbinding in larger nuclei.« less

Molecular dynamics simulations demonstrate the regulation of DNA-DNA attraction by H4 histone tail acetylations and mutations.

PubMed

Korolev, Nikolay; Yu, Hang; Lyubartsev, Alexander P; Nordenskiöld, Lars

2014-10-01

The positively charged N-terminal histone tails play a crucial role in chromatin compaction and are important modulators of DNA transcription, recombination, and repair. The detailed mechanism of the interaction of histone tails with DNA remains elusive. To model the unspecific interaction of histone tails with DNA, all-atom molecular dynamics (MD) simulations were carried out for systems of four DNA 22-mers in the presence of 20 or 16 short fragments of the H4 histone tail (variations of the 16-23 a. a. KRHRKVLR sequence, as well as the unmodified fragment a. a.13-20, GGAKRHRK). This setup with high DNA concentration, explicit presence of DNA-DNA contacts, presence of unstructured cationic peptides (histone tails) and K(+) mimics the conditions of eukaryotic chromatin. A detailed account of the DNA interactions with the histone tail fragments, K(+) and water is presented. Furthermore, DNA structure and dynamics and its interplay with the histone tail fragments binding are analysed. The charged side chains of the lysines and arginines play major roles in the tail-mediated DNA-DNA attraction by forming bridges and by coordinating to the phosphate groups and to the electronegative sites in the minor groove. Binding of all species to DNA is dynamic. The structure of the unmodified fully-charged H4 16-23 a.a. fragment KRHRKVLR is dominated by a stretched conformation. The H4 tail a. a. fragment GGAKRHRK as well as the H4 Lys16 acetylated fragment are highly flexible. The present work allows capturing typical features of the histone tail-counterion-DNA structure, interaction and dynamics. © 2014 Wiley Periodicals, Inc.

Flux quench in a system of interacting spinless fermions in one dimension

NASA Astrophysics Data System (ADS)

Nakagawa, Yuya O.; Misguich, Grégoire; Oshikawa, Masaki

2016-05-01

We study a quantum quench in a one-dimensional spinless fermion model (equivalent to the XXZ spin chain), where a magnetic flux is suddenly switched off. This quench is equivalent to imposing a pulse of electric field and therefore generates an initial particle current. This current is not a conserved quantity in the presence of a lattice and interactions, and we investigate numerically its time evolution after the quench, using the infinite time-evolving block decimation method. For repulsive interactions or large initial flux, we find oscillations that are governed by excitations deep inside the Fermi sea. At long times we observe that the current remains nonvanishing in the gapless cases, whereas it decays to zero in the gapped cases. Although the linear response theory (valid for a weak flux) predicts the same long-time limit of the current for repulsive and attractive interactions (relation with the zero-temperature Drude weight), larger nonlinearities are observed in the case of repulsive interactions compared with that of the attractive case.

Gene–environment interactions involving functional variants: Results from the Breast Cancer Association Consortium

PubMed Central

Barrdahl, Myrto; Rudolph, Anja; Hopper, John L.; Southey, Melissa C.; Broeks, Annegien; Fasching, Peter A.; Beckmann, Matthias W.; Gago‐Dominguez, Manuela; Castelao, J. Esteban; Guénel, Pascal; Truong, Thérèse; Bojesen, Stig E.; Gapstur, Susan M.; Gaudet, Mia M.; Brenner, Hermann; Arndt, Volker; Brauch, Hiltrud; Hamann, Ute; Mannermaa, Arto; Lambrechts, Diether; Jongen, Lynn; Flesch‐Janys, Dieter; Thoene, Kathrin; Couch, Fergus J.; Giles, Graham G.; Simard, Jacques; Goldberg, Mark S.; Figueroa, Jonine; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Eilber, Ursula; Behrens, Sabine; Czene, Kamila; Hall, Per; Cox, Angela; Cross, Simon; Swerdlow, Anthony; Schoemaker, Minouk J.; Dunning, Alison M.; Kaaks, Rudolf; Pharoah, Paul D.P.; Schmidt, Marjanka; Garcia‐Closas, Montserrat; Easton, Douglas F.; Milne, Roger L.

2017-01-01

Investigating the most likely causal variants identified by fine‐mapping analyses may improve the power to detect gene–environment interactions. We assessed the interplay between 70 single nucleotide polymorphisms identified by genetic fine‐scale mapping of susceptibility loci and 11 epidemiological breast cancer risk factors in relation to breast cancer. Analyses were conducted on up to 58,573 subjects (26,968 cases and 31,605 controls) from the Breast Cancer Association Consortium, in one of the largest studies of its kind. Analyses were carried out separately for estrogen receptor (ER) positive (ER+) and ER negative (ER–) disease. The Bayesian False Discovery Probability (BFDP) was computed to assess the noteworthiness of the results. Four potential gene–environment interactions were identified as noteworthy (BFDP < 0.80) when assuming a true prior interaction probability of 0.01. The strongest interaction result in relation to overall breast cancer risk was found between CFLAR‐rs7558475 and current smoking (ORint = 0.77, 95% CI: 0.67–0.88, p int = 1.8 × 10−4). The interaction with the strongest statistical evidence was found between 5q14‐rs7707921 and alcohol consumption (ORint =1.36, 95% CI: 1.16–1.59, p int = 1.9 × 10−5) in relation to ER– disease risk. The remaining two gene–environment interactions were also identified in relation to ER– breast cancer risk and were found between 3p21‐rs6796502 and age at menarche (ORint = 1.26, 95% CI: 1.12–1.43, p int =1.8 × 10−4) and between 8q23‐rs13267382 and age at first full‐term pregnancy (ORint = 0.89, 95% CI: 0.83–0.95, p int = 5.2 × 10−4). While these results do not suggest any strong gene–environment interactions, our results may still be useful to inform experimental studies. These may in turn, shed light on the potential interactions observed. PMID:28670784

Interactive visualization for scar transmurality in cardiac resynchronization therapy

NASA Astrophysics Data System (ADS)

Reiml, Sabrina; Toth, Daniel; Panayiotou, Maria; Fahn, Bernhard; Karim, Rashed; Behar, Jonathan M.; Rinaldi, Christopher A.; Razavi, Reza; Rhode, Kawal S.; Brost, Alexander; Mountney, Peter

2016-03-01

Heart failure is a serious disease affecting about 23 million people worldwide. Cardiac resynchronization therapy is used to treat patients suffering from symptomatic heart failure. However, 30% to 50% of patients have limited clinical benefit. One of the main causes is suboptimal placement of the left ventricular lead. Pacing in areas of myocardial scar correlates with poor clinical outcomes. Therefore precise knowledge of the individual patient's scar characteristics is critical for delivering tailored treatments capable of improving response rates. Current research methods for scar assessment either map information to an alternative non-anatomical coordinate system or they use the image coordinate system but lose critical information about scar extent and scar distribution. This paper proposes two interactive methods for visualizing relevant scar information. A 2-D slice based approach with a scar mask overlaid on a 16 segment heart model and a 3-D layered mesh visualization which allows physicians to scroll through layers of scar from endocardium to epicardium. These complementary methods enable physicians to evaluate scar location and transmurality during planning and guidance. Six physicians evaluated the proposed system by identifying target regions for lead placement. With the proposed method more target regions could be identified.

Solubility properties of siloxane polymers for chemical sensors

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

Grate, J.W.; Abraham, M.H.

1995-05-01

This paper discusses the factors governing the sorption of vapors by organic polymers. The principles have been applied in the past for designing and selecting polymers for acoustic wave sensors; however they apply equally well to sorption of vapors by polymers used on optical chemical sensors. A set of solvation parameters (a table is presented for various organic vapors) have been developed that describe the particular solubility properties of individual solute molecules; they are used in linear solvation energy relationships (LSER) that model the sorption process. LSER coefficients are tabulated for five polysiloxanes; so are individual interaction terms for eachmore » of the 5 polymers. Dispersion interactions play a major role in determining overall partition coefficients; the log L{sup 16} (gas-liquid partition coefficient of solute on hexadecane) value of vapors are important in determining overall sorption. For the detection of basic vapors such as organophosphates, a hydrogen-bond acidic polymers will be most effective at sorbing them. Currently, fiber optic sensors are being developed where the cladding serves as a sorbent layer to collect and concentrate analyte vapors, which will be detected and identified spectroscopically. These solubility models will be used to design the polymers for the cladding for particular vapors.« less

A quantitative study of the clustering of polycyclic aromatic hydrocarbons at high temperatures.

PubMed

Totton, Tim S; Misquitta, Alston J; Kraft, Markus

2012-03-28

The clustering of polycyclic aromatic hydrocarbon (PAH) molecules is investigated in the context of soot particle inception and growth using an isotropic potential developed from the benchmark PAHAP potential. This potential is used to estimate equilibrium constants of dimerisation for five representative PAH molecules based on a statistical mechanics model. Molecular dynamics simulations are also performed to study the clustering of homomolecular systems at a range of temperatures. The results from both sets of calculations demonstrate that at flame temperatures pyrene (C(16)H(10)) dimerisation cannot be a key step in soot particle formation and that much larger molecules (e.g. circumcoronene, C(54)H(18)) are required to form small clusters at flame temperatures. The importance of using accurate descriptions of the intermolecular interactions is demonstrated by comparing results to those calculated with a popular literature potential with an order of magnitude variation in the level of clustering observed. By using an accurate intermolecular potential we are able to show that physical binding of PAH molecules based on van der Waals interactions alone can only be a viable soot inception mechanism if concentrations of large PAH molecules are significantly higher than currently thought.

A mixed-methods observational study of human milk sharing communities on Facebook.

PubMed

Perrin, Maryanne Tigchelaar; Goodell, L Suzanne; Allen, Jonathan C; Fogleman, April

2014-04-01

The Food and Drug Administration discourages the casual sharing of human milk because of the risk of pathogen transmission. No information is currently available on the prevalence of this practice. The purpose of this mixed-methods observational study is to describe the size and activity of online milk sharing communities. Data for 3 months were extracted from nine public Facebook pages that facilitate the exchange of human milk. The numbers of participants, interactions, and comments were analyzed. We observed 954 individuals participating in milk sharing. The number of interactions per individual ranged from none to 16 (mean, 1.74 ± 1.65). Top reasons that participants requested milk included "lactation problems" (69.4%) and "child health problems" (48.5%). Nearly half of donors were offering 100 ounces or more, which is the minimum to be eligible to donate to nonprofit milk banks. Milk sharing networks in the United States are active, with thousands of individuals participating in the direct exchange of raw human milk. Public health issues include increasing the supply of pasteurized donor milk for fragile infants, increasing breastfeeding support, and helping milk sharing families appropriately manage risks.

Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders.

PubMed

Guastella, Adam J; Einfeld, Stewart L; Gray, Kylie M; Rinehart, Nicole J; Tonge, Bruce J; Lambert, Timothy J; Hickie, Ian B

2010-04-01

A diagnostic hallmark of autism spectrum disorders is a qualitative impairment in social communication and interaction. Deficits in the ability to recognize the emotions of others are believed to contribute to this. There is currently no effective treatment for these problems. In a double-blind, randomized, placebo-controlled, crossover design, we administered oxytocin nasal spray (18 or 24 IU) or a placebo to 16 male youth aged 12 to 19 who were diagnosed with Autistic or Asperger's Disorder. Participants then completed the Reading the Mind in the Eyes Task, a widely used and reliable test of emotion recognition. In comparison with placebo, oxytocin administration improved performance on the Reading the Mind in the Eyes Task. This effect was also shown when analysis was restricted to the younger participants aged 12 to 15 who received the lower dose. This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders. Findings suggest the potential of earlier intervention and further evaluation of oxytocin nasal spray as a treatment to improve social communication and interaction in young people with autism spectrum disorders. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Flexibility Considerations on the Hydrodynamic Loading on a Vertical Wedge Drop

NASA Astrophysics Data System (ADS)

Ren, Zhongshu; Wang, Zhaoyuan; Judge, Carolyn; Stern, Fred; Ikeda, Christine

2017-11-01

High-speed craft operating at in waves frequently become airborne and slam into the water surface. This fluid-structure interaction problem is important to understand in order to increase the operating envelope of these craft. The goals of the current work are to investigate both the hydrodynamic loads and the resulting structural response on a planing hull. A V-shaped wedge is dropped vertically into calm water. The hydrodynamic pressure is measured using pressure sensors at discrete points on the hull. Two hulls are studied: one is rigid and one is flexible. Predictions of the hydrodynamic loading are made using Wagner's theory, Vorus's theory, and simulations in CFDShip Iowa. These predictions assume the structure is completely rigid. These predictions of the pressure coefficient match well with the rigid hull, as expected. The spray root is tracked in the rigid experimental set and compared with the theoretical and computational models. The pressure coefficient measured on the flexible hull shows discrepancies with the predictions due to the fluid-structure interaction. These discrepancies are quantified and interpreted in light of the structural flexibility. Funding for this work is from the Office of Naval Research Grant Number N00014-16-1-3188.

Coping, social support, stigma, and gender difference among people living with HIV in Guangxi, China.

PubMed

Xiao, Zhiwen; Li, Xiaoming; Qiao, Shan; Zhou, Yuejiao; Shen, Zhiyong

2018-01-01

The current study examined whether gender, HIV-related stigma, social support, and the interaction between gender and social support are associated with coping responses among people living with HIV and AIDS (PLWHA) in Guangxi, China. A total of 2987 PLWHA in Guangxi participated from October 2012 to August 2013. Multivariate analysis of covariance was conducted with gender and social support as main factors in the model, and stigma and other variables as covariates. After controlling for demographic variables and stigma, there were significant main effects of emotional social support (F = 1.61, p < .001), functional social support (F = 1.67, p < .001), and informational social support (F = 3.67, p < .001) on various coping strategies. The interaction between gender and informational social support (F = 1.33, p < .05), internalized stigma (F = 37.03, p < .001) and perceived stigma (F = 9.16, p < .001) were associated with various coping strategies. Findings signify the importance of HIV-related stigma and social support differences in the coping strategies among PLWHA in Guangxi, China.

Synthesis of aryl pyrazole via Suzuki coupling reaction, in vitro mushroom tyrosinase enzyme inhibition assay and in silico comparative molecular docking analysis with Kojic acid.

PubMed

Channar, Pervaiz Ali; Saeed, Aamer; Larik, Fayaz Ali; Batool, Bakhtawar; Kalsoom, Saima; Hasan, M M; Erben, Mauricio F; El-Seedi, Hesham R; Ali, Musrat; Ashraf, Zaman

2018-04-30

Aryl pyrazoles are well recognized class of heterocyclic compounds found in several commercially available drugs. Owing to their significance in medicinal chemistry, in this current account we have synthesized a series of suitably substituted aryl pyrazole by employing Suzuki cross-coupling reaction. All compounds were evaluated for inhibition of mushroom tyrosinase enzyme both in vitro and in silico. Compound 3f (IC 50  = 1.568 ± 0.01 µM) showed relatively better potential compared to reference kojic acid (IC 50  = 16.051 ± 1.27 µM). A comparative docking studies showed that compound 3f have maximum binding affinity against mushroom tyrosinase (PDBID: 2Y9X) with binding energy value (-6.90 kcal/mol) as compared to Kojic acid. The 4-methoxy group in compound 3f shows 100% interaction with Cu. Compound 3f displayed hydrogen binding interaction with His61 and His94 at distance of 1.71 and 1.74 Å which might be responsible for higher activity compared to Kojic acid. Copyright © 2018 Elsevier Inc. All rights reserved.

PAIN INTENSITY MODERATES THE RELATIONSHIP BETWEEN AGE AND PAIN INTERFERENCE IN CHRONIC OROFACIAL PAIN PATIENTS

PubMed Central

Boggero, Ian A.; Geiger, Paul J.; Segerstrom, Suzanne C.; Carlson, Charles R.

2015-01-01

Background/Study Context Chronic pain is associated with increased interference in daily functioning that becomes more pronounced as pain intensity increases. Based on previous research showing that older adults maintain well-being in the face of pain as well as or better than their younger counterparts, the current study examined the interaction of age and pain intensity on interference in a sample of chronic orofacial pain patients. Methods Data were obtained from the records of 508 chronic orofacial pain patients being seen for an initial evaluation from 2008 to 2012. Collected data included age (range: 18–78) and self-reported measures of pain intensity and pain interference. Bivariate correlations and regression models were used to assess for statistical interactions. Results Regression analyses revealed that pain intensity positively predicted pain interference (R2 = .35, B = 10.40, SE = 0.62, t(507) = 16.70, p < .001). A significant interaction supported the primary hypothesis that aging was associated with reduced interference at high levels of pain intensity (ΔR2 = .01, B = −1.31, SE = 0.63, t(505) = −2.90, p = .04). Conclusion At high levels of pain intensity, interference decreased with age, although the age by pain intensity interaction effect was small. This evidence converges with aging theories, including socioemotional selectivity theory, which posits that as people age, they become more motivated to maximize positive emotions and minimize negative ones. The results highlight the importance of studying the mechanisms older adults use to successfully cope with pain. PMID:26214102

Mutations in M2 alter the selectivity of the mouse nicotinic acetylcholine receptor for organic and alkali metal cations

PubMed Central

1992-01-01

We measured the permeability ratios (PX/PNa) of 3 wild-type, 1 hybrid, 2 subunit-deficient, and 22 mutant nicotinic receptors expressed in Xenopus oocytes for alkali metal and organic cations using shifts in the bi-ionic reversal potential of the macroscopic current. Mutations at three positions (2', 6', 10') in M2 affected ion selectivity. Mutations at position 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) near the intracellular end of M2 changed the organic cation permeability ratios as much as twofold and reduced PCs/PNa and PK/PNa by 16-18%. Mutations at positions 6' and 10' increased the glycine ethyl ester/Na+ and glycine methyl ester/Na+ permeability ratios. Two subunit alterations also affected selectivity: omission of the delta subunit reduced PCs/PNa by 16%, and substitution of Xenopus delta for mouse delta increased Pguanidinium/PNa more than twofold and reduced PCs/PNa by 34% and PLi/PNa by 20%. The wild-type mouse receptor displayed a surprising interaction with the primary ammonium cations; relative permeability peaked at a chain length equal to four carbons. Analysis of the organic permeability ratios for the wild-type mouse receptor shows that (a) the diameter of the narrowest part of the pore is 8.4 A; (b) the mouse receptor departs significantly from size selectivity for monovalent organic cations; and (c) lowering the temperature reduces Pguanidinium/PNa by 38% and Pbutylammonium/PNa more than twofold. The results reinforce present views that positions -1' and 2' are the narrowest part of the pore and suggest that positions 6' and 10' align some permeant organic cations in the pore in an interaction similar to that with channel blocker, QX-222. PMID:1431803

HuMiChip: Development of a Functional Gene Array for the Study of Human Microbiomes

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

Tu, Q.; Deng, Ye; Lin, Lu

Microbiomes play very important roles in terms of nutrition, health and disease by interacting with their hosts. Based on sequence data currently available in public domains, we have developed a functional gene array to monitor both organismal and functional gene profiles of normal microbiota in human and mouse hosts, and such an array is called human and mouse microbiota array, HMM-Chip. First, seed sequences were identified from KEGG databases, and used to construct a seed database (seedDB) containing 136 gene families in 19 metabolic pathways closely related to human and mouse microbiomes. Second, a mother database (motherDB) was constructed withmore » 81 genomes of bacterial strains with 54 from gut and 27 from oral environments, and 16 metagenomes, and used for selection of genes and probe design. Gene prediction was performed by Glimmer3 for bacterial genomes, and by the Metagene program for metagenomes. In total, 228,240 and 801,599 genes were identified for bacterial genomes and metagenomes, respectively. Then the motherDB was searched against the seedDB using the HMMer program, and gene sequences in the motherDB that were highly homologous with seed sequences in the seedDB were used for probe design by the CommOligo software. Different degrees of specific probes, including gene-specific, inclusive and exclusive group-specific probes were selected. All candidate probes were checked against the motherDB and NCBI databases for specificity. Finally, 7,763 probes covering 91.2percent (12,601 out of 13,814) HMMer confirmed sequences from 75 bacterial genomes and 16 metagenomes were selected. This developed HMM-Chip is able to detect the diversity and abundance of functional genes, the gene expression of microbial communities, and potentially, the interactions of microorganisms and their hosts.« less

IRS Spectral Maps of Photoevaporative Columns in M16, Carina, and the Galactic Center

NASA Astrophysics Data System (ADS)

Cotera, Angela; Healy, Kevin; Hester, Jeff; Sellgren, Kris; Simpson, Janet; Stolovy, Susan

2008-03-01

Photoevaporated columns of dust and gas - also called elephant trunks, pillars or fingers - are found in the periphery of H II regions, and have been observed within the Galaxy, the SMC and the LMC. These features are sites of current star formation, but the question remains whether the columns persist because stars formed in the denser regions prior to interactions with the UV radiation and stellar winds of nearby massive stars, or because of core collapse resulting from these interactions. Mapping the distribution of the physical states of the dust and gas in these columns is a necessary step towards understanding the possible star formation mechanisms within these dynamic objects. We propose to obtain IRS spectral maps of columns within M 16, the Carina nebula, and the Galactic center (GC) to understand the effects on these pillars from different stellar populations and initial conditions, and to better understand star formation in the GC. Within the spectral range of the high resolution IRS modes (9.9-37.2 micron) there are a wealth of molecular, atomic and PAH emission lines that will enable us to determine the excitation state, dust and gas temperatures, and probe the shock characteristics within the columns. Using the IRS spectral mapping mode, in conjunction with the CUBISM tool and the CLOUDY H II region model code, we will be able to construct detailed maps of the accessible emission lines and derived parameters for each column. IRS mapping of elephant trunks has not been done to date, yet provides a wealth of information unobtainable for the foreseeable future once Cycle 5 is completed.

Mental distress predicts divorce over 16 years: the HUNT study.

PubMed

Idstad, Mariann; Torvik, Fartein Ask; Borren, Ingrid; Rognmo, Kamilla; Røysamb, Espen; Tambs, Kristian

2015-04-01

The association between mental distress and divorce is well established in the literature. Explanations are commonly classified within two different frameworks; social selection (mentally distressed people are selected out of marriage) and social causation (divorce causes mental distress). Despite a relatively large body of literature on this subject, selection effects are somewhat less studied, and research based on data from both spouses is scarce. The purpose of the present study is to investigate selection effects both at the individual level and the couple level. The current study is based on couple-level data from a Norwegian representative sample including 20,233 couples. Long-term selection effects were tested for by means of Cox proportional hazard models, using mental distress in both partners at baseline as predictors of divorce the next 16 years. Three identical sets of analyses were run. The first included the total sample, whereas the second and third excluded couples who divorced within the first 4 or 8 years after baseline, respectively. An interaction term between mental distress in husband and in wife was specified and tested. Hazard of divorce was significantly higher in couples with one mentally distressed partner than in couples with no mental distress in all analyses. There was also a significant interaction effect showing that the hazard of divorce for couples with two mentally distressed partners was higher than for couples with one mentally distressed partner, but lower than what could be expected from the combined main effects of two mentally distressed partners. Our results suggest that mentally distressed individuals are selected out of marriage. We also found support for a couple-level effect in which spouse similarity in mental distress to a certain degree seems to protect against divorce.

Is the dissociation of coronene in stellar winds a source of molecular hydrogen? application to the HD 44179 nebula

NASA Astrophysics Data System (ADS)

Champeaux, J.-P.; Moretto-Capelle, P.; Cafarelli, P.; Deville, C.; Sence, M.; Casta, R.

2014-06-01

The physical interactions of polycyclic aromatic hydrocarbons (PAHs) with stellar particular radiation are key to understanding the life cycle of PAHs, their abundance and their role in the complex astrochemistry of the interstellar medium. In this context, we present experimental results on the ionization/fragmentation of isolated coronene by a 100-keV proton, reproducing interactions between stellar winds and PAH molecules in the star's environment. In particular, we show, without ambiguity, that such ionization/fragmentation induces intense dehydrogenation processes for which the loss of even numbers of hydrogen atoms and the detection of CH_2+ cations as a possible H2 precursor strongly suggest the formation of H2 neutral molecules along a scenario revealed by a quantum chemical calculation. We have evaluated the H2 emission cross-section from the coronene/proton interaction at 100 and 1.6 keV to be 2.97 × 10-16 and 3.3 × 10-16 cm2, respectively. A qualitative discussion on the formation rate of H2 in the HD 44179 Red Rectangle (RR) nebula leads to the conclusion that such processes could be very efficient, especially inside planetary nebulae rich in PAH molecules interacting with high proton mass-loss rate stars (such as post-asymptotic giant branch stars) or high velocity jets produced by an accretion disc.

Development of a Sodium Lidar for Space-Borne Missions

NASA Astrophysics Data System (ADS)

Janches, D.; Krainak, M. A.; Yu, A. W.; Jones, S.; Chen, J. R.

2015-12-01

We are currently developing laser and electro-optic technologies to remotely measure Sodium (Na) by adapting existing lidar technology with space flight heritage to study the composition and dynamics of Earth's mesosphere based on a spaceborne instrument that will measure the mesospheric Na layer. There is a pressing need in the Ionosphere - Thermosphere - Mesosphere (ITM) community for high-resolution measurements that can characterize the effect of small-scale dynamics (i.e. Gravity Waves with wavelengths smaller than a few hundred km) in the Mesosphere-Lower-Termosphere (MLT) on a global basis. This is compelling because they are believed to be the dominant contributors to momentum transport and deposition in the MLT, which largely drive the global circulation and thermal structure and interactions with the tides and planetary waves in this region. A nadir-pointing spaceborne Na Doppler resonance fluorescence LIDAR on board of the International Space Station (ISS) will essentially make high-resolution, in time and space, Na density, temperature and vertical wind measurements, from 75-115 km (MLT region). Our instrument concept consisted of a high-energy laser transmitter at 589 nm and highly sensitive photon counting detector that allows for range-resolved atmospheric-sodium-temperature profiles. The atmospheric temperature is deduced from the linewidth of the resonant fluorescence from the atomic sodium vapor D2 line as measured by our tunable laser. We are currently developing a high power energy laser that allows for some day time sodium lidar observations with the help of a narrow bandpass filter based on etalon or atomic sodium Faraday filter with ~5 to 10 pm optical bandwidth. The current baseline detector for the lidar instrument is a 16-channel Photomultiplier Tube with receiver electronics that has been space-qualified for the ICESat-2/ATLAS mission. Our technique uses the 16-channels as a photon-number-resolving "single" detector to provide the required full-spectroscopic sodium lineshape waveform for recovering Mesospheric temperature profiles. In this paper, we will describe our instrument concept for a future Heliophysics space mission based on board of the ISS as well as show current progress results.

Electronic properties of the interface between hexadecafluoro copper phthalocyanine and unsubstituted copper phthalocyanine films

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

Komolov, A. S., E-mail: akomolov07@ya.ru; Lazneva, E. F.; Pshenichnyuk, S. A.

2013-07-15

The formation of an interface during the deposition of unsubstituted copper phthalocyanine (CuPc) films on the surface of hexadecafluoro copper phthalocyanine (F{sub 16}-CuPc) films is studied. An incident low-energy electron beam with energies from 0 to 25 eV is used to test the surface under study according to the very-low-energy electron-diffraction technique (VLEED) in the mode of total current spectroscopy. For F{sub 16}-CuPc films, the structure of the maxima in the total current spectra and its main differences from the structure of the maxima for the CuPc film are determined in the energy range from 5 to 15 eV abovemore » the Fermi level. The differences in the structure of vacant electron orbitals for CuPc and F{sub 16}-CuPc are also revealed using density functional theory calculations. As a result of an analysis of variations in the intensities of the total current spectra of the CuPc and F{sub 16}-CuPc films, it is assumed that an intermediate layer up to 1 nm thick appears during the formation of an interface between these films, which is characterized by a spread of the features in the total current spectrum. The height, width, and change in the work function are determined for the studied F{sub 16}-CuPc/NuPc interface barrier. A decrease in the level of vacuum by 0.7 eV occurs in the boundary region, which corresponds to electron density transfer from the CuPc film toward the F{sub 16}-CuPc substrate.« less

Magnetic field manipulation of spin current in a single-molecule magnet tunnel junction with two-electron Coulomb interaction

NASA Astrophysics Data System (ADS)

Zhang, Chao; Yao, Hui; Nie, Yi-Hang; Liang, Jiu-Qing; Niu, Peng-Bin

2018-04-01

In this work, we study the generation of spin-current in a single-molecule magnet (SMM) tunnel junction with Coulomb interaction of transport electrons and external magnetic field. In the absence of field the spin-up and -down currents are symmetric with respect to the initial polarizations of molecule. The existence of magnetic field breaks the time-reversal symmetry, which leads to unsymmetrical spin currents of parallel and antiparallel polarizations. Both the amplitude and polarization direction of spin current can be controlled by the applied magnetic field. Particularly when the magnetic field increases to a certain value the spin-current with antiparallel polarization is reversed along with the magnetization reversal of the SMM. The two-electron occupation indeed enhances the transport current compared with the single-electron process. However the increase of Coulomb interaction results in the suppression of spin-current amplitude at the electron-hole symmetry point. We propose a scheme to compensate the suppression with the magnetic field.

TASEP of interacting particles of arbitrary size

NASA Astrophysics Data System (ADS)

Narasimhan, S. L.; Baumgaertner, A.

2017-10-01

A mean-field description of the stationary state behaviour of interacting k-mers performing totally asymmetric exclusion processes (TASEP) on an open lattice segment is presented employing the discrete Takahashi formalism. It is shown how the maximal current and the phase diagram, including triple-points, depend on the strength of repulsive and attractive interactions. We compare the mean-field results with Monte Carlo simulation of three types interacting k-mers: monomers, dimers and trimers. (a) We find that the Takahashi estimates of the maximal current agree quantitatively with those of the Monte Carlo simulation in the absence of interaction as well as in both the the attractive and the strongly repulsive regimes. However, theory and Monte Carlo results disagree in the range of weak repulsion, where the Takahashi estimates of the maximal current show a monotonic behaviour, whereas the Monte Carlo data show a peaking behaviour. It is argued that the peaking of the maximal current is due to a correlated motion of the particles. In the limit of very strong repulsion the theory predicts a universal behavior: th maximal currents of k-mers correspond to that of non-interacting (k+1) -mers; (b) Monte Carlo estimates of the triple-points for monomers, dimers and trimers show an interesting general behaviour : (i) the phase boundaries α * and β* for entry and exit current, respectively, as function of interaction strengths show maxima for α* whereas β * exhibit minima at the same strength; (ii) in the attractive regime, however, the trend is reversed (β * > α * ). The Takahashi estimates of the triple-point for monomers show a similar trend as the Monte Carlo data except for the peaking of α * ; for dimers and trimers, however, the Takahashi estimates show an opposite trend as compared to the Monte Carlo data.

Biological Characterization of an Improved Pyrrole-Based Colchicine Site Agent Identified through Structure-Based Design

PubMed Central

Rohena, Cristina C.; Telang, Nakul S.; Da, Chenxiao; Risinger, April L.; Sikorski, James A.; Kellogg, Glen E.; Gupton, John T.

2016-01-01

A refined model of the colchicine site on tubulin was used to design an improved analog of the pyrrole parent compound, JG-03-14. The optimized compound, NT-7-16, was evaluated in biological assays that confirm that it has potent activities as a new colchicine site microtubule depolymerizer. NT-7-16 exhibits antiproliferative and cytotoxic activities against multiple cancer cell lines, with IC50 values of 10–16 nM, and it is able to overcome drug resistance mediated by the expression of P-glycoprotein and the βIII isotype of tubulin. NT-7-16 initiated the concentration-dependent loss of cellular microtubules and caused the formation of abnormal mitotic spindles, leading to mitotic accumulation. The direct interaction of NT-7-16 with purified tubulin was confirmed, and it was more potent than combretastatin A-4 in these assays. Binding studies verified that NT-7-16 binds to tubulin within the colchicine site. The antitumor effects of NT-7-16 were evaluated in an MDA-MB-435 xenograft model and it had excellent activity at concentrations that were not toxic. A second compound, NT-9-21, which contains dichloro moieties in place of the 3,5-dibromo substituents of NT-7-16, had a poorer fit within the colchicine site as predicted by modeling and the Hydropathic INTeractions score. Biological evaluations showed that NT-9-21 has 10-fold lower potency than NT-7-16, confirming the modeling predictions. These studies highlight the value of the refined colchicine-site model and identify a new pyrrole-based colchicine-site agent with potent in vitro activities and promising in vivo antitumor actions. PMID:26655304

Exponential Characteristic Spatial Quadrature for Discrete Ordinates Neutral Particle Transport in Slab Geometry

DTIC Science & Technology

1992-03-01

left bdy = 0 vacuum current incident at left boundary = I type of current incident at left bdy = 0 isotropic surface Src region# cR SigmaR SourceR nc...0 type of current incident at left bdy = 0 isotropic surface Src region# cR SigmaR SourceR nc Right Bdy 1 0.5000 .3OD+00 0.0000D+00 256. 16.0000 2... SigmaR SourceR nc Right Bdy 1 0.1000 1.0000D+00 0.0000D+00 256. 16.0000 2 0.9500 1.0(OOD+00 1.0000D+00 256. 32.0000 type of right bdy = 0 vacuum current

A Review: The Current In Vivo Models for the Discovery and Utility of New Anti-leishmanial Drugs Targeting Cutaneous Leishmaniasis

PubMed Central

Mears, Emily Rose; Modabber, Farrokh; Don, Robert; Johnson, George E.

2015-01-01

The current in vivo models for the utility and discovery of new potential anti-leishmanial drugs targeting Cutaneous Leishmaniasis (CL) differ vastly in their immunological responses to the disease and clinical presentation of symptoms. Animal models that show similarities to the human form of CL after infection with Leishmania should be more representative as to the effect of the parasite within a human. Thus, these models are used to evaluate the efficacy of new anti-leishmanial compounds before human clinical trials. Current animal models aim to investigate (i) host–parasite interactions, (ii) pathogenesis, (iii) biochemical changes/pathways, (iv) in vivo maintenance of parasites, and (v) clinical evaluation of drug candidates. This review focuses on the trends of infection observed between Leishmania parasites, the predictability of different strains, and the determination of parasite load. These factors were used to investigate the overall effectiveness of the current animal models. The main aim was to assess the efficacy and limitations of the various CL models and their potential for drug discovery and evaluation. In conclusion, we found that the following models are the most suitable for the assessment of anti-leishmanial drugs: L. major–C57BL/6 mice (or–vervet monkey, or–rhesus monkeys), L. tropica–CsS-16 mice, L. amazonensis–CBA mice, L. braziliensis–golden hamster (or–rhesus monkey). We also provide in-depth guidance for which models are not suitable for these investigations. PMID:26334763

Cyanoacrylate tissue adhesives - effective securement technique for intravascular catheters: in vitro testing of safety and feasibility.

PubMed

Simonova, G; Rickard, C M; Dunster, K R; Smyth, D J; McMillan, D; Fraser, J F

2012-05-01

Partial or complete dislodgement of intravascular catheters remains a significant problem in hospitals despite current securement methods. Cyanoacrylate tissue adhesives (TA) are used to close skin wounds as an alternative to sutures. These adhesives have high mechanical strength and can remain in situ for several days. This study investigated in vitro use of TAs in securing intravascular catheters (IVC). We compared two adhesives for interaction with IVC material, comparing skin glues with current securement methods in terms of their ability to prevent IVC dislodgement and inhibit microbial growth. Two TAs (Dermabond, Ethicon Inc. and Histoacryl, B. Braun) and three removal agents (Remove™, paraffin and acetone) were tested for interaction with IVC material by use of tensile testing. TAs were also compared against two polyurethane (standard and bordered) dressings (Tegaderm™ 1624 and 1633, 3M Australia Pty Ltd) and an external stabilisation device (Statlock, Bard Medical, Covington) against control (unsecured IVCs) for ability to prevent pull-out of 16 G peripheral IVCs from newborn fresh porcine skin. Agar media containing pH-sensitive dye was used to assess antimicrobial properties of TAs and polyurethane dressings to inhibit growth of Staphylococcus aureus and Staphylococcus epidermidis. Neither TA weakened the IVCs (P >0.05). Of removal agents, only acetone was associated with a significant decrease in IVC strength (P <0.05). Both TAs and Statlock significantly increased the pull-out force (P <0.01). TA was quick and easy to apply to IVCs, with no irritation or skin damage noted on removal and no bacterial colony growth under either TA.

Intestinal microbiota in functional bowel disorders: a Rome foundation report

PubMed Central

Barbara, Giovanni; Flint, Harry J; Spiegel, Brennan M R; Spiller, Robin C; Vanner, Stephen; Verdu, Elena F; Whorwell, Peter J; Zoetendal, Erwin G

2013-01-01

It is increasingly perceived that gut host–microbial interactions are important elements in the pathogenesis of functional gastrointestinal disorders (FGID). The most convincing evidence to date is the finding that functional dyspepsia and irritable bowel syndrome (IBS) may develop in predisposed individuals following a bout of infectious gastroenteritis. There has been a great deal of interest in the potential clinical and therapeutic implications of small intestinal bacterial overgrowth in IBS. However, this theory has generated much debate because the evidence is largely based on breath tests which have not been validated. The introduction of culture-independent molecular techniques provides a major advancement in our understanding of the microbial community in FGID. Results from 16S rRNA-based microbiota profiling approaches demonstrate both quantitative and qualitative changes of mucosal and faecal gut microbiota, particularly in IBS. Investigators are also starting to measure host–microbial interactions in IBS. The current working hypothesis is that abnormal microbiota activate mucosal innate immune responses which increase epithelial permeability, activate nociceptive sensory pathways and dysregulate the enteric nervous system. While we await important insights in this field, the microbiota is already a therapeutic target. Existing controlled trials of dietary manipulation, prebiotics, probiotics, synbiotics and non-absorbable antibiotics are promising, although most are limited by suboptimal design and small sample size. In this article, the authors provide a critical review of current hypotheses regarding the pathogenetic involvement of microbiota in FGID and evaluate the results of microbiota-directed interventions. The authors also provide clinical guidance on modulation of gut microbiota in IBS. PMID:22730468

Climate change threatens endangered plant species by stronger and interacting water-related stresses

NASA Astrophysics Data System (ADS)

Bartholomeus, Ruud P.; Witte, Jan-Philip M.; van Bodegom, Peter M.; van Dam, Jos C.; Aerts, Rien

2011-12-01

Atmospheric CO2-concentration, temperature and rainfall variability are all expected to increase in the near future. The resulting increased dynamics of soil moisture contents, together with increased plant physiological demands for both oxygen and water, will lead to an increased occurrence of wet and dry extremes of plant stresses, i.e., of oxygen and drought stress, respectively, alone and in interaction. The use of indirect environmental variables in previous studies and a focus on individual stresses rather than their combined effects has hampered understanding of the causal impact of climate change on plant species composition through changes in abiotic site conditions. Here, we use process-based simulations of oxygen and drought stresses in conjunction with a downscaled national version of IPCC scenarios in order to show that these stresses will increase (on average by ˜20% at sites where both stresses occur) in a warmer and more variable future (2050) climate. These two types of stresses will increasingly coincide, i.e. both stresses will occur more often (but not at the same time) within a single vegetation plot. We further show that this increased coincidence of water-related stresses will negatively affect the future occurrence of currently endangered plant species (causing a reduction of ˜16%), while apparently no such decrease will occur among common species. Individual stresses did not appear to affect the occurrence of endangered plant species. Consequently, our study demonstrates that species that are already threatened under the current climate will suffer most from the effects of climate change.

Current-driven ion-acoustic and potential-relaxation instabilities excited in plasma plume during electron beam welding

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

Trushnikov, D. N., E-mail: trdimitr@yandex.ru; Mladenov, G. M., E-mail: gmmladenov@abv.bg; Koleva, E. G., E-mail: eligeorg@abv.bg

Many papers have sought correlations between the parameters of secondary particles generated above the beam/work piece interaction zone, dynamics of processes in the keyhole, and technological processes. Low- and high-frequency oscillations of the current, collected by plasma have been observed above the welding zone during electron beam welding. Low-frequency oscillations of secondary signals are related to capillary instabilities of the keyhole, however; the physical mechanisms responsible for the high-frequency oscillations (>10 kHz) of the collected current are not fully understood. This paper shows that peak frequencies in the spectra of the collected high-frequency signal are dependent on the reciprocal distancemore » between the welding zone and collector electrode. From the relationship between current harmonics frequency and distance of the collector/welding zone, it can be estimated that the draft velocity of electrons or phase velocity of excited waves is about 1600 m/s. The dispersion relation with the properties of ion-acoustic waves is related to electron temperature 10 000 K, ion temperature 2 400 K and plasma density 10{sup 16} m{sup −3}, which is analogues to the parameters of potential-relaxation instabilities, observed in similar conditions. The estimated critical density of the transported current for creating the anomalous resistance state of plasma is of the order of 3 A·m{sup −2}, i.e. 8 mA for a 3–10 cm{sup 2} collector electrode. Thus, it is assumed that the observed high-frequency oscillations of the current collected by the positive collector electrode are caused by relaxation processes in the plasma plume above the welding zone, and not a direct demonstration of oscillations in the keyhole.« less

Crystal structure of 2-meth-oxy-2-[(4-meth-oxy-phen-yl)sulfan-yl]-1-phenyl-ethanone.

PubMed

Caracelli, Ignez; Olivato, Paulo R; Traesel, Henrique J; Valença, Jéssica; Rodrigues, Daniel N S; Tiekink, Edward R T

2015-09-01

In the title β-thio-carbonyl compound, C16H16O3S, the adjacent meth-oxy and carbonyl O atoms are synperiplanar [the O-C-C-O torsion angle is 19.8 (4)°] and are separated by 2.582 (3) Å. The dihedral angle between the rings is 40.11 (16)°, and the meth-oxy group is coplanar with the benzene ring to which it is connected [the C-C-O-C torsion angle is 179.1 (3)°]. The most notable feature of the crystal packing is the formation of methine and methyl C-H⋯O(carbon-yl) inter-actions that lead to a supra-molecular chain with a zigzag topology along the c axis. Chains pack with no specific inter-molecular inter-actions between them.

Amicoumacin A inhibits translation by stabilizing mRNA interaction with the ribosome

PubMed Central

Polikanov, Yury S.; Osterman, Ilya A.; Szal, Teresa; Tashlitsky, Vadim N.; Serebryakova, Marina V.; Kusochek, Pavel; Bulkley, David; Malanicheva, Irina A.; Efimenko, Tatyana A.; Efremenkova, Olga V.; Konevega, Andrey L.; Shaw, Karen J.; Bogdanov, Alexey A.; Rodnina, Marina V.; Dontsova, Olga A.; Mankin, Alexander S.; Steitz, Thomas A.; Sergiev, Petr V.

2014-01-01

SUMMARY We demonstrate that the antibiotic amicoumacin A (AMI) whose cellular target was unknown, is a potent inhibitor of protein synthesis. Resistance mutations in helix 24 of the 16S rRNA mapped the AMI binding site to the small ribosomal subunit. The crystal structure of bacterial ribosome in complex with AMI solved at 2.4 Å resolution revealed that the antibiotic makes contacts with universally conserved nucleotides of 16S rRNA in the E site and the mRNA backbone. Simultaneous interactions of AMI with 16S rRNA and mRNA and the in vivo experimental evidence suggest that it may inhibit the progression of the ribosome along mRNA. Consistent with this proposal, binding of AMI interferes with translocation in vitro. The inhibitory action of AMI can be partly compensated by mutations in the translation elongation factor G. PMID:25306919

The Interactive Influences of Friend Deviance and Reward Dominance on the Development of Externalizing Behavior During Middle Adolescence

PubMed Central

Bates, John E.; Newman, Joseph P.; Dodge, Kenneth A.; Pettit, Gregory S.

2009-01-01

This study investigated the interactive effects of friend deviance and reward dominance on the development of externalizing behavior of adolescents in the Child Development Project. Reward dominance was assessed at age 16 by performance on a computer-presented card-playing game in which participants had the choice of either continuing or discontinuing the game as the likelihood of reward decreased and the likelihood of punishment increased. At ages 14 and 16, friend deviance and externalizing behavior were assessed through self-report. As expected, based on motivational balance and response modulation theories, path analysis revealed that age 14 friend deviance predicted age 16 externalizing behavior controlling for age 14 externalizing behavior. Reward dominance was a significant moderator of the relationship between friend deviance and externalizing behavior. The contributions of deviant friends to the development of externalizing behavior were enhanced by adolescents' reward dominance. PMID:16823636

The interactive influences of friend deviance and reward dominance on the development of externalizing behavior during middle adolescence.

PubMed

Goodnight, Jackson A; Bates, John E; Newman, Joseph P; Dodge, Kenneth A; Pettit, Gregory S

2006-10-01

This study investigated the interactive effects of friend deviance and reward dominance on the development of externalizing behavior of adolescents in the Child Development Project. Reward dominance was assessed at age 16 by performance on a computer-presented card-playing game in which participants had the choice of either continuing or discontinuing the game as the likelihood of reward decreased and the likelihood of punishment increased. At ages 14 and 16, friend deviance and externalizing behavior were assessed through self-report. As expected, based on motivational balance and response modulation theories, path analysis revealed that age 14 friend deviance predicted age 16 externalizing behavior controlling for age 14 externalizing behavior. Reward dominance was a significant moderator of the relationship between friend deviance and externalizing behavior. The contributions of deviant friends to the development of externalizing behavior were enhanced by adolescents' reward dominance.

Testing Hadronic Interactions at Ultrahigh Energies with Air Showers Measured by the Pierre Auger Observatory

NASA Astrophysics Data System (ADS)

Aab, A.; Abreu, P.; Aglietta, M.; Ahn, E. J.; Al Samarai, I.; Albuquerque, I. F. M.; Allekotte, I.; Allen, J. D.; Allison, P.; Almela, A.; Alvarez Castillo, J.; Alvarez-Muñiz, J.; Ambrosio, M.; Anastasi, G. A.; Anchordoqui, L.; Andrada, B.; Andringa, S.; Aramo, C.; Arqueros, F.; Arsene, N.; Asorey, H.; Assis, P.; Aublin, J.; Avila, G.; Badescu, A. M.; Baus, C.; Beatty, J. J.; Becker, K. H.; Bellido, J. A.; Berat, C.; Bertaina, M. E.; Bertou, X.; Biermann, P. L.; Billoir, P.; Biteau, J.; Blaess, S. G.; Blanco, A.; Blazek, J.; Bleve, C.; Blümer, H.; Boháčová, M.; Boncioli, D.; Bonifazi, C.; Borodai, N.; Botti, A. M.; Brack, J.; Brancus, I.; Bretz, T.; Bridgeman, A.; Briechle, F. L.; Buchholz, P.; Bueno, A.; Buitink, S.; Buscemi, M.; Caballero-Mora, K. S.; Caccianiga, B.; Caccianiga, L.; Cancio, A.; Canfora, F.; Caramete, L.; Caruso, R.; Castellina, A.; Cataldi, G.; Cazon, L.; Cester, R.; Chavez, A. G.; Chiavassa, A.; Chinellato, J. A.; Chirinos Diaz, J. C.; Chudoba, J.; Clay, R. W.; Colalillo, R.; Coleman, A.; Collica, L.; Coluccia, M. R.; Conceição, R.; Contreras, F.; Cooper, M. J.; Coutu, S.; Covault, C. E.; Cronin, J.; Dallier, R.; D'Amico, S.; Daniel, B.; Dasso, S.; Daumiller, K.; Dawson, B. R.; de Almeida, R. M.; de Jong, S. J.; De Mauro, G.; de Mello Neto, J. R. T.; De Mitri, I.; de Oliveira, J.; de Souza, V.; Debatin, J.; del Peral, L.; Deligny, O.; Dhital, N.; Di Giulio, C.; Di Matteo, A.; Díaz Castro, M. L.; Diogo, F.; Dobrigkeit, C.; D'Olivo, J. C.; Dorofeev, A.; dos Anjos, R. C.; Dova, M. T.; Dundovic, A.; Ebr, J.; Engel, R.; Erdmann, M.; Erfani, M.; Escobar, C. O.; Espadanal, J.; Etchegoyen, A.; Falcke, H.; Fang, K.; Farrar, G. R.; Fauth, A. C.; Fazzini, N.; Ferguson, A. P.; Fick, B.; Figueira, J. M.; Filevich, A.; Filipčič, A.; Fratu, O.; Freire, M. M.; Fujii, T.; Fuster, A.; Gallo, F.; García, B.; Garcia-Pinto, D.; Gate, F.; Gemmeke, H.; Gherghel-Lascu, A.; Ghia, P. L.; Giaccari, U.; Giammarchi, M.; Giller, M.; Głas, D.; Glaser, C.; Glass, H.; Golup, G.; Gómez Berisso, M.; Gómez Vitale, P. F.; González, N.; Gookin, B.; Gordon, J.; Gorgi, A.; Gorham, P.; Gouffon, P.; Griffith, N.; Grillo, A. F.; Grubb, T. D.; Guarino, F.; Guedes, G. P.; Hampel, M. R.; Hansen, P.; Harari, D.; Harrison, T. A.; Harton, J. L.; Hasankiadeh, Q.; Haungs, A.; Hebbeker, T.; Heck, D.; Heimann, P.; Herve, A. E.; Hill, G. C.; Hojvat, C.; Hollon, N.; Holt, E.; Homola, P.; Hörandel, J. R.; Horvath, P.; Hrabovský, M.; Huege, T.; Hulsman, J.; Insolia, A.; Isar, P. G.; Jandt, I.; Jansen, S.; Jarne, C.; Johnsen, J. A.; Josebachuili, M.; Kääpä, A.; Kambeitz, O.; Kampert, K. H.; Kasper, P.; Katkov, I.; Keilhauer, B.; Kemp, E.; Kieckhafer, R. M.; Klages, H. O.; Kleifges, M.; Kleinfeller, J.; Krause, R.; Krohm, N.; Kuempel, D.; Kukec Mezek, G.; Kunka, N.; Kuotb Awad, A.; LaHurd, D.; Latronico, L.; Lauscher, M.; Lautridou, P.; Lebrun, P.; Legumina, R.; Leigui de Oliveira, M. A.; Letessier-Selvon, A.; Lhenry-Yvon, I.; Link, K.; Lopes, L.; López, R.; López Casado, A.; Lucero, A.; Malacari, M.; Mallamaci, M.; Mandat, D.; Mantsch, P.; Mariazzi, A. G.; Marin, V.; Mariş, I. C.; Marsella, G.; Martello, D.; Martinez, H.; Martínez Bravo, O.; Masías Meza, J. J.; Mathes, H. J.; Mathys, S.; Matthews, J.; Matthews, J. A. J.; Matthiae, G.; Maurizio, D.; Mayotte, E.; Mazur, P. O.; Medina, C.; Medina-Tanco, G.; Mello, V. B. B.; Melo, D.; Menshikov, A.; Messina, S.; Micheletti, M. I.; Middendorf, L.; Minaya, I. A.; Miramonti, L.; Mitrica, B.; Molina-Bueno, L.; Mollerach, S.; Montanet, F.; Morello, C.; Mostafá, M.; Moura, C. A.; Müller, G.; Muller, M. A.; Müller, S.; Naranjo, I.; Navas, S.; Necesal, P.; Nellen, L.; Nelles, A.; Neuser, J.; Nguyen, P. H.; Niculescu-Oglinzanu, M.; Niechciol, M.; Niemietz, L.; Niggemann, T.; Nitz, D.; Nosek, D.; Novotny, V.; Nožka, H.; Núñez, L. A.; Ochilo, L.; Oikonomou, F.; Olinto, A.; Pakk Selmi-Dei, D.; Palatka, M.; Pallotta, J.; Papenbreer, P.; Parente, G.; Parra, A.; Paul, T.; Pech, M.; Pedreira, F.; Pekala, J.; Pelayo, R.; Peña-Rodriguez, J.; Pepe, I. M.; Pereira, L. A. S.; Perrone, L.; Petermann, E.; Peters, C.; Petrera, S.; Phuntsok, J.; Piegaia, R.; Pierog, T.; Pieroni, P.; Pimenta, M.; Pirronello, V.; Platino, M.; Plum, M.; Porowski, C.; Prado, R. R.; Privitera, P.; Prouza, M.; Quel, E. J.; Querchfeld, S.; Quinn, S.; Rautenberg, J.; Ravel, O.; Ravignani, D.; Revenu, B.; Ridky, J.; Risse, M.; Ristori, P.; Rizi, V.; Rodrigues de Carvalho, W.; Rodriguez Rojo, J.; Rodríguez-Frías, M. D.; Rogozin, D.; Rosado, J.; Roth, M.; Roulet, E.; Rovero, A. C.; Saffi, S. J.; Saftoiu, A.; Salazar, H.; Saleh, A.; Salesa Greus, F.; Salina, G.; Sanabria Gomez, J. D.; Sánchez, F.; Sanchez-Lucas, P.; Santos, E. M.; Santos, E.; Sarazin, F.; Sarkar, B.; Sarmento, R.; Sarmiento-Cano, C.; Sato, R.; Scarso, C.; Schauer, M.; Scherini, V.; Schieler, H.; Schmidt, D.; Scholten, O.; Schoorlemmer, H.; Schovánek, P.; Schröder, F. G.; Schulz, A.; Schulz, J.; Schumacher, J.; Sciutto, S. J.; Segreto, A.; Settimo, M.; Shadkam, A.; Shellard, R. C.; Sigl, G.; Sima, O.; Śmiałkowski, A.; Šmída, R.; Snow, G. R.; Sommers, P.; Sonntag, S.; Sorokin, J.; Squartini, R.; Stanca, D.; Stanič, S.; Stapleton, J.; Stasielak, J.; Strafella, F.; Stutz, A.; Suarez, F.; Suarez Durán, M.; Sudholz, T.; Suomijärvi, T.; Supanitsky, A. D.; Sutherland, M. S.; Swain, J.; Szadkowski, Z.; Taborda, O. A.; Tapia, A.; Tepe, A.; Theodoro, V. M.; Timmermans, C.; Todero Peixoto, C. J.; Tomankova, L.; Tomé, B.; Tonachini, A.; Torralba Elipe, G.; Torres Machado, D.; Travnicek, P.; Trini, M.; Ulrich, R.; Unger, M.; Urban, M.; Valbuena-Delgado, A.; Valdés Galicia, J. F.; Valiño, I.; Valore, L.; van Aar, G.; van Bodegom, P.; van den Berg, A. M.; van Vliet, A.; Varela, E.; Vargas Cárdenas, B.; Varner, G.; Vázquez, J. R.; Vázquez, R. A.; Veberič, D.; Verzi, V.; Vicha, J.; Videla, M.; Villaseñor, L.; Vorobiov, S.; Wahlberg, H.; Wainberg, O.; Walz, D.; Watson, A. A.; Weber, M.; Weindl, A.; Wiencke, L.; Wilczyński, H.; Winchen, T.; Wittkowski, D.; Wundheiler, B.; Wykes, S.; Yang, L.; Yapici, T.; Yelos, D.; Zas, E.; Zavrtanik, D.; Zavrtanik, M.; Zepeda, A.; Zimmermann, B.; Ziolkowski, M.; Zong, Z.; Zuccarello, F.; Pierre Auger Collaboration

2016-11-01

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6-16 EeV (ECM=110 - 170 TeV ), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. The average hadronic shower is 1.33 ±0.16 (1.61 ±0.21 ) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

Testing Hadronic Interactions at Ultrahigh Energies with Air Showers Measured by the Pierre Auger Observatory.

PubMed

Aab, A; Abreu, P; Aglietta, M; Ahn, E J; Al Samarai, I; Albuquerque, I F M; Allekotte, I; Allen, J D; Allison, P; Almela, A; Alvarez Castillo, J; Alvarez-Muñiz, J; Ambrosio, M; Anastasi, G A; Anchordoqui, L; Andrada, B; Andringa, S; Aramo, C; Arqueros, F; Arsene, N; Asorey, H; Assis, P; Aublin, J; Avila, G; Badescu, A M; Baus, C; Beatty, J J; Becker, K H; Bellido, J A; Berat, C; Bertaina, M E; Bertou, X; Biermann, P L; Billoir, P; Biteau, J; Blaess, S G; Blanco, A; Blazek, J; Bleve, C; Blümer, H; Boháčová, M; Boncioli, D; Bonifazi, C; Borodai, N; Botti, A M; Brack, J; Brancus, I; Bretz, T; Bridgeman, A; Briechle, F L; Buchholz, P; Bueno, A; Buitink, S; Buscemi, M; Caballero-Mora, K S; Caccianiga, B; Caccianiga, L; Cancio, A; Canfora, F; Caramete, L; Caruso, R; Castellina, A; Cataldi, G; Cazon, L; Cester, R; Chavez, A G; Chiavassa, A; Chinellato, J A; Chirinos Diaz, J C; Chudoba, J; Clay, R W; Colalillo, R; Coleman, A; Collica, L; Coluccia, M R; Conceição, R; Contreras, F; Cooper, M J; Coutu, S; Covault, C E; Cronin, J; Dallier, R; D'Amico, S; Daniel, B; Dasso, S; Daumiller, K; Dawson, B R; de Almeida, R M; de Jong, S J; De Mauro, G; de Mello Neto, J R T; De Mitri, I; de Oliveira, J; de Souza, V; Debatin, J; Del Peral, L; Deligny, O; Dhital, N; Di Giulio, C; Di Matteo, A; Díaz Castro, M L; Diogo, F; Dobrigkeit, C; D'Olivo, J C; Dorofeev, A; Dos Anjos, R C; Dova, M T; Dundovic, A; Ebr, J; Engel, R; Erdmann, M; Erfani, M; Escobar, C O; Espadanal, J; Etchegoyen, A; Falcke, H; Fang, K; Farrar, G R; Fauth, A C; Fazzini, N; Ferguson, A P; Fick, B; Figueira, J M; Filevich, A; Filipčič, A; Fratu, O; Freire, M M; Fujii, T; Fuster, A; Gallo, F; García, B; Garcia-Pinto, D; Gate, F; Gemmeke, H; Gherghel-Lascu, A; Ghia, P L; Giaccari, U; Giammarchi, M; Giller, M; Głas, D; Glaser, C; Glass, H; Golup, G; Gómez Berisso, M; Gómez Vitale, P F; González, N; Gookin, B; Gordon, J; Gorgi, A; Gorham, P; Gouffon, P; Griffith, N; Grillo, A F; Grubb, T D; Guarino, F; Guedes, G P; Hampel, M R; Hansen, P; Harari, D; Harrison, T A; Harton, J L; Hasankiadeh, Q; Haungs, A; Hebbeker, T; Heck, D; Heimann, P; Herve, A E; Hill, G C; Hojvat, C; Hollon, N; Holt, E; Homola, P; Hörandel, J R; Horvath, P; Hrabovský, M; Huege, T; Hulsman, J; Insolia, A; Isar, P G; Jandt, I; Jansen, S; Jarne, C; Johnsen, J A; Josebachuili, M; Kääpä, A; Kambeitz, O; Kampert, K H; Kasper, P; Katkov, I; Keilhauer, B; Kemp, E; Kieckhafer, R M; Klages, H O; Kleifges, M; Kleinfeller, J; Krause, R; Krohm, N; Kuempel, D; Kukec Mezek, G; Kunka, N; Kuotb Awad, A; LaHurd, D; Latronico, L; Lauscher, M; Lautridou, P; Lebrun, P; Legumina, R; Leigui de Oliveira, M A; Letessier-Selvon, A; Lhenry-Yvon, I; Link, K; Lopes, L; López, R; López Casado, A; Lucero, A; Malacari, M; Mallamaci, M; Mandat, D; Mantsch, P; Mariazzi, A G; Marin, V; Mariş, I C; Marsella, G; Martello, D; Martinez, H; Martínez Bravo, O; Masías Meza, J J; Mathes, H J; Mathys, S; Matthews, J; Matthews, J A J; Matthiae, G; Maurizio, D; Mayotte, E; Mazur, P O; Medina, C; Medina-Tanco, G; Mello, V B B; Melo, D; Menshikov, A; Messina, S; Micheletti, M I; Middendorf, L; Minaya, I A; Miramonti, L; Mitrica, B; Molina-Bueno, L; Mollerach, S; Montanet, F; Morello, C; Mostafá, M; Moura, C A; Müller, G; Muller, M A; Müller, S; Naranjo, I; Navas, S; Necesal, P; Nellen, L; Nelles, A; Neuser, J; Nguyen, P H; Niculescu-Oglinzanu, M; Niechciol, M; Niemietz, L; Niggemann, T; Nitz, D; Nosek, D; Novotny, V; Nožka, H; Núñez, L A; Ochilo, L; Oikonomou, F; Olinto, A; Pakk Selmi-Dei, D; Palatka, M; Pallotta, J; Papenbreer, P; Parente, G; Parra, A; Paul, T; Pech, M; Pedreira, F; Pękala, J; Pelayo, R; Peña-Rodriguez, J; Pepe, I M; Pereira, L A S; Perrone, L; Petermann, E; Peters, C; Petrera, S; Phuntsok, J; Piegaia, R; Pierog, T; Pieroni, P; Pimenta, M; Pirronello, V; Platino, M; Plum, M; Porowski, C; Prado, R R; Privitera, P; Prouza, M; Quel, E J; Querchfeld, S; Quinn, S; Rautenberg, J; Ravel, O; Ravignani, D; Revenu, B; Ridky, J; Risse, M; Ristori, P; Rizi, V; Rodrigues de Carvalho, W; Rodriguez Rojo, J; Rodríguez-Frías, M D; Rogozin, D; Rosado, J; Roth, M; Roulet, E; Rovero, A C; Saffi, S J; Saftoiu, A; Salazar, H; Saleh, A; Salesa Greus, F; Salina, G; Sanabria Gomez, J D; Sánchez, F; Sanchez-Lucas, P; Santos, E M; Santos, E; Sarazin, F; Sarkar, B; Sarmento, R; Sarmiento-Cano, C; Sato, R; Scarso, C; Schauer, M; Scherini, V; Schieler, H; Schmidt, D; Scholten, O; Schoorlemmer, H; Schovánek, P; Schröder, F G; Schulz, A; Schulz, J; Schumacher, J; Sciutto, S J; Segreto, A; Settimo, M; Shadkam, A; Shellard, R C; Sigl, G; Sima, O; Śmiałkowski, A; Šmída, R; Snow, G R; Sommers, P; Sonntag, S; Sorokin, J; Squartini, R; Stanca, D; Stanič, S; Stapleton, J; Stasielak, J; Strafella, F; Stutz, A; Suarez, F; Suarez Durán, M; Sudholz, T; Suomijärvi, T; Supanitsky, A D; Sutherland, M S; Swain, J; Szadkowski, Z; Taborda, O A; Tapia, A; Tepe, A; Theodoro, V M; Timmermans, C; Todero Peixoto, C J; Tomankova, L; Tomé, B; Tonachini, A; Torralba Elipe, G; Torres Machado, D; Travnicek, P; Trini, M; Ulrich, R; Unger, M; Urban, M; Valbuena-Delgado, A; Valdés Galicia, J F; Valiño, I; Valore, L; van Aar, G; van Bodegom, P; van den Berg, A M; van Vliet, A; Varela, E; Vargas Cárdenas, B; Varner, G; Vázquez, J R; Vázquez, R A; Veberič, D; Verzi, V; Vicha, J; Videla, M; Villaseñor, L; Vorobiov, S; Wahlberg, H; Wainberg, O; Walz, D; Watson, A A; Weber, M; Weindl, A; Wiencke, L; Wilczyński, H; Winchen, T; Wittkowski, D; Wundheiler, B; Wykes, S; Yang, L; Yapici, T; Yelos, D; Zas, E; Zavrtanik, D; Zavrtanik, M; Zepeda, A; Zimmermann, B; Ziolkowski, M; Zong, Z; Zuccarello, F

2016-11-04

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6-16 EeV (E_{CM}=110-170  TeV), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. The average hadronic shower is 1.33±0.16 (1.61±0.21) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

Effect of p16 Status on the Quality-of-Life Experience During Chemoradiation for Locally Advanced Oropharyngeal Cancer: A Substudy of Randomized Trial Trans-Tasman Radiation Oncology Group (TROG) 02.02 (HeadSTART).

PubMed

Ringash, Jolie; Fisher, Richard; Peters, Lester; Trotti, Andy; O'Sullivan, Brian; Corry, June; Kenny, Lizbeth; Nuyts, Sandra; Wratten, Chris; Rischin, Danny

2017-03-15

Human papillomavirus-associated oropharyngeal cancer (OPC) has a favorable prognosis. Current research de-escalates treatment, aiming to improve quality of life (QOL). Understanding the QOL experience with current standard treatment (chemoradiation therapy) provides context for emerging data. We report the impact of p16 status on QOL for patients with stage III or IV OPC undergoing chemoradiation therapy in an international phase 3 trial (TROG 02.02 [HeadSTART]). A subgroup analysis by p16 status was conducted in patients with OPC treated in a phase 3 randomized trial. The study subset with OPC and known p16 status was mainly from Australasia, Western Europe, and North America. Of 861 participants, 200 had OPC, known p16 status, and baseline QOL data; 82 were p16 negative and 118 were p16 positive. Radiation therapy (70 Gy over a period of 7 weeks) was given concurrently with 3 cycles of either cisplatin (100 mg/m 2 ) or cisplatin (75 mg/m 2 ) plus tirapazamine. QOL was measured with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) questionnaire at baseline and 2, 6, 12, 23, and 38 months. Because no significant difference in QOL score was observed between arms, results by p16 status are reported with arms combined. The p16-positive patients were younger, had a better Eastern Cooperative Oncology Group performance status, and were less often current smokers. Our primary hypothesis that the change in FACT-H&N score from baseline to 6 months would be more favorable in the p16-positive cohort was not met (p16 positive, -6.3; p16 negative, -1.8; P=.14). The mean baseline FACT-H&N score was statistically and clinically significantly better in p16-positive patients (111 vs 102, P<.001); at 2 months, scores declined in both groups but more dramatically for p16-positive patients. By 12 months, p16-positive patients again had superior scores. A higher baseline FACT-H&N score and p16-positive status were independent predictors of overall survival. Patients with p16-positive OPC exhibited better baseline QOL but showed a more dramatic QOL drop with concurrent chemoradiation. Given the favorable prognosis of p16-positive OPC, efforts to reduce the QOL burden of treatment are warranted. Copyright © 2016 Elsevier Inc. All rights reserved.

Interaction between Water and Wind as a Driver of Passive Dispersal in Mangroves

PubMed Central

Van der Stocken, Tom; Vanschoenwinkel, Bram; De Ryck, Dennis J. R.; Bouma, Tjeerd J.; Dahdouh-Guebas, Farid; Koedam, Nico

2015-01-01

Although knowledge on dispersal patterns is essential for predicting long-term population dynamics, critical information on the modalities of passive dispersal and potential interactions between vectors is often missing. Here, we use mangrove propagules with a wide variety of morphologies to investigate the interaction between water and wind as a driver of passive dispersal. We imposed 16 combinations of wind and hydrodynamic conditions in a flume tank, using propagules of six important mangrove species (and genera), resulting in a set of dispersal morphologies that covers most variation present in mangrove propagules worldwide. Additionally, we discussed the broader implications of the outcome of this flume study on the potential of long distance dispersal for mangrove propagules in nature, applying a conceptual model to a natural mangrove system in Gazi Bay (Kenya). Overall, the effect of wind on dispersal depended on propagule density (g l-1). The low-density Heritiera littoralis propagules were most affected by wind, while the high-density vertically floating propagules of Ceriops tagal and Bruguiera gymnorrhiza were least affected. Avicennia marina, and horizontally floating Rhizophora mucronata and C. tagal propagules behaved similarly. Morphological propagule traits, such as the dorsal sail of H. littoralis, explained another part of the interspecific differences. Within species, differences in dispersal velocities can be explained by differences in density and for H. littoralis also by variations in the shape of the dorsal sail. Our conceptual model illustrates that different propagule types have a different likelihood of reaching the open ocean depending on prevailing water and wind currents. Results suggest that in open water, propagule traits (density, morphology, and floating orientation) appear to determine the effect of water and wind currents on dispersal dynamics. This has important implications for inter- and intraspecific variation in dispersal patterns and the likelihood of reaching suitable habitat patches within a propagule's viable period. PMID:25811191

Cognitive development in children of adolescent mothers: The impact of socioeconomic risk and maternal sensitivity.

PubMed

Firk, Christine; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Scharke, Wolfgang; Dahmen, Brigitte

2018-02-01

Adolescent motherhood is accompanied by a constellation of risk factors that translate into developmental risk for the off-spring. Socioeconomic risk that is associated with adolescent motherhood as well as maternal interactive behaviors may contribute to the impact of adolescent motherhood on children's developmental outcome. Therefore, the aim of the current study was to investigate differences in children's cognitive development between children of adolescent and adult mothers in their first two years of life and to examine whether socioeconomic risk (e.g. such as educational and financial problems) and/or maternal sensitivity mediate developmental differences between children of adolescent and adult mothers. Adolescent mothers (<21 years; N = 64) and adult mothers (>25 years; N = 34) and their infants were included in the current study. Child cognitive development and maternal sensitivity were assessed at three different time points (T1: mean child age 5.26 months; T2: mean child age 14.69 months; T3: mean child age 21.16 months). Children of adult mothers showed better cognitive performance at T3 compared to children of adolescent mothers but not at T1 and T2. A multiple mediation model including socioeconomic risk and maternal sensitivity as serial mediators demonstrated that the effect of adolescent motherhood on cognitive development was mediated in a causal effect chain with socioeconomic risk negatively affecting maternal sensitivity and maternal sensitivity affecting children's cognitive development. The present findings demonstrate that maternal interactive behaviors are not only a simple predictor of cognitive development but may also act as a mediator of the association between more distal variables such as socioeconomic risk and cognitive development in adolescent mothers. This supports the need to promote prevention and intervention programs for adolescent mothers during the early postpartum period to reduce socioeconomic problems and enhance maternal interactive behaviors. Copyright © 2018 Elsevier Inc. All rights reserved.

Development of Novel p16INK4a Mimetics as Anticancer Therapy

DTIC Science & Technology

2015-10-01

peptide (or substituted peptide) or the crystal structure of the relevant sequence from p16INK4 ( PDB 1BI7) was used as the starting structure . Model...small peptides that interact with CDK4/6. The specific aims are as follows. (1) Determine structure -function relationships of overlapping peptides...Determine structure -function relationships of overlapping peptides derived from p16 INK4a that inhibit the activity of CDK4/6 and identify stabilized

Current and Past Maternal Depression, Maternal Interaction Behaviors, and Children's Externalizing and Internalizing Symptoms

ERIC Educational Resources Information Center

Foster, Cynthia J. Ewell; Garber, Judy; Durlak, Joseph A.

2008-01-01

Relations among past maternal depressive disorder, current depressive symptoms, current maternal interaction behaviors, and children's adjustment were examined in a sample of 204 women and their young adolescent offspring (mean age = 11.86, SD = 0.55). Mothers either had (n = 157) or had not (n = 57) experienced at least one depressive disorder…

First Global Observations of the Interstellar Interaction from the Interstellar Boundary Explorer (Invited)

NASA Astrophysics Data System (ADS)

McComas, D. J.

2009-12-01

The Sun moves through the local interstellar medium, continuously emitting ionized, supersonic solar wind plasma and carving out a cavity in interstellar space, called the heliosphere. The Interstellar Boundary Explorer (IBEX) spacecraft has just completed the first all-sky maps of the interstellar interaction at the edge of the heliosphere, by imaging energetic neutral atoms (ENAs) emanating from this region. IBEX all-sky maps and energy spectra provide detailed information about the interaction. Our observations show globally distributed fluxes ordered by the solar wind structure, which are superposed by another, unexpected feature, which is neither seen by the Voyager spacecraft nor predicted by any current model or theory. This talk summarizes the IBEX observations, shares our unexpected results, and discusses some of the possible ideas for what may be missing in our current understanding of the heliosphere’s global interaction. IBEX Science Team: D.J. McComas1,2, F. Allegrini1,2, P. Bochsler3, M. Bzowski4, E.R. Christian5, G.B. Crew6, R. DeMajistre7, H. Fahr8, H. Fichtner9, P.C. Frisch10, H.O. Funsten11, S. A. Fuselier12, G. Gloeckler13, M. Gruntman14, J. Heerikhuisen15, V. Izmodenov16, P. Janzen17, P. Knappenberger18, S. Krimigis7,19, H. Kucharek20, M. Lee20, G. Livadiotis1, S. Livi1,2, R.J. MacDowall5, D. Mitchell7, E. Möbius20, T. Moore5, N.V. Pogorelov15, D. Reisenfeld17, E. Roelof7, L. Saul3, N.A. Schwadron21, P.W. Valek1,2, R. Vanderspek6, P. Wurz3, G.P. Zank15 (1)Southwest Research Institute, San Antonio, TX, USA (2) University of Texas at San Antonio, San Antonio, TX, USA (3)University of Bern, Physikalisches Institut, CH-3012 Bern, Switzerland (4)Space Research Centre of the Polish Academy of Sciences, Warsaw, Poland (5)NASA Goddard Space Flight Center, Greenbelt, MD, USA (6)Massachusetts Institute of Technology, Cambridge, MA, USA (7)Applied Physics Laboratory, Johns Hopkins University, Laurel, MD, USA (8)University of Bonn, Bonn, Germany (9)Ruhr-Universitaet Bochum, Bochum, Germany (10)University of Chicago, Chicago, IL, USA (11)Los Alamos National Laboratory, Los Alamos, NM, USA (12)Lockheed Martin Advanced Technology Center, Palo Alto, CA, USA (13)University of Michigan, Ann Arbor, MI, USA (14)University of Southern California, Los Angeles, CA, USA (15)University of Alabama, Huntsville, AL, USA (16) Moscow State University; Space Research Institute (IKI) and Institute for Problems in Mechanics Russian Academy of Sciences, Moscow, Russia (17)University of Montana, Missoula, MT, USA (18)Adler Planetarium, Chicago, IL, USA (19)Office for Space Research and Technology, Academy of Athens, Athens, Greece (20)University of New Hampshire, Space Science Center, Durham, NH, USA (21) Boston University, Boston, MA, USA

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions

DOE PAGES

Aguilar-Arevalo, A. A.; Brown, B. C.; Bugel, L.; ...

2018-04-06

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (more » $$K^+ \\rightarrow \\mu^+ \

First Measurement of Monoenergetic Muon Neutrino Charged Current Interactions

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

Aguilar-Arevalo, A. A.; Brown, B. C.; Bugel, L.

We report the first measurement of monoenergetic muon neutrino charged current interactions. MiniBooNE has isolated 236 MeV muon neutrino events originating from charged kaon decay at rest (more » $$K^+ \\rightarrow \\mu^+ \

Task Validation for Studies on Fragmented Sleep and Cognitive Efficiency under Stress

DTIC Science & Technology

1982-11-01

43 10 Interactions Between Sex and Xenoid Dispersion ........ ... 48 11 Percent Weapon Commands Issued Without Adequate Shield...42 15 Variables Showing Significant Main Effects for Sex of Subject...45 H16 Significant Interactions Between Sex and Xenoid Dispersion .. ............................................46 17 Experimental Design of the

Transient Dynamic Response and Failure of Composite Structure Under Cyclic Loading with Fluid Structure Interaction

DTIC Science & Technology

2014-09-01

TERMS fluid structure interaction, composite structures shipbuilding, fatigue loading 15. NUMBER OF PAGES 85 16. PRICE CODE 17. SECURITY...under the three point bending test. All the composites exhibit an initial nonlinear and inelastic deformation trend and end with a catastrophic abrupt

Spectral and temporal characteristics of target current and electromagnetic pulse induced by nanosecond laser ablation

NASA Astrophysics Data System (ADS)

Krása, J.; De Marco, M.; Cikhardt, J.; Pfeifer, M.; Velyhan, A.; Klír, D.; Řezáč, K.; Limpouch, J.; Krouský, E.; Dostál, J.; Ullschmied, J.; Dudžák, R.

2017-06-01

The current balancing the target charging and the emission of transient electromagnetic pulses (EMP) driven by the interaction of a focused 1.315 μm iodine 300 ps PALS laser with metallic and plastic targets were measured with the use of inductive probes. It is experimentally proven that the duration of return target currents and EMPs is much longer than the duration of laser-target interaction. The laser-produced plasma is active after the laser-target interaction. During this phase, the target acts as a virtual cathode and the plasma-target interface expands. A double exponential function is used in order to obtain the temporal characteristics of EMP. The rise time of EMPs fluctuates in the range up to a few tens of nanoseconds. Frequency spectra of EMP and target currents are modified by resonant frequencies of the interaction chamber.

The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line

PubMed Central

Carvalho, Fernanda Caroline; Soares, Sandro Gomes; Tamarozzi, Mirela Barros; Rego, Eduardo Magalhães; Roque-Barreira, Maria-Cristina

2011-01-01

ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment. PMID:22132163

Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-16-1-0785 TITLE: Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function...2016 - 29 Sep 2017 4. TITLE AND SUBTITLE Prosthetic Smart Socket Technology to Improve Patient Interaction, Usability, Comfort, Fit and Function 5a...discomfort. 2. KEYWORDS: Provide a brief list of keywords (limit to 20 words). Prosthesis, prosthesis fit, technology , skin problems, amputee

Quantum rings in magnetic fields and spin current generation.

PubMed

Cini, Michele; Bellucci, Stefano

2014-04-09

We propose three different mechanisms for pumping spin-polarized currents in a ballistic circuit using a time-dependent magnetic field acting on an asymmetrically connected quantum ring at half filling. The first mechanism works thanks to a rotating magnetic field and produces an alternating current with a partial spin polarization. The second mechanism works by rotating the ring in a constant field; like the former case, it produces an alternating charge current, but the spin current is dc. Both methods do not require a spin-orbit interaction to achieve the polarized current, but the rotating ring could be used to measure the spin-orbit interaction in the ring using characteristic oscillations. On the other hand, the last mechanism that we propose depends on the spin-orbit interaction in an essential way, and requires a time-dependent magnetic field in the plane of the ring. This arrangement can be designed to pump a purely spin current. The absence of a charge current is demonstrated analytically. Moreover, a simple formula for the current is derived and compared with the numerical results.

Summarizing techniques that combine three non-parametric scores to detect disease-associated 2-way SNP-SNP interactions.

PubMed

Sengupta Chattopadhyay, Amrita; Hsiao, Ching-Lin; Chang, Chien Ching; Lian, Ie-Bin; Fann, Cathy S J

2014-01-01

Identifying susceptibility genes that influence complex diseases is extremely difficult because loci often influence the disease state through genetic interactions. Numerous approaches to detect disease-associated SNP-SNP interactions have been developed, but none consistently generates high-quality results under different disease scenarios. Using summarizing techniques to combine a number of existing methods may provide a solution to this problem. Here we used three popular non-parametric methods-Gini, absolute probability difference (APD), and entropy-to develop two novel summary scores, namely principle component score (PCS) and Z-sum score (ZSS), with which to predict disease-associated genetic interactions. We used a simulation study to compare performance of the non-parametric scores, the summary scores, the scaled-sum score (SSS; used in polymorphism interaction analysis (PIA)), and the multifactor dimensionality reduction (MDR). The non-parametric methods achieved high power, but no non-parametric method outperformed all others under a variety of epistatic scenarios. PCS and ZSS, however, outperformed MDR. PCS, ZSS and SSS displayed controlled type-I-errors (<0.05) compared to GS, APDS, ES (>0.05). A real data study using the genetic-analysis-workshop 16 (GAW 16) rheumatoid arthritis dataset identified a number of interesting SNP-SNP interactions. © 2013 Elsevier B.V. All rights reserved.

Effect of HPV16 L1 virus-like particles on the aggregation of non-functionalized gold nanoparticles.

PubMed

Palomino-Vizcaino, Giovanni; Valencia Reséndiz, Diana Gabriela; Benítez-Hess, María Luisa; Martínez-Acuña, Natalia; Tapia-Vieyra, Juana Virginia; Bahena, Daniel; Díaz-Sánchez, Mauricio; García-González, Octavio Patricio; Alvarez-Sandoval, Brenda Arizaí; Alvarez-Salas, Luis Marat

2018-02-15

Colorimetric assays based on gold nanoparticles (GNPs) are of considerable interest for diagnostics because of their simplicity and low-cost. Nevertheless, a deep understanding of the interaction between the GNPs and the intended molecular target is critical for the development of reliable detection technologies. The present report describes the spontaneous interaction between HPV16 L1 virus-like particles (VLPs) and non-functionalized GNPs (nfGNPs) resulting in the inhibition of nfGNPs salt-induced aggregation and the stabilization of purified VLPs. Ionic-competition experiments suggested that the nature of nfGNPs-VLPs interaction is non-covalent. Adsorption of an RNA aptamer on nfGNPs surface showed an additive aggregation-inhibitory effect. The use of mutant VLPs confirmed that the interaction nfGNPs-VLPs is not mediated by the opposing superficial electrostatic charges, suggesting that non-electrostatic forces participate in the arrangement of nfGNPs on the VLPs surface. Competition experiments using increasing ethanol concentrations on nfGNPs-VLPs complexes suggested hydrophobic interactions as the main stabilizing force. Therefore, the nfGNPs-VLPs interaction described here should facilitate the development of adsorption assays based on nfGNPs for HPV detection and cervical cancer prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

PubMed

Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

2017-12-12

Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

PubMed Central

Sutherland, Jeffrey J.; Daly, Thomas M.; Liu, Xiong; Goldstein, Keith; Johnston, Joseph A.; Ryan, Timothy P.

2015-01-01

Pharmaceutical prescribing and drug-drug interaction data underlie recommendations on drug combinations that should be avoided or closely monitored by prescribers. Because the number of patients taking multiple medications is increasing, a comprehensive view of prescribing patterns in patients is important to better assess real world pharmaceutical response and evaluate the potential for multi-drug interactions. We obtained self-reported prescription data from NHANES surveys between 1999 and 2010, and confirm the previously reported finding of increasing drug use in the elderly. We studied co-prescription drug trends by focusing on the 2009-2010 survey, which contains prescription data on 690 drugs used by 10,537 subjects. We found that medication profiles were unique for individuals aged 65 years or more, with ≥98 unique drug regimens encountered per 100 subjects taking 3 or more medications. When drugs were viewed by therapeutic class, it was found that the most commonly prescribed drugs were not the most commonly co-prescribed drugs for any of the 16 drug classes investigated. We cross-referenced these medication lists with drug interaction data from Drugs.com to evaluate the potential for drug interactions. The number of drug alerts rose proportionally with the number of co-prescribed medications, rising from 3.3 alerts for individuals prescribed 5 medications to 11.7 alerts for individuals prescribed 10 medications. We found 22% of elderly subjects taking both a substrate and inhibitor of a given cytochrome P450 enzyme, and 4% taking multiple inhibitors of the same enzyme simultaneously. By examining drug pairs prescribed in 0.1% of the population or more, we found low agreement between co-prescription rate and co-discussion in the literature. These data show that prescribing trends in treatment could drive a large extent of individual variability in drug response, and that current pairwise approaches to assessing drug-drug interactions may be inadequate for predicting real world outcomes. PMID:25739022

Inhibition of OCT2, MATE1 and MATE2-K as a possible mechanism of drug interaction between pazopanib and cisplatin.

PubMed

Sauzay, C; White-Koning, M; Hennebelle, I; Deluche, T; Delmas, C; Imbs, D C; Chatelut, E; Thomas, F

2016-08-01

We hypothesized that pazopanib is an inhibitor of cisplatin renal transporters OCT2, MATE1 and MATE2-K based on previous studies demonstrating an interaction between tyrosine kinase inhibitors and these transporters. Because several combinations of targeted therapies and cytotoxics are currently in development for cancer treatment, such an interaction is worth investigating. Experiments on HEK293 cells stably transfected to express OCT2, MATE1, MATE2-K or an empty vector (EV) were conducted. The inhibitory effect of pazopanib on these transporters was measured using the uptake of fluorescent substrate ASP+ and cisplatin in the different cell lines. The effect of pazopanib on cisplatin-induced cytotoxicity was also evaluated. A decrease of ASP+ uptake was observed in OCT2-HEK, MATE1-HEK and MATE2K-HEK cell lines after addition of pazopanib at increasing concentrations. Pazopanib inhibited cisplatin specific uptake in OCT2-HEK, MATE1-HEK and MATE2K-HEK lines. Cytotoxicity experiments showed that co-incubation of cisplatin with pazopanib multiplied up to 2.7, 2.4 and 1.6 times the EC50 values of cisplatin in OCT2-HEK, MATE1-HEK and MATE2K-HEK cell lines respectively, reaching about the same values as in EV-HEK cells. To conclude, pazopanib inhibits OCT2, MATE1 and MATE2-K, which are involved in cisplatin secretion into urine. The combination of these two drugs may lead to an interaction and increase the cisplatin-induced systemic toxicity. Given the wide variability of plasma pazopanib concentrations observed in vivo, the interaction may occur in a clinical setting, particularly in overexposed patients. The existence of a drug-drug interaction should be investigated when pazopanib is associated with a substrate of these transporters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Propafenone effects on the stable structures of Aβ16-22 system

NASA Astrophysics Data System (ADS)

Tran, Linh; Ngo, Son Tung; Nguyen, Minh Tho

2018-03-01

An extensive replica exchange molecular dynamics (REMD) simulation was performed to investigate the progress patterns of the molecular interactions of propafenone and Aβ16-22 system. Distinct conformational equilibrium of Aβ16-22 system with and without propafenone was analyzed in detail. Propafenone can act to prevent the Alzheimer's disease (AD) by significantly inhibiting Aβ oligomerization. Our calculated results provide insights into the inhibition mechanism of propafenone on the oligomerization process to form Aβ16-22 peptide aggregation. These findings are valuable for the development of therapeutic drugs in the AD early stage.

Study of the Hyperon-Nucleon Interaction in Exclusive Λ Photoproduction off the Deuteron

NASA Astrophysics Data System (ADS)

Zachariou, Nicholas; CLAS Collaboration

2014-09-01

Understanding the nature of the nuclear force in terms of the fundamental degrees of freedom of the theory of strong interaction, Quantum Chromodynamics (QCD), is one of the primary goals of modern nuclear physics. While the nucleon-nucleon (NN) interaction has been studied for decades, a systematic description of the NN potential has been achieved only recently with the development of low-energy Effective Field Theories (EFT). To obtain a comprehensive understanding of the strong interaction, dynamics involving strange baryons must be studied. Currently, little is known about the properties of the hyperon-nucleon (YN) and the hyperon-hyperon (YY) interactions. In this talk I will describe our current research of the Λn interaction using the E06-103 experiment performed with the CLAS detector in Hall B at Jefferson Lab. The large kinematic coverage of the CLAS combined with the exceptionally high quality of the experimental data allows to identify and select final-state interaction events in the reaction γd -->K+ Λn and to establish their kinematical dependencies. The large set of observables we aim to obtain will provide tight constraints on modern YN potentials. I will present the current status of the project and will discuss future incentives. Understanding the nature of the nuclear force in terms of the fundamental degrees of freedom of the theory of strong interaction, Quantum Chromodynamics (QCD), is one of the primary goals of modern nuclear physics. While the nucleon-nucleon (NN) interaction has been studied for decades, a systematic description of the NN potential has been achieved only recently with the development of low-energy Effective Field Theories (EFT). To obtain a comprehensive understanding of the strong interaction, dynamics involving strange baryons must be studied. Currently, little is known about the properties of the hyperon-nucleon (YN) and the hyperon-hyperon (YY) interactions. In this talk I will describe our current research of the Λn interaction using the E06-103 experiment performed with the CLAS detector in Hall B at Jefferson Lab. The large kinematic coverage of the CLAS combined with the exceptionally high quality of the experimental data allows to identify and select final-state interaction events in the reaction γd -->K+ Λn and to establish their kinematical dependencies. The large set of observables we aim to obtain will provide tight constraints on modern YN potentials. I will present the current status of the project and will discuss future incentives. for the CLAS Collaboration.

The beneficial metabolic effects of insulin sensitizers are not attenuated by mitochondrial pyruvate carrier 2 hypomorphism.

PubMed

Vigueira, Patrick A; McCommis, Kyle S; Hodges, Wesley T; Schweitzer, George G; Cole, Serena L; Oonthonpan, Lalita; Taylor, Eric B; McDonald, William G; Kletzien, Rolf F; Colca, Jerry R; Finck, Brian N

2017-08-01

What is the central question of this study? The antidiabetic effects of thiazolidinedione (TZD) drugs may be mediated in part by a molecular interaction with the constituent proteins of the mitochondrial pyruvate carrier complex (MPC1 and MPC2). We examined the ability of a mutant mouse strain expressing an N-terminal truncation of MPC2 (Mpc2Δ16 mice) to respond to TZD treatment. What is the main finding and its importance? The response of Mpc2Δ16 mice to TZD treatment was not significantly different from that of wild-type C57BL6/J control animals, suggesting that the 16 N-terminal amino acids of MPC2 are dispensable for the effects of TZD treatment. Rosiglitazone and pioglitazone are thiazolidinedione (TZD) compounds that have been used clinically as insulin-sensitizing drugs and are generally believed to mediate their effects via activation of the peroxisome proliferator-activated receptor γ (PPARγ). Recent work has shown that it is possible to synthesize TZD compounds with potent insulin-sensitizing effects and markedly diminished affinity for PPARγ. Both clinically used TZDs and investigational PPARγ-sparing TZDs, such as MSDC-0602, interact with the mitochondrial pyruvate carrier (MPC) and inhibit its activity. The MPC complex is composed of two proteins, MPC1 and MPC2. Herein, we used mice expressing a hypomorphic MPC2 protein missing 16 amino acids in the N-terminus (Mpc2Δ16 mice) to determine the effects of these residues in mediating the insulin-sensitizing effects of TZDs in diet-induced obese mice. We found that both pioglitazone and MSDC-0602 elicited their beneficial metabolic effects, including improvement in glucose tolerance, attenuation of hepatic steatosis, reduction of adipose tissue inflammation and stimulation of adipocyte browning, in both wild-type and Mpc2Δ16 mice after high-fat diet feeding. In addition, truncation of MPC2 failed to attenuate the interaction between TZDs and the MPC in a bioluminescence resonance energy transfer-based assay or to affect the suppression of pyruvate-stimulated respiration in cells. Collectively, these data suggest that the interaction between TZDs and MPC2 is not affected by loss of the N-terminal 16 amino acids nor are these residues required for the insulin-sensitizing effects of these compounds. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Histone modifications influence mediator interactions with chromatin

PubMed Central

Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

2011-01-01

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

Unsteady separation in sharp fin-induced shock wave/turbulent boundary layer interaction at Mach 5

NASA Technical Reports Server (NTRS)

Schmisseur, J. D.; Dolling, D. S.

1992-01-01

Fluctuating wall-pressure measurements are made in shock-wave/turbulent-boundary-layer interactions generated by sharp/unswept fins at angles of attack of 16, 18, 20, 22, 24, 26, and 28 degrees at Mach 5. The experiment was conducted under approximately adiabatic wall temperature conditions. The mean and rms pressure distributions can be collapsed in conical coordinates. The wall-pressure signal near separation is intermittent for all angles of attack (16-28 deg) and is qualitatively similar to that measured in unswept flows. However, the shock frequencies are higher - about 5 kHz compared to 0.5-1 kHz. Over the range of sweepbacks examined, from 25-55 deg, the spectral content of the fluctuating pressures does not change. Thus, the increase in separation-shock frequency from 1 to 5 kHz occurs at lower interaction sweepback and is not a continuous process with increasing sweepback. Power spectra at the position of maximum rms in the intermittent region for interactions in different incoming boundary layers have the same center frequency. The maximum rms in the intermittent region correlates with interaction sweepback, not with overall inviscid pressure rise.

Fluorographene based Ultrasensitive Ammonia Sensor

PubMed Central

Tadi, Kiran Kumar; Pal, Shubhadeep; Narayanan, Tharangattu N.

2016-01-01

Single molecule detection using graphene can be brought by tuning the interactions via specific dopants. Electrostatic interaction between the most electronegative element fluorine (F) and hydrogen (H) is one of the strong interactions in hydrogen bonding, and here we report the selective binding of ammonia/ammonium with F in fluorographene (FG) resulting to a change in the impedance of the system. Very low limit of detection value of ~0.44 pM with linearity over wide range of concentrations (1 pM–0.1 μM) is achieved using the FG based impedance sensor, andthisscreen printed FG sensor works in both ionized (ammonium) and un-ionized ammonia sensing platforms. The interaction energies of FG and NH3/NH4+ are evaluated using density functional theory calculations and the interactions are mapped. Here FGs with two different amounts of fluorinecontents −~5 atomic% (C39H16F2) and ~24 atomic% (C39H16F12) - are theoretically and experimentally studied for selective, high sensitive and ultra-low level detection of ammonia. Fast responding, high sensitive, large area patternable FG based sensor platform demonstrated here can open new avenues for the development of point-of-care devices and clinical sensors. PMID:27142522

A ReaxFF-based molecular dynamics study of the mechanisms of interactions between reactive oxygen plasma species and the Candida albicans cell wall

NASA Astrophysics Data System (ADS)

Zhao, T.; Shi, L.; Zhang, Y. T.; Zou, L.; Zhang, L.

2017-10-01

Atmospheric pressure non-equilibrium plasmas have attracted significant attention and have been widely used to inactivate pathogens, yet the mechanisms underlying the interactions between plasma-generated species and bio-organisms have not been elucidated clearly. In this paper, reactive molecular dynamics simulations are employed to investigate the mechanisms of interactions between reactive oxygen plasma species (O, OH, and O2) and β-1,6-glucan (a model for the C. albicans cell wall) from a microscopic point of view. Our simulations show that O and OH species can break structurally important C-C and C-O bonds, while O2 molecules exhibit only weak, non-bonded interactions with β-1,6-glucan. Hydrogen abstraction from hydroxyl or CH groups occurs first in all bond cleavage mechanisms. This is followed by a cascade of bond cleavage and double bond formation events. These lead to the destruction of the fungal cell wall. O and OH have similar effects related to their bond cleavage mechanisms. Our simulation results provide fundamental insights into the mechanisms underlying the interactions between reactive oxygen plasma species and the fungal cell wall of C. albicans at the atomic level.

Wavelet analysis of particle density functions in nucleus-nucleus interactions

NASA Astrophysics Data System (ADS)

Manna, S. K.; Haldar, P. K.; Mali, P.; Mukhopadhyay, A.; Singh, G.

A continuous wavelet analysis is performed for pattern recognition of the pseudorapidity density profile of singly charged particles produced in 16O+Ag/Br and 32S+Ag/Br interactions, each at an incident energy of 200 GeV per nucleon in the laboratory system. The experiments are compared with a model prediction based on the ultra-relativistic quantum molecular dynamics (UrQMD). To eliminate the contribution coming from known source(s) of particle cluster formation like Bose-Einstein correlation (BEC), the UrQMD output is modified by “an algorithm that mimics the BEC as an after burner.” We observe that for both interactions particle clusters are found at same pseudorapidity locations at all scales. However, the cluster locations in the 16O+Ag/Br interaction are different from those found in the 32S+Ag/Br interaction. Significant differences between experiments and simulations are revealed in the wavelet pseudorapidity spectra that can be interpreted as the preferred pseudorapidity values and/or scales of the pseudorapidity interval at which clusters of particles are formed. The observed discrepancy between experiment and corresponding simulation should therefore be interpreted in terms of some kind of nontrivial dynamics of multiparticle production.

A Dual Role for the Nonreceptor Tyrosine Kinase Pyk2 during the Intracellular Trafficking of Human Papillomavirus 16.

PubMed

Gottschalk, Elinor Y; Meneses, Patricio I

2015-09-01

The infectious process of human papillomaviruses (HPVs) has been studied considerably, and many cellular components required for viral entry and trafficking continue to be revealed. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during HPV16 pseudovirion infection of human keratinocytes. We found that Pyk2 is necessary for infection and appears to be involved in the intracellular trafficking of the virus. Small interfering RNA-mediated reduction of Pyk2 resulted in a significant decrease in infection but did not prevent viral entry at the plasma membrane. Pyk2 depletion resulted in altered endolysosomal trafficking of HPV16 and accelerated unfolding of the viral capsid. Furthermore, we observed retention of the HPV16 pseudogenome in the trans-Golgi network (TGN) in Pyk2-depleted cells, suggesting that the kinase could be required for the viral DNA to exit the TGN. While Pyk2 has previously been shown to function during the entry of enveloped viruses at the plasma membrane, the kinase has not yet been implicated in the intracellular trafficking of a nonenveloped virus such as HPV. Additionally, these data enrich the current literature on Pyk2's function in human keratinocytes. In this study, we investigated the role of the nonreceptor tyrosine kinase Pyk2 during human papillomavirus (HPV) infection of human skin cells. Infections with high-risk types of HPV such as HPV16 are the leading cause of cervical cancer and a major cause of genital and oropharyngeal cancer. As a nonenveloped virus, HPV enters cells by interacting with cellular receptors and established cellular trafficking routes to ensure that the viral DNA reaches the nucleus for productive infection. This study identified Pyk2 as a cellular component required for the intracellular trafficking of HPV16 during infection. Understanding the infectious pathways of HPVs is critical for developing additional preventive therapies. Furthermore, this study advances our knowledge of intracellular trafficking processes in keratinocytes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Controlled enhancement of spin-current emission by three-magnon splitting.

PubMed

Kurebayashi, Hidekazu; Dzyapko, Oleksandr; Demidov, Vladislav E; Fang, Dong; Ferguson, A J; Demokritov, Sergej O

2011-07-03

Spin currents--the flow of angular momentum without the simultaneous transfer of electrical charge--play an enabling role in the field of spintronics. Unlike the charge current, the spin current is not a conservative quantity within the conduction carrier system. This is due to the presence of the spin-orbit interaction that couples the spin of the carriers to angular momentum in the lattice. This spin-lattice coupling acts also as the source of damping in magnetic materials, where the precessing magnetic moment experiences a torque towards its equilibrium orientation; the excess angular momentum in the magnetic subsystem flows into the lattice. Here we show that this flow can be reversed by the three-magnon splitting process and experimentally achieve the enhancement of the spin current emitted by the interacting spin waves. This mechanism triggers angular momentum transfer from the lattice to the magnetic subsystem and modifies the spin-current emission. The finding illustrates the importance of magnon-magnon interactions for developing spin-current based electronics.

Sub-200 ps CRT in monolithic scintillator PET detectors using digital SiPM arrays and maximum likelihood interaction time estimation.

PubMed

van Dam, Herman T; Borghi, Giacomo; Seifert, Stefan; Schaart, Dennis R

2013-05-21

Digital silicon photomultiplier (dSiPM) arrays have favorable characteristics for application in monolithic scintillator detectors for time-of-flight positron emission tomography (PET). To fully exploit these benefits, a maximum likelihood interaction time estimation (MLITE) method was developed to derive the time of interaction from the multiple time stamps obtained per scintillation event. MLITE was compared to several deterministic methods. Timing measurements were performed with monolithic scintillator detectors based on novel dSiPM arrays and LSO:Ce,0.2%Ca crystals of 16 × 16 × 10 mm(3), 16 × 16 × 20 mm(3), 24 × 24 × 10 mm(3), and 24 × 24 × 20 mm(3). The best coincidence resolving times (CRTs) for pairs of identical detectors were obtained with MLITE and measured 157 ps, 185 ps, 161 ps, and 184 ps full-width-at-half-maximum (FWHM), respectively. For comparison, a small reference detector, consisting of a 3 × 3 × 5 mm(3) LSO:Ce,0.2%Ca crystal coupled to a single pixel of a dSiPM array, was measured to have a CRT as low as 120 ps FWHM. The results of this work indicate that the influence of the optical transport of the scintillation photons on the timing performance of monolithic scintillator detectors can at least partially be corrected for by utilizing the information contained in the spatio-temporal distribution of the collection of time stamps registered per scintillation event.

Sub-200 ps CRT in monolithic scintillator PET detectors using digital SiPM arrays and maximum likelihood interaction time estimation

NASA Astrophysics Data System (ADS)

van Dam, Herman T.; Borghi, Giacomo; Seifert, Stefan; Schaart, Dennis R.

2013-05-01

Digital silicon photomultiplier (dSiPM) arrays have favorable characteristics for application in monolithic scintillator detectors for time-of-flight positron emission tomography (PET). To fully exploit these benefits, a maximum likelihood interaction time estimation (MLITE) method was developed to derive the time of interaction from the multiple time stamps obtained per scintillation event. MLITE was compared to several deterministic methods. Timing measurements were performed with monolithic scintillator detectors based on novel dSiPM arrays and LSO:Ce,0.2%Ca crystals of 16 × 16 × 10 mm3, 16 × 16 × 20 mm3, 24 × 24 × 10 mm3, and 24 × 24 × 20 mm3. The best coincidence resolving times (CRTs) for pairs of identical detectors were obtained with MLITE and measured 157 ps, 185 ps, 161 ps, and 184 ps full-width-at-half-maximum (FWHM), respectively. For comparison, a small reference detector, consisting of a 3 × 3 × 5 mm3 LSO:Ce,0.2%Ca crystal coupled to a single pixel of a dSiPM array, was measured to have a CRT as low as 120 ps FWHM. The results of this work indicate that the influence of the optical transport of the scintillation photons on the timing performance of monolithic scintillator detectors can at least partially be corrected for by utilizing the information contained in the spatio-temporal distribution of the collection of time stamps registered per scintillation event.

Current Trends and Potential Applications of Microbial Interactions for Human Welfare

PubMed Central

Tshikantwa, Tiroyaone Shimane; Ullah, Muhammad Wajid; He, Feng; Yang, Guang

2018-01-01

For a long time, it was considered that interactions between microbes are only inhibitory in nature. However, latest developments in research have demonstrated that within our environment, several classes of microbes exist which produce different products upon interaction and thus embrace a wider scope of useful and potentially valuable aspects beyond simple antibiosis. Therefore, the current review explores different types of microbial interactions and describes the role of various physical, chemical, biological, and genetic factors regulating such interactions. It further explains the mechanism of action of biofilm formation and role of secondary metabolites regulating bacteria-fungi interaction. Special emphasis and focus is placed on microbial interactions which are important in medicine, food industry, agriculture, and environment. In short, this review reveals the recent contributions of microbial interaction for the benefit of mankind.

Wave-induced current considering wave-tide interaction in Haeundae

NASA Astrophysics Data System (ADS)

Lim, Hak Soo

2017-04-01

The Haeundae, located at the south eastern end of the Korean Peninsula, is a famous beach, which has an approximately 1.6 km long and 70 m wide coastline. The beach has been repeatedly eroded by the swell waves caused by typhoons in summer and high waves originating in the East Sea in winter. The Korean government conducted beach restoration projects including beach nourishment (620,000 m3) and construction of two submerged breakwaters near both ends of the beach. To prevent the beach erosion and to support the beach restoration project, the Korean government initiated a R&D project, the development of coastal erosion control technology since 2013. As a part of the project, we have been measuring waves and currents at a water depth of 22 m, 1.8 km away from the beach using an acoustic wave and current meter (AWAC) continuously for more than three years; we have also measured waves and currents intensively near the surf-zone in summer and winter. In this study, a numerical simulation using a wave and current coupled model (ROMS-SWAN) was conducted for determining the wave-induced current considering seasonal swell waves (Hs : 2.5 m, Tp: 12 s) and for better understanding of the coastal process near the surf-zone in Haeundae. By comparing the measured and simulated results, we found that cross-shore current during summer is mainly caused by the eddy produced by the wave-induced current near the beach, which in turn, is generated by the strong waves coming from the SSW and S directions. During other seasons, longshore wave-induced current is produced by the swell waves coming from the E and ESE directions. The longshore current heading west toward Dong-Back Island, west end of the beach, during all the seasons and eddy current toward Mipo-Port, east end of the beach, in summer which is well matched with the observed residual current. The wave-induced current with long-term measurement data is incorporated in simulation of sediment transport modeling for developing coastal erosion control system in Haeundae.

Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12.

PubMed

Chung, Brile; Esmaeili, Ali A; Gopalakrishna-Pillai, Sailesh; Murad, John P; Andersen, Emily S; Kumar Reddy, Naveen; Srinivasan, Gayathri; Armstrong, Brian; Chu, Caleb; Kim, Young; Tong, Tommy; Waisman, James; Yim, John H; Badie, Behnam; Lee, Peter P

2017-01-01

The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast. To further understand the interplay between cancer cells and cancer-associated fibroblasts from each site, we developed three-dimensional organoids composed of patient-derived primary or brain metastasis cancer cells with matching cancer-associated fibroblasts. Three-dimensional CAF aggregates generated from brain metastasis promote migration of cancer cells more effectively than cancer-associated fibroblast aggregates derived from primary tumor or normal breast stromal cells. Treatment with a CXCR4 antagonist and/or CXCL16 neutralizing antibody, alone or in combination, significantly inhibited migration of cancer cells to brain metastatic cancer-associated fibroblast aggregates. These results demonstrate that human brain metastasis cancer-associated fibroblasts potently attract breast cancer cells via chemokines CXCL12 and CXCL16, and blocking CXCR6-CXCL16/CXCR4-CXCL12 receptor-ligand interactions may be an effective therapy for preventing breast cancer brain metastasis.

PD-L1 expression is associated with p16INK4A expression in non-oropharyngeal head and neck squamous cell carcinoma

PubMed Central

Chen, San-Chi; Chang, Peter Mu-Hsin; Wang, Hsiao-Jung; Tai, Shyh-Kuan; Chu, Pen-Yuan; Yang, Muh-Hwa

2018-01-01

PD-L1 expression is critical in helping tumor cells evade the immune system. However, the level of PD-L1 expression in non-oropharyngeal head and neck squamous cell carcinoma (non-OPHNSCC) and its association with patient prognosis remains unclear. A retrospective clinicopathological analysis was performed on 106 patients with non-OPHNSCC diagnosed between 2007 and 2014. In the current study, tissue arrays from paraffin-embedded non-OPHNSCC samples obtained from patients were constructed, and PD-L1 and p16INK4A expression were determined using immunohistochemistry. Systemic inflammatory factors, including C-reactive protein, serum white blood cell, neutrophil, monocyte and lymphocyte counts were also analyzed. The current study demonstrated that PD-L1 was overexpressed in 32.1% (34/106) and p16INK4A in 20.8% (22/106) of patients. The expression of PD-L1 was associated with p16INK4A expression (P<0.01) but was not associated with levels of systemic inflammatory factors. Tumor stage was determined to be a significant prognostic value (stage I/II vs. III/IV, P=0.03), however, PD-L1, p16INK4A or other clinicopathological factors were not. The current study identified an association between PD-L1 and p16INK4A expression in non-OPHNSCC. This may facilitate the development of anti-PD1/PDL1 therapies to treat patients with head and neck cancer. PMID:29434933

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function.

PubMed

Ardell, Jeffrey L; Rajendran, Pradeep S; Nier, Heath A; KenKnight, Bruce H; Armour, J Andrew

2015-11-15

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. Copyright © 2015 the American Physiological Society.

Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function

PubMed Central

Rajendran, Pradeep S.; Nier, Heath A.; KenKnight, Bruce H.; Armour, J. Andrew

2015-01-01

Using vagus nerve stimulation (VNS), we sought to determine the contribution of vagal afferents to efferent control of cardiac function. In anesthetized dogs, the right and left cervical vagosympathetic trunks were stimulated in the intact state, following ipsilateral or contralateral vagus nerve transection (VNTx), and then following bilateral VNTx. Stimulations were performed at currents from 0.25 to 4.0 mA, frequencies from 2 to 30 Hz, and a 500-μs pulse width. Right or left VNS evoked significantly greater current- and frequency-dependent suppression of chronotropic, inotropic, and lusitropic function subsequent to sequential VNTx. Bradycardia threshold was defined as the current first required for a 5% decrease in heart rate. The threshold for the right vs. left vagus-induced bradycardia in the intact state (2.91 ± 0.18 and 3.47 ± 0.20 mA, respectively) decreased significantly with right VNTx (1.69 ± 0.17 mA for right and 3.04 ± 0.27 mA for left) and decreased further following bilateral VNTx (1.29 ± 0.16 mA for right and 1.74 ± 0.19 mA for left). Similar effects were observed following left VNTx. The thresholds for afferent-mediated effects on cardiac parameters were 0.62 ± 0.04 and 0.65 ± 0.06 mA with right and left VNS, respectively, and were reflected primarily as augmentation. Afferent-mediated tachycardias were maintained following β-blockade but were eliminated by VNTx. The increased effectiveness and decrease in bradycardia threshold with sequential VNTx suggest that 1) vagal afferents inhibit centrally mediated parasympathetic efferent outflow and 2) the ipsilateral and contralateral vagi exert a substantial buffering capacity. The intact threshold reflects the interaction between multiple levels of the cardiac neural hierarchy. PMID:26371171

Time-dependent photon heat transport through a mesoscopic Josephson device

NASA Astrophysics Data System (ADS)

Lu, Wen-Ting; Zhao, Hong-Kang

2017-02-01

The time-oscillating photon heat current through a dc voltage biased mesoscopic Josephson Junction (MJJ) has been investigated by employing the nonequilibrium Green's function approach. The Landauer-like formula of photon heat current has been derived in both of the Fourier space and its time-oscillating versions, where Coulomb interaction, self inductance, and magnetic flux take effective roles. Nonlinear behaviors are exhibited in the photon heat current due to the quantum nature of MJJ and applied external dc voltage. The magnitude of heat current decreases with increasing the external bias voltage, and subtle oscillation structures appear as the superposition of different photon heat branches. The overall period of heat current with respect to time is not affected by Coulomb interaction, however, the magnitude and phase of it vary considerably by changing the Coulomb interaction.

Energetic Particle Sounding of the Magnetopause Deformed by Hot Flow Anomaly

NASA Astrophysics Data System (ADS)

Zhao, L.; Zong, Q.; Zhang, H.

2017-12-01

Hot flow anomalies (HFAs), which are frequently observed near Earth's bow shock, are phenomena resulting from the interaction between interplanetary discontinuities and Earth's bow shock. Such transient phenomena upstream the bow shock can cause significant deformation of the bow shock and the magnetosphere, generating traveling convection vortices, field-aligned currents, and ULF waves in the Earth's magnetosphere. A large HFA was observed by MMS on November 19, 2015, lasting about 16 minutes. In this study, energetic particle sounding method with high time resolution (150 ms) Fast Plasma Investigation (FPI) data is used to determine the deformed magnetopause distances, orientations, and structures in the interval when MMS pass through the deformed magnetopause. The energetic particle sounding result from single MMS satellite for every moment in the interval when the distance from the magnetopause to the satellite is less than two proton gyro radii shows the profile of the deformed magnetopause.

Recent activity in the moon; Proceedings of the Special Symposium, Houston, Tex., March 16, 1976

NASA Technical Reports Server (NTRS)

Runcorn, S. K.; Oreilly, W.; Srnka, L. J.

1977-01-01

The papers review evidence for recent activity within the moon as manifested by lunar grid system, transient phenomena, moonquakes, and episodic emissions of radiogenic gases. Topics include a survey of lunar transient phenomena, possible causes of such phenomena, evidence that high-frequency seismic events may be shallow moonquakes, lunar seismicity and tectonics, a hypothesis on the nature of sites of lunar gas venting, and a search for sporadic gas emissions from the moon. Other contributions discuss the release of radiogenic argon-40 from the moon, radon-222 emission as an indicator of current activity on the moon, upper limits to gas emission from sites of lunar transient phenomena, physical processes that could produce transient changes on the lunar surface, critical-velocity gas-plasma interaction as a mechanism for lunar transient phenomena, and tidal triggering of moonquakes, transient phenomena, and radiogenic-gas emissions.

A novel reconfigurable electromagnetically induced transparency based on S-PINs

NASA Astrophysics Data System (ADS)

Xue, Feng; Liu, Shao-Bin; Zhang, Hai-Feng; Wen, Yong-Diao; Kong, Xiang-Kun; Li, Hai-Ming

2018-02-01

In this paper, a tunable electromagnetically induced transparency (EIT) based on S-PINs is theoretically analyzed. Unit cell of the structure consists of a cutwire (CW), split ring resonator (SRR), and solid state plasma (SS plasma) patches which are composed of S-PIN array. The destructive interference between the CW and SRR results in a narrowband transparency window accompanied with strong phase dispersion. The proposed design can obtain a tunable EIT with different frequencies range from 12.8 GHz to 16.5 GHz in a simple method by switching these S-PINs on or off selectively. The related parameters of the S-PIN such as the size, carrier concentration, and volt-ampere characteristics have been studied theoretically. The interaction and coupling between two resonators are investigated in detail by the analysis of the current distribution and E-field strength as well. The research results provide an effective way to realize reconfigurable compact slow-light devices.

Business intelligence from social media: a study from the VAST Box Office Challenge.

PubMed

Lu, Yafeng; Wang, Feng; Maciejewski, Ross

2014-01-01

With over 16 million tweets per hour, 600 new blog posts per minute, and 400 million active users on Facebook, businesses have begun searching for ways to turn real-time consumer-based posts into actionable intelligence. The goal is to extract information from this noisy, unstructured data and use it for trend analysis and prediction. Current practices support the idea that visual analytics (VA) can help enable the effective analysis of such data. However, empirical evidence demonstrating the effectiveness of a VA solution is still lacking. A proposed VA toolkit extracts data from Bitly and Twitter to predict movie revenue and ratings. Results from the 2013 VAST Box Office Challenge demonstrate the benefit of an interactive environment for predictive analysis, compared to a purely statistical modeling approach. The VA approach used by the toolkit is generalizable to other domains involving social media data, such as sales forecasting and advertisement analysis.

Correlation of particle-induced displacement damage in silicon

NASA Astrophysics Data System (ADS)

Summers, G. P.; Dale, C. J.; Burke, E. A.; Wolicki, E. A.; Marshall, P. W.

1987-12-01

The effects of displacement damage caused in several types of silicon bipolar transistors by protons, deuterons, helium ions, and by 1-MeV-equivalent neutrons are considered. Measurements are compared to calculations of the nonionizing energy deposition in silicon as a function of particle type and energy. Measurements were made of displacement damage factors for 2N2222A and 2N2907A switching transistors, and for 2N3055, 2N6678, and 2N6547 power transistors, as a function of collector current using 3.7-175-MeV protons, 4.3-37-MeV deuterons, and 16.8-65-MeV helium ions. Long-term ionization effects on the value of the displacement damage factors were taken into account. In calculating the energy dependence of the nonionizing energy deposition, Rutherford, nuclear elastic, and nuclear inelastic interactions, and Lindhard energy partition were considered.

Parental Displacement and Adolescent Suicidality: Exploring the Role of Failed Belonging

PubMed Central

Timmons, Katherine A.; Selby, Edward A.; Lewinsohn, Peter M.; Joiner, Thomas E.

2011-01-01

Prior studies have demonstrated that events causing displacement from parents—such as parental death, abandonment of the adolescent, or divorce—represent a risk factor for adolescent suicide, but research to date has not established a theoretical model explaining the association between parental displacement and adolescent suicidal behavior. The current studies examined the construct of failed belonging proposed by the interpersonal theory of suicide as one factor that may link parental displacement with adolescent suicide. Study 1 found that low levels of belonging mediated the association between parental displacement and adolescent suicide attempts in a large urban community sample of older adolescents between the ages of 18 and 23. In Study 2, parental displacement interacted with low belonging to predict suicide attempts, such that adolescents (average age 16.6 years; (SD = 1.2) who experienced both displacement and low levels of belonging had the highest risk for suicide. PMID:22023272

Parental displacement and adolescent suicidality: exploring the role of failed belonging.

PubMed

Timmons, Katherine A; Selby, Edward A; Lewinsohn, Peter M; Joiner, Thomas E

2011-01-01

Prior studies have demonstrated that events causing displacement from parents--such as parental death, abandonment of the adolescent, or divorce--represent a risk factor for adolescent suicide, but research to date has not established a theoretical model explaining the association between parental displacement and adolescent suicidal behavior. The current studies examined the construct of failed belonging proposed by the interpersonal theory of suicide as one factor that may link parental displacement with adolescent suicide. Study 1 found that low levels of belonging mediated the association between parental displacement and adolescent suicide attempts in a large, urban community sample of older adolescents between the ages of 18 and 23. In Study 2, parental displacement interacted with low belonging to predict suicide attempts, such that adolescents (average age = 16.6 years; SD = 1.2) who experienced both displacement and low levels of belonging had the highest risk for suicide.

The bar PANDA Barrel-TOF Detector at FAIR

NASA Astrophysics Data System (ADS)

Zimmermann, S.; Suzuki, K.; Steinschaden, D.; Chirita, M.; Ahmed, G.; Dutta, K.; Kalita, K.; Lehmann, A.; Böhm, M.; Schwarz, K.; Orth, H.; Brinkmann, K.-Th.

2017-08-01

The barrel-Time-of-Flight subdetector is one of the outer layers of the multi-layer design of the \\panda target spectrometer. It is designed with a minimal material budget in mind mainly consisting of 90×30×5 mm3 thin plastic scintillator tiles read out on each end by a serial connection of 4 SiPMs. 120 such tiles are placed on 16 2460 × 180 mm2 PCB boards forming a barrel covering an azimuthal angle from 22.5o to 150o. The detector is designed to achieve a time resolution below σ< 100 ps which allows to distinguish events in the constant stream of hits, as well as particle identification below the Cherenkov threshold via the time-of-flight; simultaneously providing the interaction times of events. The current prototype achieved a time resolution of ~54 ps, well below the design goal.

Attachment representations and anxiety: differential relationships among mothers of sexually abused and comparison girls.

PubMed

Kim, Kihyun; Trickett, Penelope K; Putnam, Frank W

2011-02-01

The present study sought to document an example of how childhood sexual abuse and attachment representation interact while contributing to the trait anxiety of nonoffending mothers following the disclosure of their daughters' sexual abuse. The study sample consisted of 57 ethnically diverse mothers of sexually abused girls aged 6 to 16 and 47 mothers of comparison girls who were matched with the abused girls on age, socioeconomic status, and family constellation. Results indicate that the mothers' representations of past attachment relationships with their own fathers were differentially related to their current attachment styles, depending on their daughters' childhood sexual abuse status. The representation of past attachment relationships with peers had both main and protective effects on the mothers' trait anxiety symptoms. The relevance of attachment perspectives to adjustment among these mothers and intergenerational process in childhood sexual abuse are discussed, and implications for future research and clinical practices are identified.

NASA Tech Briefs, January 2001. Volume 25, No. 1

NASA Technical Reports Server (NTRS)

2001-01-01

The topics include: 1) A "Model" of Interactive Engineering; 2) Feature Section: Communications Technology; 3) lnReview; 4) Application Briefs; 5) Submillimeter-Wave Image Sensor; 6) Ultrasonic/Sonic Drill/Corers With Integrated Sensors; 7) Normally Closed, Piezoelectrically Actuated Microvalve; 8) Magnetostrictively Actuated Valves for Cryosurgical Probes; 9) Remote Sensing of Electric Fields in Clouds; 10) Wireless-Communication Headset Subsystem To Enhance Signaling; 11) Power Amplifier With 9 to 13 dB of Gain From 65 to 146 GHz; 12) Humidity Interlock for Protecting a Cooled Laser Crystal; 13) A Lightweight Ambulatory Physiological Monitoring System; 14) Improvements in a Lightning-Measuring Instrument; 15) Broad-Band, Noninvasive Radio-Frequency Current Probe; 16) Web-Based Technology Distributes Lean Models; 17) Software Guides Aeroelastic-Systems Design; and 18) Postprocessing Software for Micromechanics Analysis Code. A Photonics West 2001 Preview Tech Brief supplement to this January 2001 issue is also included.

The Expanding Family of Virophages.

PubMed

Bekliz, Meriem; Colson, Philippe; La Scola, Bernard

2016-11-23

Virophages replicate with giant viruses in the same eukaryotic cells. They are a major component of the specific mobilome of mimiviruses. Since their discovery in 2008, five other representatives have been isolated, 18 new genomes have been described, two of which being nearly completely sequenced, and they have been classified in a new viral family, Lavidaviridae . Virophages are small viruses with approximately 35-74 nm large icosahedral capsids and 17-29 kbp large double-stranded DNA genomes with 16-34 genes, among which a very small set is shared with giant viruses. Virophages have been isolated or detected in various locations and in a broad range of habitats worldwide, including the deep ocean and inland. Humans, therefore, could be commonly exposed to virophages, although currently limited evidence exists of their presence in humans based on serology and metagenomics. The distribution of virophages, the consequences of their infection and the interactions with their giant viral hosts within eukaryotic cells deserve further research.

MIrExpress: A Database for Gene Coexpression Correlation in Immune Cells Based on Mutual Information and Pearson Correlation

PubMed Central

Wang, Luman; Mo, Qiaochu; Wang, Jianxin

2015-01-01

Most current gene coexpression databases support the analysis for linear correlation of gene pairs, but not nonlinear correlation of them, which hinders precisely evaluating the gene-gene coexpression strengths. Here, we report a new database, MIrExpress, which takes advantage of the information theory, as well as the Pearson linear correlation method, to measure the linear correlation, nonlinear correlation, and their hybrid of cell-specific gene coexpressions in immune cells. For a given gene pair or probe set pair input by web users, both mutual information (MI) and Pearson correlation coefficient (r) are calculated, and several corresponding values are reported to reflect their coexpression correlation nature, including MI and r values, their respective rank orderings, their rank comparison, and their hybrid correlation value. Furthermore, for a given gene, the top 10 most relevant genes to it are displayed with the MI, r, or their hybrid perspective, respectively. Currently, the database totally includes 16 human cell groups, involving 20,283 human genes. The expression data and the calculated correlation results from the database are interactively accessible on the web page and can be implemented for other related applications and researches. PMID:26881263

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

Anderson, D. R.; Hellier, C.; Smalley, B.

We report the discovery of the transiting giant planet WASP-17b, the least-dense planet currently known. It is 1.6 Saturn masses, but 1.5-2 Jupiter radii, giving a density of 6%-14% that of Jupiter. WASP-17b is in a 3.7 day orbit around a sub-solar metallicity, V = 11.6, F6 star. Preliminary detection of the Rossiter-McLaughlin effect suggests that WASP-17b is in a retrograde orbit (lambda approx -150{sup 0}), indicative of a violent history involving planet-planet or star-planet scattering. WASP-17b's bloated radius could be due to tidal heating resulting from recent or ongoing tidal circularization of an eccentric orbit, such as the highlymore » eccentric orbits that typically result from scattering interactions. It will thus be important to determine more precisely the current orbital eccentricity by further high-precision radial velocity measurements or by timing the secondary eclipse, both to reduce the uncertainty on the planet's radius and to test tidal-heating models. Owing to its low surface gravity, WASP-17b's atmosphere has the largest scale height of any known planet, making it a good target for transmission spectroscopy.« less

The Medical Library Association Benchmarking Network: results.

PubMed

Dudden, Rosalind Farnam; Corcoran, Kate; Kaplan, Janice; Magouirk, Jeff; Rand, Debra C; Smith, Bernie Todd

2006-04-01

This article presents some limited results from the Medical Library Association (MLA) Benchmarking Network survey conducted in 2002. Other uses of the data are also presented. After several years of development and testing, a Web-based survey opened for data input in December 2001. Three hundred eighty-five MLA members entered data on the size of their institutions and the activities of their libraries. The data from 344 hospital libraries were edited and selected for reporting in aggregate tables and on an interactive site in the Members-Only area of MLANET. The data represent a 16% to 23% return rate and have a 95% confidence level. Specific questions can be answered using the reports. The data can be used to review internal processes, perform outcomes benchmarking, retest a hypothesis, refute a previous survey findings, or develop library standards. The data can be used to compare to current surveys or look for trends by comparing the data to past surveys. The impact of this project on MLA will reach into areas of research and advocacy. The data will be useful in the everyday working of small health sciences libraries as well as provide concrete data on the current practices of health sciences libraries.

The Medical Library Association Benchmarking Network: results*

PubMed Central

Dudden, Rosalind Farnam; Corcoran, Kate; Kaplan, Janice; Magouirk, Jeff; Rand, Debra C.; Smith, Bernie Todd

2006-01-01

Objective: This article presents some limited results from the Medical Library Association (MLA) Benchmarking Network survey conducted in 2002. Other uses of the data are also presented. Methods: After several years of development and testing, a Web-based survey opened for data input in December 2001. Three hundred eighty-five MLA members entered data on the size of their institutions and the activities of their libraries. The data from 344 hospital libraries were edited and selected for reporting in aggregate tables and on an interactive site in the Members-Only area of MLANET. The data represent a 16% to 23% return rate and have a 95% confidence level. Results: Specific questions can be answered using the reports. The data can be used to review internal processes, perform outcomes benchmarking, retest a hypothesis, refute a previous survey findings, or develop library standards. The data can be used to compare to current surveys or look for trends by comparing the data to past surveys. Conclusions: The impact of this project on MLA will reach into areas of research and advocacy. The data will be useful in the everyday working of small health sciences libraries as well as provide concrete data on the current practices of health sciences libraries. PMID:16636703

MIrExpress: A Database for Gene Coexpression Correlation in Immune Cells Based on Mutual Information and Pearson Correlation.

PubMed

Wang, Luman; Mo, Qiaochu; Wang, Jianxin

2015-01-01

Most current gene coexpression databases support the analysis for linear correlation of gene pairs, but not nonlinear correlation of them, which hinders precisely evaluating the gene-gene coexpression strengths. Here, we report a new database, MIrExpress, which takes advantage of the information theory, as well as the Pearson linear correlation method, to measure the linear correlation, nonlinear correlation, and their hybrid of cell-specific gene coexpressions in immune cells. For a given gene pair or probe set pair input by web users, both mutual information (MI) and Pearson correlation coefficient (r) are calculated, and several corresponding values are reported to reflect their coexpression correlation nature, including MI and r values, their respective rank orderings, their rank comparison, and their hybrid correlation value. Furthermore, for a given gene, the top 10 most relevant genes to it are displayed with the MI, r, or their hybrid perspective, respectively. Currently, the database totally includes 16 human cell groups, involving 20,283 human genes. The expression data and the calculated correlation results from the database are interactively accessible on the web page and can be implemented for other related applications and researches.

Polarization Transfer in the Reaction 4He($$\\vec{v}$$,e'$$\\vec{p}$$) 3H in the Quasielastic Scattering Region

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

Dieterich, Sonja

2002-05-01

There has been a longstanding issue concerning possible nucleon modifications in a (dense) nuclear medium. Polarization transfer data for exclusive quasielastic electron scattering are a sensitive to the ratio of the electric and magnetic nucleon form factors in the medium. Although proper interpretation of the results requires accounting for such effects as final state interactions and meson exchange currents, their effect on polarization transfer is predicted to be small. Studies of model dependencies, e.g., the off-shell current operator and spinor distortions, have been done. Final results of a measurement of polarization transfer in the 4He(more » $$\\vec{v}$$,e'$$\\vec{p}$$) 3H reaction will be discussed. The experiments were carried out at MAMI, Mainz at a Q 2 of 0.4 GeV 2 and at the Thomas Jefferson Lab, Newport News, Virginia at the Q 2 values 0.5, 1.0, 1.6 and 2.6 GeV 2. Measured values of the transferred and induced polarization are compared with various theoretical calculations. The experiment showed a difference between the fully relativistic model with may indicate medium modifications of the form factor.« less

Identification of pleasant, neutral, and unpleasant odors in schizophrenia

PubMed Central

Kamath, Vidyulata; Turetsky, Bruce I.; Moberg, Paul J.

2010-01-01

Recent work on odor hedonics in schizophrenia has indicated that patients display abnormalities in hedonic judgments of odors in comparison to healthy comparison participants. In the current study, identification accuracy for pleasant, neutral, and unpleasant odors in individuals with schizophrenia and healthy controls was examined. Thirty-three schizophrenia patients (63% male) and thirty-one healthy volunteers (65% male) were recruited. The groups were well matched on age, sex, and smoking status. Participants were administered the University of Pennsylvania Smell Identification Test, which was subsequently divided into 16 pleasant, 15 neutral, and 9 unpleasant items. Analysis of identification z-scores for pleasant, neutral, and unpleasant odors revealed a significant diagnosis by valence interaction. Post-hoc analysis revealed that schizophrenia participants made more identification errors on pleasant and neutral odors compared to healthy controls, with no differences observed for unpleasant odors. No effect was seen for sex. The findings from the current investigation suggest that odor identification accuracy in patients is influenced by odor valence. This pattern of results parallels a growing body of literature indicating that patients display aberrant pleasantness ratings for pleasant odors and highlights the need for additional research on the influence of odor valence on olfactory identification performance in individuals with schizophrenia. PMID:21239063

Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery.

PubMed

Merritt, Sonia R; Velasquez, Gia; von Recum, Horst A

2013-11-01

The aim of this study is to demonstrate a drug delivery system with the capacity to adjust the release of mitomycin C (MMC), based on polymer composition, and inhibit fibroblast proliferation to a better effect than is currently used in glaucoma filtration surgery. The polymer used in this work is made from the oligosaccharide cyclodextrin, from which others and we have demonstrated adjustable release of small molecule drugs due to specific molecular interactions or "affinity" between drug and the cyclodextrin polymer. To adjust release rate, cyclodextrin polymers were synthesized in either dimethylformamide (DMF) or dimethyl sulfoxide, (DMSO) at a crosslinking ratio of 1:0.16 or 1:0:32 (molecule of glucose: molecule of crosslinker). The polymers were then loaded with mitomycin C, dried, and release evaluated in a physiological environment. Drug release was determined by visible spectroscopy. Released aliquots of mitomycin C were incubated with 3T3 fibroblast cells to determine cytotoxic or inhibitory effect through a cell proliferation assay. We show that by using affinity between drug and polymer, we can adjust MMC release rates to be slower and more sustained than from conventional, diffusion-only polymers, for both the DMF polymers (p = 0.00526) and the DMSO polymers (p = 0.0113). The incorporated and released MMC maintains inhibition of fibroblast proliferation much longer than is possible with a one-time application. Affinity polymers with 1:0.16 and 1:0.32 crosslink ratio showed significant inhibition of proliferation for up to 100 h (p = 0.018 and p = 0.014 respectively). The use of our controlled drug delivery technology applied after surgery could have a greater therapeutic impact than the current one-time applications of MMC. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery

PubMed Central

Merritt, Sonia R.; Velasquez, Gia; von Recum, Horst A.

2016-01-01

The aim of this study is to demonstrate a drug delivery system with the capacity to adjust the release of mitomycin C (MMC), based on polymer composition, and inhibit fibroblast proliferation to a better effect than is currently used in glaucoma filtration surgery. The polymer used in this work is made from the oligosaccharide cyclodextrin, from which others and we have demonstrated adjustable release of small molecule drugs due to specific molecular interactions or “affinity” between drug and the cyclodextrin polymer. To adjust release rate, cyclodextrin polymers were synthesized in either dimethylformamide (DMF) or dimethyl sulfoxide, (DMSO) at a crosslinking ratio of 1:0.16 or 1:0:32 (molecule of glucose: molecule of crosslinker). The polymers were then loaded with mitomycin C, dried, and release evaluated in a physiological environment. Drug release was determined by visible spectroscopy. Released aliquots of mitomycin C were incubated with 3T3 fibroblast cells to determine cytotoxic or inhibitory effect through a cell proliferation assay. We show that by using affinity between drug and polymer, we can adjust MMC release rates to be slower and more sustained than from conventional, diffusion-only polymers, for both the DMF polymers (p = 0.00526) and the DMSO polymers (p = 0.0113). The incorporated and released MMC maintains inhibition of fibroblast proliferation much longer than is possible with a one-time application. Affinity polymers with 1:0.16 and 1:0.32 crosslink ratio showed significant inhibition of proliferation for up to 100 h (p = 0.018 and p = 0.014 respectively). The use of our controlled drug delivery technology applied after surgery could have a greater therapeutic impact than the current one-time applications of MMC. PMID:23911951

Response of the Milky Way's disc to the Large Magellanic Cloud in a first infall scenario

NASA Astrophysics Data System (ADS)

Laporte, Chervin F. P.; Gómez, Facundo A.; Besla, Gurtina; Johnston, Kathryn V.; Garavito-Camargo, Nicolas

2018-01-01

We present N-body and hydrodynamical simulations of the response of the Milky Way's baryonic disc to the presence of the Large Magellanic Cloud during a first infall scenario. For a fiducial Galactic model reproducing the gross properties of the Galaxy, we explore a set of six initial conditions for the Large Magellanic Cloud (LMC) of varying mass which all evolve to fit the measured constraints on its current position and velocity with respect to the Galactic Centre. We find that the LMC can produce strong disturbances - warping of the stellar and gaseous discs - in the Galaxy, without violating constraints from the phase-space distribution of stars in the Solar Neighbourhood. All models correctly reproduce the phases of the warp and its antisymmetrical shape about the disc's mid-plane. If the warp is due to the LMC alone, then the largest mass model is favoured (2.5 × 1011 M⊙). Still, some quantitative discrepancies remain, including deficits in height of ΔZ = 0.7 kpc at R = 22 kpc and ΔZ = 0.7 kpc at R = 16 kpc. This suggests that even higher infall masses for the LMC's halo are allowed by the data. A comparison with the vertical perturbations induced by a heavy Sagittarius dSph model (1011 M⊙) suggest that positive interference with the LMC warp is expected at R = 16 kpc. We conclude that the vertical structure of the Galactic disc beyond the Solar Neighbourhood may jointly be shaped by its most massive satellites. As such, the current structure of the Milky Way suggests we are seeing the process of disc heating by satellite interactions in action.

Bacterial Community Sstructure and Novel Species of Magnetotactic Bacteria in Sediments from a Seamount in the Mariana Volcanic Arc

NASA Astrophysics Data System (ADS)

PAN, H.; LIU, J.; Zhang, W.; Xiao, T.; Wu, L. F.

2017-12-01

Seamounts are unique ecosystems where undersea mountains rise abruptly from the sea floor and interact dynamically with underwater currents, creating peculiar biological habitats with various microbial community structures. Certain bacteria associated with seamounts form conspicuous extracellular iron oxide structures, including encrusted stalks, flattened bifurcating tubes, and filamentous sheaths. To extend knowledge of seamount microorganisms we performed a systematic analysis of the population composition and occurrence of live magnetotactic bacteria (MTB) in sediments of a seamount in the Mariana volcanic arc. Proteobacteria dominated at 13 stations, and were the second in abundance to members of the Firmicutes at a deep station on a steep slope facing the Yap-Mariana trench. We found MTB that synthesize intracellular iron-oxide nanocrystals in biogenic sediments at all 14 stations, at seawater depths ranging from 238 to 2023 m. A novel flagellar apparatus, and the most complex yet reported, was observed in magnetotactic cocci; it comprises one or two bundles of 19 flagella arranged in a 3:4:5:4:3 array. Phylogenetic analysis of 16S rRNA gene sequences identified 16 novel species of MTB specific to this seamount. The geographic properties at the various stations on the seamount appear to be important in shaping the microbial community structure.

Qualification of the flight-critical AFTI/F-16 digital flight control system. [Advanced Fighter Technology Integration

NASA Technical Reports Server (NTRS)

Mackall, D. A.; Ishmael, S. D.; Regenie, V. A.

1983-01-01

Qualification considerations for assuring the safety of a life-critical digital flight control system include four major areas: systems interactions, verification, validation, and configuration control. The AFTI/F-16 design, development, and qualification illustrate these considerations. In this paper, qualification concepts, procedures, and methodologies are discussed and illustrated through specific examples.

The effects of drought and herbivory on plant–herbivore interactions across 16 soybean genotypes in a field experiment

USDA-ARS?s Scientific Manuscript database

As the Earth’s climate continues to change, drought and insect population outbreaks are predicted to increase in many parts of the world. It is therefore important to understand how changes in such abiotic and biotic stressors might impact agroecosystems. 16 soybean genotypes were tested in a field ...

Spin alignment of ρ0 mesons produced in antineutrino and neutrino neon charged-current interactions

NASA Astrophysics Data System (ADS)

Wittek, W.; Guy, J.; Adeholz, M.; Allport, P.; Baton, J. P.; Berggren, M.; Bertrand, D.; Brisson, V.; Bullock, F. W.; Burkot, W.; Calicchio, M.; Clayton, E. F.; Coghen, T.; Cooper-Sarkar, A. M.; Erriquez, O.; Fitch, P. J.; Fogli-Muciaccia, M. T.; Hulth, P. O.; Jones, G. T.; Kasper, P.; Klein, H.; Marage, P.; Middleton, R. P.; Miller, D. B.; Mobayyen, M. M.; Morrison, D. R. O.; Neveu, M.; O'Neale, S. W.; Parker, M. A.; Petiau, P.; Sacton, J.; Sansum, R. A.; Schmitz, N.; Simopoulou, E.; Vallee, C.; Varvell, K.; Vayaki, A.; Venus, W.; Wachsmuth, H.; Wells, J.

1987-03-01

In a bubble chamber experiment with BEBC the spin alignment parameter η=1/2 (2ϱ00 - ϱ11 - ϱ-1-1) is measured for ϱ0 mesons produced in deep inelastic charged-current antineutrino and neutrono interactions on neon. In the current fragmentation region η is found to be ηv=0.48+/-0.27 (stat.)+/-0.15 (syst.) for vNe and ηv=0.12+/-0.20 (stat.)+/-0.10 (syst.) for vNe interactions Present address: University College London, London WC1E 6BT, UK.

Comparisons of neutrino event generators from an oscillation-experiment perspective

NASA Astrophysics Data System (ADS)

Mayer, Nathan

2015-05-01

Monte Carlo generators are crucial to the analysis of high energy physics data, ideally giving a baseline comparison between the state-of-art theoretical models and experimental data. Presented here is a comparison between three of final state distributions from the GENIE, Neut, NUANCE, and NuWro neutrino Monte Carlo event generators. The final state distributions chosen for comparison are: the electromagnetic energy fraction in neutral current interactions, the energy of the leading π0 vs. the scattering angle for neutral current interactions, and the muon energy vs. scattering angle of νµ charged current interactions.

Weak Interaction Models with New Quarks and Right-handed Currents

DOE R&D Accomplishments Database

Wilczek, F. A.; Zee, A.; Kingsley, R. L.; Treiman, S. B.

1975-06-01

We discuss various weak interaction issues for a general class of models within the SU(2) x U(1) gauge theory framework, with special emphasis on the effects of right-handed, charged currents and of quarks bearing new quantum numbers. In particular we consider the restrictions on model building which are imposed by the small KL - KS mass difference and by the .I = = rule; and we classify various possibilities for neutral current interactions and, in the case of heavy mesons with new quantum numbers, various possibilities for mixing effects analogous to KL - KS mixing.

Nonlinear interaction of the Tsugaru Warm Current and tide in the Tsugaru Strait

NASA Astrophysics Data System (ADS)

Wada, Ryota; Waseda, Takuji; Nanjo, Hirotada

2012-06-01

The Tsugaru Strait, which connects the Sea of Japan with the Pacific Ocean, is characterized by the eastward Tsugaru Warm Current (TWC) and oscillating tidal currents of similar magnitude. A 15-day current observation was conducted in one of the two narrow channels in the strait, at the northwest tip of the Shimokita Peninsula. The observation revealed that the spectral energy of the semidiurnal current exceeds that of the diurnal current, contrary to the conventional view. The Tsugaru Strait regional model was developed to study the mechanism of this spectral energy reversal (140-141.5° E, 40.4-42.6° N, 500 m grid resolution). At the eastern and western open boundaries, the model was driven by the constant Tsugaru warm current and tidal elevation, which was adjusted by comparing the model with tidal gauge observations within the channel. The relative magnitude of the spectral energies differed from that of the observation when the model was driven by tide only. However, the spectral energy levels were reversed when the model was driven by both tide and current. The nonlinear interaction of periodic tidal currents and the steady TWC was explained by the vorticity equation, which describes the production and advection of residual currents from tidal currents. According to the model results, flow separation and advection of vorticity by the TWC was the most prominent factor in this phenomenon. Because of the strong nonlinearities, flow separation around the headland occurred during the tidal period with dominant current magnitude and furnished the main difference between the diurnal and semidiurnal interactions. These phenomena were enhanced by the complex topography, and demonstrate the importance of scale interaction, especially when developing high-resolution regional models.

Maternal Resolution of Grief After Preterm Birth: Implications for Infant Attachment Security

PubMed Central

Clements, Melissa; Poehlmann, Julie

2011-01-01

OBJECTIVE: This study explored the association between mothers' unresolved grief regarding their infant's preterm birth and infant-mother attachment security. We hypothesized that mothers with unresolved grief would be more likely to have insecurely attached infants at 16 months and that this association would be partially mediated by maternal interaction quality. METHODS: This longitudinal study focused on 74 preterm infants (age of <36 weeks) and their mothers who were part of a larger study of high-risk infants. The present analysis included assessment of neonatal and socioeconomic risks at NICU discharge; maternal depression, Reaction to Preterm Birth Interview findings, and quality of parenting at a postterm age of 9 months; and infant-mother attachment at postterm age of 16 months. Associations among findings of grief resolution with the Reaction to Preterm Birth Interview, quality of parenting interactions, and attachment security were explored by using relative risk ratios and logistic and multivariate regression models. RESULTS: The relative risk of developing insecure attachment when mothers had unresolved grief was 1.59 (95% confidence interval: 1.03–2.44). Controlling for covariates (adjusted odds ratio: 2.94), maternal feelings of resolved grief regarding the preterm birth experience were associated with secure infant-mother attachment at 16 months. Maternal grief resolution and interaction quality were independent predictors of attachment security. CONCLUSION: Maternal grief resolution regarding the experience of preterm birth and the quality of maternal interactions have important implications for emerging attachment security for infants born prematurely. PMID:21242223

Maternal resolution of grief after preterm birth: implications for infant attachment security.

PubMed

Shah, Prachi E; Clements, Melissa; Poehlmann, Julie

2011-02-01

This study explored the association between mothers' unresolved grief regarding their infant's preterm birth and infant-mother attachment security. We hypothesized that mothers with unresolved grief would be more likely to have insecurely attached infants at 16 months and that this association would be partially mediated by maternal interaction quality. This longitudinal study focused on 74 preterm infants (age of <36 weeks) and their mothers who were part of a larger study of high-risk infants. The present analysis included assessment of neonatal and socioeconomic risks at NICU discharge; maternal depression, Reaction to Preterm Birth Interview findings, and quality of parenting at a postterm age of 9 months; and infant-mother attachment at postterm age of 16 months. Associations among findings of grief resolution with the Reaction to Preterm Birth Interview, quality of parenting interactions, and attachment security were explored by using relative risk ratios and logistic and multivariate regression models. The relative risk of developing insecure attachment when mothers had unresolved grief was 1.59 (95% confidence interval: 1.03-2.44). Controlling for covariates (adjusted odds ratio: 2.94), maternal feelings of resolved grief regarding the preterm birth experience were associated with secure infant-mother attachment at 16 months. Maternal grief resolution and interaction quality were independent predictors of attachment security. Maternal grief resolution regarding the experience of preterm birth and the quality of maternal interactions have important implications for emerging attachment security for infants born prematurely.

Loading capacity and interaction of DNA binding on catanionic vesicles with different cationic surfactants.

PubMed

Xu, Lu; Chen, Jingfei; Feng, Lei; Dong, Shuli; Hao, Jingcheng

2014-12-07

Cationic and anionic (catanionic) vesicles were constructed from the mixtures of sodium laurate (SL) and alkyltrimethylammonium bromide (CnTAB, n = 12, 14, and 16) and were used to control the loading capacity of DNA. The binding saturation point (BSP) of DNA to catanionic vesicles increases with the chain length of cationic surfactants, which is at 1.0, 1.3 and 1.5 for CnTAB with n = 12, 14, and 16, respectively. Our measurements showed that the loading capacity and affinity of DNA can be controlled by catanionic vesicles. It increases with the chain length of cationic surfactants. Because of a large reduction in surface charge density, catanionic vesicles are prone to undergo re-aggregation or fusion with the addition of DNA. DNA molecules can still maintain original coil state during the interaction with catanionic CnTAL vesicles. (1)H NMR data reveals that the obvious dissociation of anionic ions, L(-), from catanionic C14TAL vesicles is due to the interaction with DNA; however, this phenomenon cannot be observed in C12TAB-SL vesicles. Agarose gel electrophoresis (AGE) results demonstrate that the electrostatic interaction between the two oppositely charged cationic and anionic surfactants is stronger than that between DNA and cationic surfactant, CnTAB (n = 12, 14, and 16). Not only is the dissociation of L(-) simply determined by the charge competition, but it also depends largely on the variations in the surface charge density as well as the cationic and anionic surfactant competing ability in geometry configuration of catanionic vesicles. The complicated interaction between DNA and catanionic vesicles induces the deformation of cationic vesicles. Our results should provide clear guidance for choosing more proper vectors for DNA delivery and gene therapy in cell experiments.

Identification of Parent-Child Interaction Characteristics of High and Low Achieving Elementary Students.

ERIC Educational Resources Information Center

Portes, Pedro R.; And Others

The present study was designed to identify parent-child interaction patterns that might differentiate bright from below average elementary students in order to test the hypothesis that environmental processes related to regulation of executive processes influence both children's learning and developmental level. Thirty-two mother-child dyads (16…

Children's Interaction and Lexical Acquisition in Text-Based Online Chat

ERIC Educational Resources Information Center

Coyle, Yvette; Reverte Prieto, Maria José

2017-01-01

This is an empirical study in which we explore child foreign language learners' interactional strategy use, uptake, and lexical acquisition in synchronous computer-mediated communication (SCMC). The study was carried out with 16 10-year-old Spanish English as a foreign language learners paired with age- and proficiency-matched English native…

Genotype × Environment Interaction in Smoking Behaviors: A Systematic Review.

PubMed

Do, Elizabeth K; Maes, Hermine H

2017-04-01

There has been rapid growth in research exploring gene-environment interaction (G×E) contributing to smoking behaviors. Yet, no systematic review exists to date. This article aims to review evidence on the contribution of G×E to the risk of smoking. Through a search of electronic databases (ie, Google Scholar, PubMed, ScienceDirect, and Elsevier) up until May 2014, 16 studies of G×E focused on smoking behaviors were identified. These studies were compared in terms of: research design and sample studied, measure of smoking behavior and environments used, genes explored, and G×E in relation to these factors. Thirteen of 16 studies (81.2%) found at least one significant G×E association. Wide variation in analytic methods was found across studies, especially with respect to the phenotypes of interest, environmental measures used, and tests conducted to estimate G×E. Heterogeneity across studies made it difficult to compare findings and evaluate the strength of evidence for G×E. G×E research on smoking contains studies that are methodologically different, making it difficult to assess the current state of the evidence. To decrease heterogeneity, we offer recommendations related to: (1) choice of measurement for environmental variables, (2) testing and reporting of main and interaction effects, (3) treatment of covariates, (4) reporting gene-environment correlation, and (5) conducting sensitivity analyses and checking for scaling artifacts. Continued study is needed to identify mechanisms by which genes and environmental factors combine to influence smoking behaviors. No comprehensive review of G×E studies of smoking behavior has previously been published. The present article seeks to fill this gap by providing a comprehensive review of: how G×E has been defined, how twin and molecular genetic methodologies have been used to test for G×E, and which genes and environmental factors are associated with smoking behaviors. Variations in methodological approaches make it difficult to interpret and summarize findings, so recommendations for future research are provided as a means to more easily compare and replicate findings across studies. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Albrecht, Simon; Winn, Joshua N.; Johnson, John A.

We provide evidence that the obliquities of stars with close-in giant planets were initially nearly random, and that the low obliquities that are often observed are a consequence of star-planet tidal interactions. The evidence is based on 14 new measurements of the Rossiter-McLaughlin effect (for the systems HAT-P-6, HAT-P-7, HAT-P-16, HAT-P-24, HAT-P-32, HAT-P-34, WASP-12, WASP-16, WASP-18, WASP-19, WASP-26, WASP-31, Gl 436, and Kepler-8), as well as a critical review of previous observations. The low-obliquity (well-aligned) systems are those for which the expected tidal timescale is short, and likewise the high-obliquity (misaligned and retrograde) systems are those for which the expectedmore » timescale is long. At face value, this finding indicates that the origin of hot Jupiters involves dynamical interactions like planet-planet interactions or the Kozai effect that tilt their orbits rather than inspiraling due to interaction with a protoplanetary disk. We discuss the status of this hypothesis and the observations that are needed for a more definitive conclusion.« less

Zwitterionic 4-bromo-6-meth-oxy-2-{[tris-(hy-droxy-meth-yl)methyl]-iminiumyl-meth-yl}phenolate: crystal structure and Hirshfeld surface analysis.

PubMed

Lee, See Mun; Lo, Kong Mun; Tan, Sang Loon; Tiekink, Edward R T

2016-08-01

In the solid state, the title compound, C12H16BrNO5 [systematic name: 4-bromo-2-((1E)-{[1,3-dihy-droxy-2-(hy-droxy-meth-yl)propan-2-yl]iminium-yl}meth-yl)-6-meth-oxy-benzen-1-olate], C12H16BrNO5, is found in the keto-amine tautomeric form, with an intra-molecular iminium-N-H⋯O(phenolate) hydrogen bond and an E conformation about the C=N bond. Both gauche (two) and anti relationships are found for the methyl-hydroxy groups. In the crystal, a supra-molecular layer in the bc plane is formed via hy-droxy-O-H⋯O(hy-droxy) and charge-assisted hy-droxy-O-H⋯O(phenolate) hydrogen-bonding inter-actions; various C-H⋯O inter-actions provide additional cohesion to the layers, which stack along the a axis with no directional inter-actions between them. A Hirshfeld surface analysis confirms the lack of specific inter-actions in the inter-layer region.

Ion irradiation induced effects and magnetization reversal mechanism in (Ni80Fe20)1-xCox nanowires and nanotubes

NASA Astrophysics Data System (ADS)

Ahmad, Naeem; Iqbal, Javed; Chen, J. Y.; Hussain, Asim; Shi, D. W.; Han, X. F.

2015-03-01

The effect of Co on the ferromagnetic characteristics of the Ni80Fe20 nanocylinders having zero magnetostriction and soft magnetic nature is an interesting field of research. The (Ni80Fe20)1-xCox nanocylinders have been prepared by electrodeposition into commercially available anodized aluminum oxide (AAO) nanoporous templates. The analysis of magnetization reversal from the angular dependence of coercivity has been studied in detail. This angular dependence of coercivity has shown a transition from curling to nucleation mode as a function of field angle for all (Ni80Fe20)1-xCox nanocylinders depending upon the critical angle. The shape anisotropy, dipole-dipole interactions, surface effects and magnetocrystalline anisotropy have been found to play an effective role for the spontaneous magnetization in nanowires and nanotubes. It has been interestingly observed that the magnetostatic interactions or dipole-dipole interactions are dominant in nanocylinders regardless of its geometry. Furthermore, the prepared samples have been irradiated with He2+ ions (energy E=2 MeV, fluence=1014 ions/cm2 and ion current=16 nA) at room temperature using a 5-UDH-2pelletron tandem accelerator. The irradiations have created defects and these defects have induced changes in magnetization as a result an increase in coercivity as function of the ion fluences is observed. Such kind of behavior in coercivity enhancement and magnetization reduction can also be attributed to the stress relaxation and percolation in nonuniform states of ferromagnetic alloys, respectively.

The Interactive Effect of Diabetes Family Conflict and Depression on Insulin Bolusing Behaviors for Youth.

PubMed

Maliszewski, Genevieve; Patton, Susana R; Midyett, L Kurt; Clements, Mark A

2017-05-01

Adherence to type 1 diabetes management declines as children enter adolescence. For youth, psychosocial variables including mood and interpersonal relationships play a large role in diabetes maintenance. The current study assessed the unique and interactive roles diabetes family conflict and depression have on insulin bolusing behaviors for youth ages 10-16 years. Ninety-one youth-parent dyads completed a survey assessing family conflict and depression. Mean daily blood glucose levels, mealtime insulin bolus scores ( BOLUS), and glycated hemoglobin (HbA1c) were collected from the medical record as outcome variables. Parent-reported diabetes-related family conflict and youths' endorsed depression both significantly predicted insulin bolusing behavior, R 2 = .13, F(2, 88) = 6.66, P < .05. The interaction of diabetes family conflict and youth depression played a significant role in youths' bolusing behaviors, above and beyond that which was predicted by conflict and depression separately, R 2 = .18, F change (1, 87) = 4.63, P < .05. BOLUS was negatively related to youths' hemoglobin A1c, r = -.556, P < .001 and mean daily blood glucose levels, r = -.428, P < .001. Among depressed youth, mealtime insulin BOLUS scores declined with greater diabetes-related family conflict, while there was no change in BOLUS scores among depressed youth living in families reporting less conflict. Findings underscore the importance of screening for depression and family conflict in youth experiencing or at risk for poor adherence to mealtime insulin and higher HbA1c levels.

In vitro magnetic resonance imaging evaluation of ossicular implants at 3 T.

PubMed

Shellock, Frank G; Meepos, Lauren N; Stapleton, Matthew R; Valencerina, Sam

2012-07-01

Ossicular implants made from metallic materials may be acceptable or pose hazards for patients referred for magnetic resonance imaging (MRI) examinations, depending on the outcome of proper MRI testing procedures. Using a 3-T MR system, 2 ossicular implants were tested for magnetic field interactions, heating, and artifacts. Two different ossicular implants (Stainless Steel/Fluoroplastic Sanna-Type Piston [6 mm in length] and the Offset ALTO Total Prosthesis [15 mm in length, titanium/silicone]; Grace Medical, Memphis, TN, USA) were selected for testing, which represented the largest metallic mass and materials with the highest magnetic susceptibilities, with the intent of applying the MRI findings to other ossicular implants. The implants were evaluated at 3-T for magnetic field interactions, heating, and artifacts using standard previously described techniques. Each ossicular implant showed relatively minor magnetic field interactions that will not be associated with movement in situ. Heating was not excessive (highest temperature change, ≤ 1.6°C; background temperature change, 1.5°C). Artifacts, although relatively small, may create issues for diagnostic imaging if the area of interest is in the same area or close to these ossicular implants. The results of this investigation demonstrated that it would be acceptable (i.e., "MR conditional" using current terminology) for patients with these ossicular implants to undergo MRI examinations at 3 T or less. In consideration of the materials and dimensions of the implants that underwent testing, these findings pertain to many other similar ossicular implants from the same manufacturer.

Wastewater and Hazardous Waste Survey, Homestead AFB Florida.

DTIC Science & Technology

1988-03-01

tank into the sanitary sewer. 16. Bilge waste from the Water Survival School is currently placed in 55-gallon drums and stored on site. At the time...plant. W0’I; • ,. =% . Fiue5. AGE Accumulation Site , 30 7. A disposal contract for waste bilge water is needed for the Water Survival School. Currently...eliminate all pesticide wastes from S this shop. 16. The Water Survival School can possibly eliminate bilge water waste by having Civil Engineering

Differential state-dependent modification of rat Na{sub v}1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin

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

He, Bingjun; Soderlund, David M., E-mail: dms6@cornell.edu

2011-12-15

We expressed rat Na{sub v}1.6 sodium channels in combination with the rat {beta}1 and {beta}2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Na{sub v}1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent 'late' currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady-state inactivation. Maximal shifts in activation, determined from the voltagemore » dependence of the pyrethroid-induced late and tail currents, were {approx} 25 mV for tefluthrin and {approx} 20 mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of {approx} 5-10 mV in the voltage dependence of steady-state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Na{sub v}1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7 Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by {approx} 2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Na{sub v}1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Na{sub v}1.6 channels in HEK293 cells differ from the effects of these compounds on Na{sub v}1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment. -- Highlights: Black-Right-Pointing-Pointer We expressed rat Na{sub v}1.6 voltage-gated sodium channels in HEK293 cells. Black-Right-Pointing-Pointer Tefluthrin and deltamethrin caused resting modification of Na{sub v}1.6 channels. Black-Right-Pointing-Pointer Only deltamethrin exhibited use-dependent enhancement of modification. Black-Right-Pointing-Pointer State-dependent effects of pyrethroids are influenced by the cellular context. Black-Right-Pointing-Pointer Channels in HEK293 cells exhibit properties similar to native neuronal channels.« less

Pressure and heat flux results from the space shuttle/external fuel tank interaction test at Mach numbers 16 and 19

NASA Technical Reports Server (NTRS)

Brewer, E. B.; Haberman, D. R.

1974-01-01

Heat transfer rates and pressures were measured on a 0.0175-scale model of the space shuttle external tank (ET), model MCR0200. Tests were conducted with the ET model separately and while mated with a 0.0175-scale model of the orbiter, model 21-OT (Grumman). The tests were conducted in the AEDC-VKF Hypervelocity Wind Tunnel (F) at Mach numbers 16 and 19. The primary data consisted of the interaction heating rates experienced by the ET while mated with the orbiter in the flight configuration. Data were taken for a range of Reynolds numbers from 50,000 to 65,000 under laminar flow conditions.

Testing hadronic interactions at ultrahigh energies with air showers measured by the Pierre Auger Observatory

DOE PAGES

Aab, A.; Abreu, P.; Aglietta, M.; ...

2016-10-31

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6–16 EeV (E CM = 110–170 TeV), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. As a result, the average hadronic shower is 1.33±0.16 (1.61±0.21) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide

NASA Astrophysics Data System (ADS)

Bellucci, Luca; Ardèvol, Albert; Parrinello, Michele; Lutz, Helmut; Lu, Hao; Weidner, Tobias; Corni, Stefano

2016-04-01

Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution.Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution. Electronic supplementary information (ESI) available: Representative structures for the most populated conformational structures of Aβ16-22 on bulk and on the metal surface. Normalized distribution of the variable s defined as the sum of internal dihedral angles of the peptide in solution and at the gold/water interface. See DOI: 10.1039/C6NR01539E

Interactions between cadmium and decabrominated diphenyl ether on blood cells count in rats-Multiple factorial regression analysis.

PubMed

Curcic, Marijana; Buha, Aleksandra; Stankovic, Sanja; Milovanovic, Vesna; Bulat, Zorica; Đukić-Ćosić, Danijela; Antonijević, Evica; Vučinić, Slavica; Matović, Vesna; Antonijevic, Biljana

2017-02-01

The objective of this study was to assess toxicity of Cd and BDE-209 mixture on haematological parameters in subacutely exposed rats and to determine the presence and type of interactions between these two chemicals using multiple factorial regression analysis. Furthermore, for the assessment of interaction type, an isobologram based methodology was applied and compared with multiple factorial regression analysis. Chemicals were given by oral gavage to the male Wistar rats weighing 200-240g for 28days. Animals were divided in 16 groups (8/group): control vehiculum group, three groups of rats were treated with 2.5, 7.5 or 15mg Cd/kg/day. These doses were chosen on the bases of literature data and reflect relatively high Cd environmental exposure, three groups of rats were treated with 1000, 2000 or 4000mg BDE-209/kg/bw/day, doses proved to induce toxic effects in rats. Furthermore, nine groups of animals were treated with different mixtures of Cd and BDE-209 containing doses of Cd and BDE-209 stated above. Blood samples were taken at the end of experiment and red blood cells, white blood cells and platelets counts were determined. For interaction assessment multiple factorial regression analysis and fitted isobologram approach were used. In this study, we focused on multiple factorial regression analysis as a method for interaction assessment. We also investigated the interactions between Cd and BDE-209 by the derived model for the description of the obtained fitted isobologram curves. Current study indicated that co-exposure to Cd and BDE-209 can result in significant decrease in RBC count, increase in WBC count and decrease in PLT count, when compared with controls. Multiple factorial regression analysis used for the assessment of interactions type between Cd and BDE-209 indicated synergism for the effect on RBC count and no interactions i.e. additivity for the effects on WBC and PLT counts. On the other hand, isobologram based approach showed slight antagonism for the effects on RBC and WBC while no interactions were proved for the joint effect on PLT count. These results confirm that the assessment of interactions between chemicals in the mixture greatly depends on the concept or method used for this evaluation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Polarization of Λ hyperons produced inclusively in v p andbar v p charged current interactions

NASA Astrophysics Data System (ADS)

Jones, G. T.; Kennedy, B. W.; O'Neale, S. W.; Böckmann, K.; Gebel, W.; Geich-Gimbel, C.; Nellen, B.; Cooper-Sarkar, A. M.; Grant, A.; Klein, H.; Morrison, D. R. O.; Schmid, P.; Wachsmuth, H.; Barnham, K. W. J.; Clayton, E. F.; Miller, D. B.; Mobayyen, M. M.; Villalobos-Baillie, O.; Aderholz, M.; Deck, L.; Schmitz, N.; Settles, R.; Wernhard, K. L.; Wittek, W.; Corrigan, G.; Myatt, G.; Radojicic, D.; Saitta, B.; Wells, J.

1985-03-01

Lambda hyperons from v p andbar v p charged current interactions have been analysed for polarization. A significant polarization is observed for Λ particles in the quasi-elastic region for both types of interactions. Part of this polarization is due to the decay of highly polarized Σ(1385) resonances. The results are compared with simple predictions of the quark parton model.

Spin-orbit-torque-induced skyrmion dynamics for different types of spin-orbit coupling

NASA Astrophysics Data System (ADS)

Lee, Seung-Jae; Kim, Kyoung-Whan; Lee, Hyun-Woo; Lee, Kyung-Jin

2018-06-01

We investigate current-induced skyrmion dynamics in the presence of Dzyaloshinskii-Moriya interaction and spin-orbit spin-transfer torque corresponding to various types of spin-orbit coupling. We determine the symmetries of Dzyaloshinskii-Moriya interaction and spin-orbit spin-transfer torque based on linear spin-orbit coupling model. We find that like interfacial Dzyaloshinskii-Moriya interaction (Rashba spin-orbit coupling) and bulk Dzyaloshinskii-Moriya interaction (Weyl spin-orbit coupling), Dresselhaus spin-orbit coupling also has a possibility for stabilizing skyrmion and current-induced skyrmion dynamics.

Probing the interaction between the histone methyltransferase/deacetylase subunit RBBP4/7 and the transcription factor BCL11A in epigenetic complexes.

PubMed

Moody, Rebecca Reed; Lo, Miao-Chia; Meagher, Jennifer L; Lin, Chang-Ching; Stevers, Nicholas O; Tinsley, Samantha L; Jung, Inkyung; Matvekas, Aleksas; Stuckey, Jeanne A; Sun, Duxin

2018-02-09

The transcription factor BCL11A has recently been reported to be a driving force in triple-negative breast cancer (TNBC), contributing to the maintenance of a chemoresistant breast cancer stem cell (BCSC) population. Although BCL11A was shown to suppress γ-globin and p21 and to induce MDM2 expression in the hematopoietic system, its downstream targets in TNBC are still unclear. For its role in transcriptional repression, BCL11A was found to interact with several corepressor complexes; however, the mechanisms underlying these interactions remain unknown. Here, we reveal that BCL11A interacts with histone methyltransferase (PRC2) and histone deacetylase (NuRD and SIN3A) complexes through their common subunit, RBBP4/7. In fluorescence polarization assays, we show that BCL11A competes with histone H3 for binding to the negatively charged top face of RBBP4. To define that interaction, we solved the crystal structure of RBBP4 in complex with an N-terminal peptide of BCL11A (residues 2-16, BCL11A(2-16)). The crystal structure identifies novel interactions between BCL11A and the side of the β-propeller of RBBP4 that are not seen with histone H3. We next show that BCL11A(2-16) pulls down RBBP4, RBBP7, and other components of PRC2, NuRD, and SIN3A from the cell lysate of the TNBC cell line SUM149. Furthermore, we demonstrate the therapeutic potential of targeting the RBBP4-BCL11A binding by showing that a BCL11A peptide can decrease aldehyde dehydrogenase-positive BCSCs and mammosphere formation capacity in SUM149. Together, our findings have uncovered a previously unidentified mechanism that BCL11A may use to recruit epigenetic complexes to regulate transcription and promote tumorigenesis. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation

PubMed Central

Fantini, Jacques; Yahi, Nouara; Garmy, Nicolas

2013-01-01

Age-related alterations of membrane lipids in brain cell membranes together with high blood cholesterol are considered as major risk factors for Alzheimer's disease. Yet the molecular mechanisms by which these factors increase Alzheimer's risk are mostly unknown. In lipid raft domains of the plasma membrane, neurotoxic Alzheimer's beta-amyloid (Abeta) peptides interact with both cholesterol and ganglioside GM1. Recent data also suggested that cholesterol could stimulate the binding of Abeta to GM1 through conformational modulation of the ganglioside headgroup. Here we used a combination of physicochemical and molecular modeling approaches to decipher the mechanisms of cholesterol-assisted binding of Abeta to GM1. With the aim of decoupling the effect of cholesterol on GM1 from direct Abeta-cholesterol interactions, we designed a minimal peptide (Abeta5-16) containing the GM1-binding domain but lacking the amino acid residues involved in cholesterol recognition. Using the Langmuir technique, we showed that cholesterol (but not phosphatidylcholine or sphingomyelin) significantly accelerates the interaction of Abeta5-16 with GM1. Molecular dynamics simulations suggested that Abeta5-16 interacts with a cholesterol-stabilized dimer of GM1. The main structural effect of cholesterol is to establish a hydrogen-bond between its own OH group and the glycosidic-bond linking ceramide to the glycone part of GM1, thereby inducing a tilt in the glycolipid headgroup. This fine conformational tuning stabilizes the active conformation of the GM1 dimer whose headgroups, oriented in two opposite directions, form a chalice-shaped receptacle for Abeta. These data give new mechanistic insights into the stimulatory effect of cholesterol on Abeta/GM1 interactions. They also support the emerging concept that cholesterol is a universal modulator of protein-glycolipid interactions in the broader context of membrane recognition processes. PMID:23772214

Phylogeny of the Defined Murine Microbiota: Altered Schaedler Flora

PubMed Central

Dewhirst, Floyd E.; Chien, Chih-Ching; Paster, Bruce J.; Ericson, Rebecca L.; Orcutt, Roger P.; Schauer, David B.; Fox, James G.

1999-01-01

The “altered Schaedler flora” (ASF) was developed for colonizing germfree rodents with a standardized microbiota. The purpose of this study was to identify each of the eight ASF strains by 16S rRNA sequence analysis. Three strains were previously identified as Lactobacillus acidophilus (strain ASF 360), Lactobacillus salivarius (strain ASF 361), and Bacteroides distasonis (strain ASF 519) based on phenotypic criteria. 16S rRNA analysis indicated that each of the strains differed from its presumptive identity. The 16S rRNA sequence of strain ASF 361 is essentially identical to the 16S rRNA sequences of the type strains of Lactobacillus murinis and Lactobacillus animalis (both isolated from mice), and all of these strains probably belong to a single species. Strain ASF 360 is a novel lactobacillus that clusters with L. acidophilus and Lactobacillus lactis. Strain ASF 519 falls into an unnamed genus containing [Bacteroides] distasonis, [Bacteroides] merdae, [Bacteroides] forsythus, and CDC group DF-3. This unnamed genus is in the Cytophaga-Flavobacterium-Bacteroides phylum and is most closely related to the genus Porphyromonas. The spiral-shaped strain, strain ASF 457, is in the Flexistipes phylum and exhibits sequence identity with rodent isolates of Robertson. The remaining four ASF strains, which are extremely oxygen-sensitive fusiform bacteria, group phylogenetically with the low-G+C-content gram-positive bacteria (Firmicutes, Bacillus-Clostridium group). ASF 356, ASF 492, and ASF 502 fall into Clostridium cluster XIV of Collins et al. Morphologically, ASF 492 resembles members of this cluster, Roseburia cecicola, and Eubacterium plexicaudatum. The 16S rRNA sequence of ASF 492 is identical to that of E. plexicaudatum. Since the type strain and other viable original isolates of E. plexicaudatum have been lost, strain ASF 492 is a candidate for a neotype strain. Strain ASF 500 branches deeply in the low-G+C-content gram-positive phylogenetic tree but is not closely related to any organisms whose 16S rRNA sequences are currently in the GenBank database. The 16S rRNA sequence information determined in the present study should allow rapid identification of ASF strains and should permit detailed analysis of the interactions of ASF organisms during development of intestinal disease in mice that are coinfected with a variety of pathogenic microorganisms. PMID:10427008

Potassium and ANO1/TMEM16A chloride channel profiles distinguish atypical and typical smooth muscle cells from interstitial cells in the mouse renal pelvis

PubMed Central

Iqbal, Javed; Tonta, Mary A; Mitsui, Retsu; Li, Qun; Kett, Michelle; Li, Jinhua; Parkington, Helena C; Hashitani, Hikaru; Lang, Richard J

2012-01-01

BACKGROUND AND PURPOSE Although atypical smooth muscle cells (SMCs) in the proximal renal pelvis are thought to generate the pacemaker signals that drive pyeloureteric peristalsis, their location and electrical properties remain obscure. EXPERIMENTAL APPROACH Standard patch clamp, intracellular microelectrode and immunohistochemistry techniques were used. To unequivocally identify SMCs, transgenic mice with enhanced yellow fluorescent protein (eYFP) expressed in cells containing α-smooth muscle actin (α-SMA) were sometimes used. KEY RESULTS Atypical SMCs were distinguished from typical SMCs by the absence of both a transient 4-aminopyridine-sensitive K+ current (IKA) and spontaneous transient outward currents (STOCs) upon the opening of large-conductance Ca2+-activated K+ (BK) channels. Many typical SMCs displayed a slowly activating, slowly decaying Cl- current blocked by niflumic acid (NFA). Immunostaining for KV4.3 and ANO1/ TMEM16A Cl- channel subunits co-localized with α-SMA immunoreactive product predominately in the distal renal pelvis. Atypical SMCs fired spontaneous inward currents that were either selective for Cl- and blocked by NFA, or cation-selective and blocked by La3+. α-SMA- interstitial cells (ICs) were distinguished by the presence of a Xe991-sensitive KV7 current, BK channel STOCs and Cl- selective, NFA-sensitive spontaneous transient inward currents (STICs). Intense ANO1/ TMEM16A and KV7.5 immunostaining was present in Kit-α-SMA- ICs in the suburothelial and adventitial regions of the renal pelvis. CONCLUSIONS AND IMPLICATIONS We conclude that KV4.3+α-SMA+ SMCs are typical SMCs that facilitate muscle wall contraction, that ANO1/ TMEM16A and KV7.5 immunoreactivity may be selective markers of Kit- ICs and that atypical SMCs which discharge spontaneous inward currents are the pelviureteric pacemakers. PMID:22014103

Quantum thermal diode based on two interacting spinlike systems under different excitations.

PubMed

Ordonez-Miranda, Jose; Ezzahri, Younès; Joulain, Karl

2017-02-01

We demonstrate that two interacting spinlike systems characterized by different excitation frequencies and coupled to a thermal bath each, can be used as a quantum thermal diode capable of efficiently rectifying the heat current. This is done by deriving analytical expressions for both the heat current and rectification factor of the diode, based on the solution of a master equation for the density matrix. Higher rectification factors are obtained for lower heat currents, whose magnitude takes their maximum values for a given interaction coupling proportional to the temperature of the hotter thermal bath. It is shown that the rectification ability of the diode increases with the excitation frequencies difference, which drives the asymmetry of the heat current, when the temperatures of the thermal baths are inverted. Furthermore, explicit conditions for the optimization of the rectification factor and heat current are explicitly found.