2018-01-01
Presence of multiple copies of the microtubule-binding NDC80 complex is an evolutionary conserved feature of kinetochores, points of attachment of chromosomes to spindle microtubules. This may enable multivalent attachments to microtubules, with implications that remain unexplored. Using recombinant human kinetochore components, we show that while single NDC80 complexes do not track depolymerizing microtubules, reconstituted particles containing the NDC80 receptor CENP-T bound to three or more NDC80 complexes do so effectively, as expected for a kinetochore force coupler. To study multivalency systematically, we engineered modules allowing incremental addition of NDC80 complexes. The modules’ residence time on microtubules increased exponentially with the number of NDC80 complexes. Modules with two or more complexes tracked depolymerizing microtubules with increasing efficiencies, and stalled and rescued microtubule depolymerization in a force-dependent manner when conjugated to cargo. Our observations indicate that NDC80, rather than through biased diffusion, tracks depolymerizing microtubules by harnessing force generated during microtubule disassembly. PMID:29629870
Zelter, Alex; Riffle, Michael; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.
2018-01-01
Accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore–microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex–microtubule interaction is sufficiently strong to make a significant contribution to kinetochore–microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phosphoregulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Cross-linking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together, our results indicate that the Ska complex can directly strengthen the kinetochore–microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule. PMID:29487209
Purification and characterisation of the fission yeast Ndc80 complex.
Matsuo, Yuzy; Maurer, Sebastian P; Surrey, Thomas; Toda, Takashi
2017-07-01
The Ndc80 complex is a conserved outer kinetochore protein complex consisting of Ndc80 (Hec1), Nuf2, Spc24 and Spc25. This complex comprises a major, if not the sole, platform with which the plus ends of the spindle microtubules directly interact. In fission yeast, several studies indicate that multiple microtubule-associated proteins including the Dis1/chTOG microtubule polymerase and the Mal3/EB1 microtubule plus-end tracking protein directly or indirectly bind Ndc80, thereby ensuring stable kinetochore-microtubule attachment. However, the purification of the Ndc80 complex from this yeast has not been achieved, which hampers the in-depth investigation as to how the outer kinetochore attaches to the plus end of the spindle microtubule. Here we report the two-step purification of the fission yeast Ndc80 holo complex from bacteria. First, we purified separately two sub-complexes consisting of Ndc80-Nuf2 and Spc24-Spc25. Then, these two sub-complexes were mixed and applied to size-exclusion chromatography. The reconstituted Ndc80 holo complex is composed of four subunits with equal stoichiometry. The complex possesses microtubule-binding activity, and Total Internal Reflection Fluorescence (TIRF)-microscopy assays show that the complex binds the microtubule lattice. Interestingly, unlike the human complex, the fission yeast complex does not track depolymerising microtubule ends. Further analysis shows that under physiological ionic conditions, the Ndc80 holo complex does not detectably bind Dis1, but instead it interacts with Mal3/EB1, by which the Ndc80 complex tracks the growing microtubule plus end. This result substantiates the notion that the Ndc80 complex plays a crucial role in establishment of the dynamic kinetochore-microtubule interface by cooperating with chTOG and EB1. Copyright © 2017 The Francis Crick Institute. Published by Elsevier Inc. All rights reserved.
Architecture and Flexibility of the Yeast Ndc80 Kinetochore Complex
Wang, Hong-Wei; Long, Sydney; Ciferri, Claudio; Westermann, Stefan; Drubin, David; Barnes, Georjana; Nogales, Eva
2008-01-01
Kinetochores mediate microtubule–chromosome attachment and ensure accurate segregation of sister chromatids. The highly conserved Ndc80 kinetochore complex makes direct contacts with the microtubule and is essential for spindle checkpoint signaling. It contains a long coiled-coil region with globular domains at each end involved in kinetochore localization and microtubule binding, respectively. We have directly visualized the architecture of the yeast Ndc80 complex and found a dramatic kink within the 560-Å coiled-coil rod located about 160 Å from the larger globular head. Comparison of our electron microscopy images to the structure of the human Ndc80 complex allowed us to position the kink proximal to the microtubule-binding end and to define the conformational range of the complex. The position of the kink coincides with a coiled-coil breaking region conserved across eukaryotes. We hypothesize that the kink in Ndc80 is essential for correct kinetochore geometry and could be part of a tension-sensing mechanism at the kinetochore. PMID:18793650
Zhang, Gang; Kelstrup, Christian D; Hu, Xiao-Wen; Kaas Hansen, Mathilde J; Singleton, Martin R; Olsen, Jesper V; Nilsson, Jakob
2012-07-01
The Ndc80 complex establishes end-on attachment of kinetochores to microtubules, which is essential for chromosome segregation. The Ndc80 subunit is characterized by an N-terminal region that binds directly to microtubules, and a long coiled-coil region that interacts with Nuf2. A loop region in Ndc80 that generates a kink in the structure disrupts the long coiled-coil region but the exact function of this loop, has until now, not been clear. Here we show that this loop region is essential for end-on attachment of kinetochores to microtubules in human cells. Cells expressing loop mutants of Ndc80 are unable to align the chromosomes, and stable kinetochore fibers are absent. Through quantitative mass spectrometry and immunofluorescence we found that the binding of the spindle and kinetochore associated (Ska) complex depends on the loop region, explaining why end-on attachment is defective. This underscores the importance of the Ndc80 loop region in coordinating chromosome segregation through the recruitment of specific proteins to the kinetochore.
Tien, Jerry F; Fong, Kimberly K; Umbreit, Neil T; Payen, Celia; Zelter, Alex; Asbury, Charles L; Dunham, Maitreya J; Davis, Trisha N
2013-09-01
During mitosis, kinetochores physically link chromosomes to the dynamic ends of spindle microtubules. This linkage depends on the Ndc80 complex, a conserved and essential microtubule-binding component of the kinetochore. As a member of the complex, the Ndc80 protein forms microtubule attachments through a calponin homology domain. Ndc80 is also required for recruiting other components to the kinetochore and responding to mitotic regulatory signals. While the calponin homology domain has been the focus of biochemical and structural characterization, the function of the remainder of Ndc80 is poorly understood. Here, we utilized a new approach that couples high-throughput sequencing to a saturating linker-scanning mutagenesis screen in Saccharomyces cerevisiae. We identified domains in previously uncharacterized regions of Ndc80 that are essential for its function in vivo. We show that a helical hairpin adjacent to the calponin homology domain influences microtubule binding by the complex. Furthermore, a mutation in this hairpin abolishes the ability of the Dam1 complex to strengthen microtubule attachments made by the Ndc80 complex. Finally, we defined a C-terminal segment of Ndc80 required for tetramerization of the Ndc80 complex in vivo. This unbiased mutagenesis approach can be generally applied to genes in S. cerevisiae to identify functional properties and domains.
The Ndc80 complex bridges two Dam1 complex rings
Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N
2017-01-01
Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital. DOI: http://dx.doi.org/10.7554/eLife.21069.001 PMID:28191870
Kudalkar, Emily M.; Scarborough, Emily A.; Umbreit, Neil T.; Zelter, Alex; Gestaut, Daniel R.; Riffle, Michael; Johnson, Richard S.; MacCoss, Michael J.; Asbury, Charles L.; Davis, Trisha N.
2015-01-01
Multiple protein subcomplexes of the kinetochore cooperate as a cohesive molecular unit that forms load-bearing microtubule attachments that drive mitotic chromosome movements. There is intriguing evidence suggesting that central kinetochore components influence kinetochore–microtubule attachment, but the mechanism remains unclear. Here, we find that the conserved Mis12/MIND (Mtw1, Nsl1, Nnf1, Dsn1) and Ndc80 (Ndc80, Nuf2, Spc24, Spc25) complexes are connected by an extensive network of contacts, each essential for viability in cells, and collectively able to withstand substantial tensile load. Using a single-molecule approach, we demonstrate that an individual MIND complex enhances the microtubule-binding affinity of a single Ndc80 complex by fourfold. MIND itself does not bind microtubules. Instead, MIND binds Ndc80 complex far from the microtubule-binding domain and confers increased microtubule interaction of the complex. In addition, MIND activation is redundant with the effects of a mutation in Ndc80 that might alter its ability to adopt a folded conformation. Together, our results suggest a previously unidentified mechanism for regulating microtubule binding of an outer kinetochore component by a central kinetochore complex. PMID:26430240
Molecular Analysis of Core Kinetochore Composition and Assembly in Drosophila melanogaster
Przewloka, Marcin R.; Archambault, Vincent; D'Avino, Pier Paolo; Lilley, Kathryn S.; Laue, Ernest D.; McAinsh, Andrew D.; Glover, David M.
2007-01-01
Background Kinetochores are large multiprotein complexes indispensable for proper chromosome segregation. Although Drosophila is a classical model organism for studies of chromosome segregation, little is known about the organization of its kinetochores. Methodology/Principal Findings We employed bioinformatics, proteomics and cell biology methods to identify and analyze the interaction network of Drosophila kinetochore proteins. We have shown that three Drosophila proteins highly diverged from human and yeast Ndc80, Nuf2 and Mis12 are indeed their orthologues. Affinity purification of these proteins from cultured Drosophila cells identified a further five interacting proteins with weak similarity to subunits of the SPC105/KNL-1, MIND/MIS12 and NDC80 kinetochore complexes together with known kinetochore associated proteins such as dynein/dynactin, spindle assembly checkpoint components and heterochromatin proteins. All eight kinetochore complex proteins were present at the kinetochore during mitosis and MIND/MIS12 complex proteins were also centromeric during interphase. Their down-regulation led to dramatic defects in chromosome congression/segregation frequently accompanied by mitotic spindle elongation. The systematic depletion of each individual protein allowed us to establish dependency relationships for their recruitment onto the kinetochore. This revealed the sequential recruitment of individual members of first, the MIND/MIS12 and then, NDC80 complex. Conclusions/Significance The Drosophila MIND/MIS12 and NDC80 complexes and the Spc105 protein, like their counterparts from other eukaryotic species, are essential for chromosome congression and segregation, but are highly diverged in sequence. Hierarchical dependence relationships of individual proteins regulate the assembly of Drosophila kinetochore complexes in a manner similar, but not identical, to other organisms. PMID:17534428
Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi
2016-01-01
The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1.
Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi
2016-01-01
ABSTRACT The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1. PMID:26900649
Holmström, Tim H; Rehnberg, Jonathan; Ahonen, Leena J; Kallio, Marko J
2009-06-01
Genomic stability depends on the normal function of the kinetochore, a multi-protein assemblage, which consists of over 80 molecules including both constitutive and transiently binding components. Information regarding the spatial-temporal assembly of kinetochore subcomplexes is often limited by technical difficulties in their isolation. To study kinetochore subcomplex formation, we targeted separately Hec1 and Spc24, two subunits of the Ndc80 kinetochore compilation, to the plasma membrane by fusing them with the amino-terminal palmitoylation and myristoylation (pm) sequence of the receptor tyrosine kinase Fyn. We found that in early mitotic cells, pm-GFP-Hec1 and pm-GFP-Spc24 fusion proteins localised to the plasma membrane and were able to recruit all subunits of the Ndc80 complex (Ndc80/Hec1, Nuf2, Spc24 and Spc25) to these foci. In interphase cells, only Hec1-Nuf2 and Spc24-Spc25 heterodimers accumulated to the plasma membrane foci. The results propose that the assembly of Ndc80 tetramer can take place outside of the kinetochore but requires co-factors that are only present in mitotic cells. These findings provide the first experimental evidence on the successful employment of the plasma membrane targeting technique in the study of kinetochore biochemistry.
Feijão, Tália; Afonso, Olga; Maia, André F; Sunkel, Claudio E
2013-10-01
Kinetochores bind spindle microtubules and also act as signaling centers that monitor this interaction. Defects in kinetochore assembly lead to chromosome missegregation and aneuploidy. The interaction between microtubules and chromosomes involves a conserved super-complex of proteins, known as the KNL1Mis12Ndc80 (KMN) network, composed by the KNL1 (Spc105), Mis12, and Ndc80 complexes. Previous studies indicate that all components of the network are required for kinetochore-microtubule attachment and all play relevant functions in chromosome congression, biorientation, and segregation. Here, we report a comparative study addressing the role of the different KMN components using dsRNA and in vivo fluorescence microscopy in Drosophila S2 cells allowing us to suggest that different KMN network components might perform different roles in chromosome segregation and the mitotic checkpoint signaling. Depletion of different components results in mostly lateral kinetochore-microtubule attachments that are relatively stable on depletion of Mis12 or Ndc80 but very unstable after Spc105 depletion. In vivo analysis on depletion of Mis12, Ndc80, and to some extent Spc105, shows that lateral kinetochore-microtubule interactions are still functional allowing poleward kinetochore movement. We also find that different KMN network components affect differently the localization of spindle assembly checkpoint (SAC) proteins at kinetochores. Depletion of Ndc80 and Spc105 abolishes the mitotic checkpoint, whereas depletion of Mis12 causes a delay in mitotic progression. Taken together, our results suggest that Mis12 and Ndc80 complexes help to properly orient microtubule attachment, whereas Spc105 plays a predominant role in the kinetochore-microtubule attachment as well as in the poleward movement of chromosomes, SAC response, and cell viability. Copyright © 2013 Wiley Periodicals, Inc.
Conserved tetramer junction in the kinetochore Ndc80 complex
Valverde, Roberto; Ingram, Jessica; Harrison, Stephen C.
2016-01-01
Summary The heterotetrameric Ndc80 complex establishes connectivity along the principal longitudinal axis of a kinetochore. Its two heterodimeric subcomplexes, each with a globular end and a coiled-coil shaft, connect end-to-end to create a ∼600 Å long rod spanning the gap from centromere-proximal structures to spindle microtubules. Neither subcomplex has a known function on its own, but the heterotetrameric organization and the characteristics of the junction are conserved from yeast to man. We have determined crystal structures of two shortened (“dwarf”) Ndc80 complexes that contain the full tetramer junction and both globular ends. The junction connects two α-helical coiled coils through regions of four-chain and three-chain overlap. The complexity of its structure depends on interactions among conserved amino-acid residues, suggesting a binding site for additional cellular factor(s) not yet identified. PMID:27851957
The Ndc80 complex targets Bod1 to human mitotic kinetochores
2017-01-01
Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis. Like PP2A-B56, Bod1 directly localizes to mitotic kinetochores and is required for correct segregation of mitotic chromosomes. In this report, we have probed the spatio-temporal regulation of Bod1 during mitotic progression. Kinetochore localization of Bod1 increases from nuclear envelope breakdown until metaphase. Phosphorylation of Bod1 at threonine 95 (T95), which increases Bod1's binding to and inhibition of PP2A-B56, peaks in prometaphase when PP2A-B56 localization to kinetochores is highest. We demonstrate here that kinetochore targeting of Bod1 depends on the outer kinetochore protein Ndc80 and not PP2A-B56. Crucially, Bod1 depletion functionally affects Ndc80 phosphorylation at the N-terminal serine 55 (S55), as well as a number of other phosphorylation sites within the outer kinetochore, including Knl1 at serine 24 and 60 (S24, S60), and threonine T943 and T1155 (T943, T1155). Therefore, Ndc80 recruits a phosphatase inhibitor to kinetochores which directly feeds forward to regulate Ndc80, and Knl1 phosphorylation, including sites that mediate the attachment of microtubules to kinetochores. PMID:29142109
Thapa, Kriti Shrestha; Oldani, Amanda; Pagliuca, Cinzia; De Wulf, Peter; Hazbun, Tony R
2015-05-01
Kinetochores are conserved protein complexes that bind the replicated chromosomes to the mitotic spindle and then direct their segregation. To better comprehend Saccharomyces cerevisiae kinetochore function, we dissected the phospho-regulated dynamic interaction between conserved kinetochore protein Cnn1(CENP-T), the centromere region, and the Ndc80 complex through the cell cycle. Cnn1 localizes to kinetochores at basal levels from G1 through metaphase but accumulates abruptly at anaphase onset. How Cnn1 is recruited and which activities regulate its dynamic localization are unclear. We show that Cnn1 harbors two kinetochore-localization activities: a C-terminal histone-fold domain (HFD) that associates with the centromere region and a N-terminal Spc24/Spc25 interaction sequence that mediates linkage to the microtubule-binding Ndc80 complex. We demonstrate that the established Ndc80 binding site in the N terminus of Cnn1, Cnn1(60-84), should be extended with flanking residues, Cnn1(25-91), to allow near maximal binding affinity to Ndc80. Cnn1 localization was proposed to depend on Mps1 kinase activity at Cnn1-S74, based on in vitro experiments demonstrating the Cnn1-Ndc80 complex interaction. We demonstrate that from G1 through metaphase, Cnn1 localizes via both its HFD and N-terminal Spc24/Spc25 interaction sequence, and deletion or mutation of either region results in anomalous Cnn1 kinetochore levels. At anaphase onset (when Mps1 activity decreases) Cnn1 becomes enriched mainly via the N-terminal Spc24/Spc25 interaction sequence. In sum, we provide the first in vivo evidence of Cnn1 preanaphase linkages with the kinetochore and enrichment of the linkages during anaphase. Copyright © 2015 by the Genetics Society of America.
D’Archivio, Simon
2017-01-01
Kinetochores are multiprotein complexes that couple eukaryotic chromosomes to the mitotic spindle to ensure proper segregation. The model for kinetochore assembly is conserved between humans and yeast, and homologues of several components are widely distributed in eukaryotes, but key components are absent in some lineages. The recent discovery in a lineage of protozoa called kinetoplastids of unconventional kinetochores with no apparent homology to model organisms suggests that more than one system for eukaryotic chromosome segregation may exist. In this study, we report a new family of proteins distantly related to outer kinetochore proteins Ndc80 and Nuf2. The family member in kinetoplastids, KKT-interacting protein 1 (KKIP1), associates with the kinetochore, and its depletion causes severe defects in karyokinesis, loss of individual chromosomes, and gross defects in spindle assembly or stability. Immunopurification of KKIP1 from stabilized kinetochores identifies six further components, which form part of a trypanosome outer kinetochore complex. These findings suggest that kinetochores in organisms such as kinetoplastids are built from a divergent, but not ancestrally distinct, set of components and that Ndc80/Nuf2-like proteins are universal in eukaryotic division. PMID:28034897
Xu, Wei; Ren, Ya-Nan; Xie, Miao; Zhou, Lin-Xia; Zheng, Yue-Qing
2018-03-28
A new series of uranium coordination polymers have been hydrothermally synthesized by using 1,4-naphthalene dicarboxylic acid (H 2 NDC), namely, (H 3 O) 2 [(UO 2 ) 2 (NDC) 3 ]·H 2 O (1), (H 2 -bpp)[(UO 2 ) 2 (NDC) 3 ]·EtOH·5H 2 O (2), (H 2 -bpe) 2/2 [(UO 2 ) 2 (NDC) 3 ]·EtOH (3), (H 2 -bpp)[(UO 2 ) 2 (NDC) 3 ]·5H 2 O (4), (H 2 -bpp)[(UO 2 )(HNDC)(NDC)] 2 ·2H 2 O (5), and (H 2 -bpy)[(UO 2 )(NDC) 2 ] (6) [bpp = 1,3-di(4-pyridyl) propane, bpe = 4,4'-vinylenedipyridine, bpy = 4,4'-bipyridine]. Single-crystal X-ray diffraction demonstrates that complex 1 represents the uranyl-organic polycatenated framework derived from a simple two-dimensional honeycomb grid network structure via a H 2 NDC linker. Complexes 2-4 contain the dinuclear motifs of the two UO 7 pentagonal and one UO 8 hexagonal bipyramids which are linked by NDC 2- anions creating a (UO 2 ) 4 (NDC) 2 unit, and further extend to a 2D layer through NDC 2- anions. Complex 5 displays a 1D zigzag double chain structure, in which the carboxylate groups of the NDC 2- anions adopt a chelate mode and further extends to a 2D framework via hydrogen bonds. The 1D structure of complex 6 is similar to the zigzag chain of complex 5. In addition, powder X-ray diffraction, elemental analysis, IR, thermal stability and luminescence properties of all complexes have also been investigated in this paper. The photocatalytic properties of the six complexes for the degradation of tetracycline hydrochloride (TC) under UV irradiation have been examined. Moreover, density functional theory (DFT) calculations were carried out to explore the electronic structural and bonding properties of the uranyl complexes 1-6.
Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L.; Yao, Xuebiao
2015-01-01
The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C–MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression. PMID:26240331
Dou, Zhen; Liu, Xing; Wang, Wenwen; Zhu, Tongge; Wang, Xinghui; Xu, Leilei; Abrieu, Ariane; Fu, Chuanhai; Hill, Donald L; Yao, Xuebiao
2015-08-18
The spindle assembly checkpoint (SAC) is a conserved signaling pathway that monitors faithful chromosome segregation during mitosis. As a core component of SAC, the evolutionarily conserved kinase monopolar spindle 1 (Mps1) has been implicated in regulating chromosome alignment, but the underlying molecular mechanism remains unclear. Our molecular delineation of Mps1 activity in SAC led to discovery of a previously unidentified structural determinant underlying Mps1 function at the kinetochores. Here, we show that Mps1 contains an internal region for kinetochore localization (IRK) adjacent to the tetratricopeptide repeat domain. Importantly, the IRK region determines the kinetochore localization of inactive Mps1, and an accumulation of inactive Mps1 perturbs accurate chromosome alignment and mitotic progression. Mechanistically, the IRK region binds to the nuclear division cycle 80 complex (Ndc80C), and accumulation of inactive Mps1 at the kinetochores prevents a dynamic interaction between Ndc80C and spindle microtubules (MTs), resulting in an aberrant kinetochore attachment. Thus, our results present a previously undefined mechanism by which Mps1 functions in chromosome alignment by orchestrating Ndc80C-MT interactions and highlight the importance of the precise spatiotemporal regulation of Mps1 kinase activity and kinetochore localization in accurate mitotic progression.
76 FR 10757 - Combined Mailings of Standard Mail and Periodicals Flats
Federal Register 2010, 2011, 2012, 2013, 2014
2011-02-28
... (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared according to 707.19.0 and these additional... to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC pallets... according to the standards in 8.0 and in the sequence listed below. Merged 5-digit scheme through NDC...
Wang, Jie; Wu, Zexing; Han, Lili; ...
2017-03-07
Here, we develop a simple one-pot synthetic strategy for the general preparation of nitrogen doped carbon supported metal/metal oxides (Co@CoO/NDC, Ni@NiO/NDC and MnO/NDC) derived from the complexing function of (ethylenediamine)tetraacetic acid (EDTA). EDTA serves not only as a resource to tune the morphology in terms of the complexation constant for M–EDTA, but also as a nitrogen and oxygen source for nitrogen doping and metal oxide formation, respectively. When the materials are used as electrocatalysts for the oxygen electrode reaction, Co@CoO/NDC-700 and MnO/NDC-700 show superior electrocatalytic activity towards the oxygen reduction reaction (ORR), while Co@CoO/NDC-700 and Ni@NiO/NDC-700 exhibit excellent oxygen evolutionmore » reaction (OER) activities. Taken together, the resultant Co@CoO/NDC-700 exhibits the best catalytic activity with favorable reaction kinetics and durability as a bi-functional catalyst for the ORR and OER, which is much better than the other two catalysts, Pt/C and Ir/C. Moreover, as an air electrode for a homemade zinc–air battery, Co@CoO/NDC-700 shows superior cell performance with a highest power density of 192.1 mW cm -2, the lowest charge–discharge overpotential and high charge–discharge durability over 100 h.« less
NASA Astrophysics Data System (ADS)
Dong, Jun-Liang; He, Kun-Huan; Wang, Duo-Zhi; Zhang, Ying-Hui; Wang, Dan-Hong
2018-07-01
Three new Co(II) coordination polymers with formulas of {[Co2(L1)(1,4-NDC)2]·3H2O}n (1), [Co3(L2)2(HCOO)2(1,4-NDC)2]n (2) and [Co2(L2)(μ3-OH)(1,4-NDC)1.5]n (3) (1,4-H2NDC = Naphthalene-1,4-dicarboxylic acid, L1 = di(1H-imidazol-1-yl)methane, L2 = 1,4-di(1H-imidazol-1-yl)benzene) were solvothermal synthesized from 1,4-H2NDC with the aid of three different length-controllable auxiliary ligands and fully characterized. Their structures are determined by single-crystal X-ray diffraction, IR spectra, elemental analysis, powder X-ray diffraction and thermogravimetric analysis. Complexes 1 and 3 display 3D framework structures, corresponding to a 6-connected (412·63) net, a 8-connected (424·5·63) net, respectively. However, it is noteworthy that the complex 1 displays a 2-fold interpenetrating framework structure, complex 3 possesses a self-interpenetrating framework structure. Complex 2 displays 2D 4-connected undulating plane net structure. Moreover, magnetic studies indicate antiferromagnetic interactions between the Co(II) ions in the four complexes.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kind, Barbara, E-mail: barbara.kind@uniklinikum-dresden.de; Koehler, Katrin, E-mail: katrin.koehler@uniklinikum-dresden.de; Lorenz, Mike, E-mail: mlorenz@mpi-cbg.de
2009-12-11
The nuclear pore complex (NPC) consists of {approx}30 different proteins and provides the only sites for macromolecular transport between cytoplasm and nucleus. ALADIN was discovered as a new member of the NPC. Mutations in ALADIN are known to cause triple A syndrome, a rare autosomal recessive disorder characterized by adrenal insufficiency, alacrima, and achalasia. The function and exact location of the nucleoporin ALADIN within the NPC multiprotein complex is still unclear. Using a siRNA-based approach we downregulated the three known membrane integrated nucleoporins NDC1, GP210, and POM121 in stably expressing GFP-ALADIN HeLa cells. We identified NDC1 but not GP210 andmore » POM121 as the main anchor of ALADIN within the NPC. Solely the depletion of NDC1 caused mislocalization of ALADIN. Vice versa, the depletion of ALADIN led also to disappearance of NDC1 at the NPC. However, the downregulation of two further membrane-integral nucleoporins GP210 and POM121 had no effect on ALADIN localization. Furthermore, we could show a direct association of NDC1 and ALADIN in NPCs by fluorescence resonance energy transfer (FRET) measurements. Based on our findings we conclude that ALADIN is anchored in the nuclear envelope via NDC1 and that this interaction gets lost, if ALADIN is mutated. The loss of integration of ALADIN in the NPC is a main pathogenetic aspect for the development of the triple A syndrome and suggests that the interaction between ALADIN and NDC1 may be involved in the pathogenesis of the disease.« less
The human Nup107–160 nuclear pore subcomplex contributes to proper kinetochore functions
Zuccolo, Michela; Alves, Annabelle; Galy, Vincent; Bolhy, Stéphanie; Formstecher, Etienne; Racine, Victor; Sibarita, Jean-Baptiste; Fukagawa, Tatsuo; Shiekhattar, Ramin; Yen, Tim; Doye, Valérie
2007-01-01
We previously demonstrated that a fraction of the human Nup107–160 nuclear pore subcomplex is recruited to kinetochores at the onset of mitosis. However, the molecular determinants for its kinetochore targeting and the functional significance of this localization were not investigated. Here, we show that the Nup107–160 complex interacts with CENP-F, but that CENP-F only moderately contributes to its targeting to kinetochores. In addition, we show that the recruitment of the Nup107–160 complex to kinetochores mainly depends on the Ndc80 complex. We further demonstrate that efficient depletion of the Nup107–160 complex from kinetochores, achieved either by combining siRNAs targeting several of its subunits excluding Seh1, or by depleting Seh1 alone, induces a mitotic delay. Further analysis of Seh1-depleted cells revealed impaired chromosome congression, reduced kinetochore tension and kinetochore–microtubule attachment defects. Finally, we show that the presence of the Nup107–160 complex at kinetochores is required for the recruitment of Crm1 and RanGAP1–RanBP2 to these structures. Together, our data thus provide the first molecular clues underlying the function of the human Nup107–160 complex at kinetochores. PMID:17363900
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lin, Hong-Yan; Lu, Huizhe; Le, Mao
2015-03-15
Three new cobalt(II) coordination polymers [Co{sub 2}(1,4-NDC){sub 2}(3-bpye)(H{sub 2}O)] (1), [Co(1,4-NDC)(3-bpfp)(H{sub 2}O)] (2) and [Co(1,4-NDC)(3-bpcb)] (3) [3-bpye=N,N′-bis(3-pyridinecarboxamide)-1,2-ethane, 3-bpfp=bis(3-pyridylformyl)piperazine, 3-bpcb=N,N′-bis(3-pyridinecarboxamide)-1,4-benzene, and 1,4-H{sub 2}NDC=1,4-naphthalenedicarboxylic acid] have been hydrothermally synthesized. The structures of complexes 1–3 have been determined by X-ray single crystal diffraction analyses and further characterized by infrared spectroscopy (IR), powder X-ray diffraction (PXRD) and thermogravimetric analyses (TGA). Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology constructed from 3D [Co{sub 2}(1,4-NDC){sub 2}(H{sub 2}O)]{sub n} framework and bidentate 3-bpye ligands. Complex 2 shows 1D “cage+cage”-like chain formed by 1D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} ribbon chains and [Co{sub 2}(3-bpfp){submore » 2}] loops, which are further linked by hydrogen bonding interactions to form a 3D supramolecular network. Complex 3 displays a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology based on 2D [Co{sub 2}(1,4-NDC){sub 2}]{sub n} layers and bidentate 3-bpcb bridging ligands. The influences of different bis-pyridyl-bis-amide ligands with various spacers on the structures of title complexes are studied. Moreover, the fluorescent properties, electrochemical behaviors and magnetic properties of complexes 1–3 have been investigated. - Graphical abstract: Three multifunctional cobalt(II) complexes constructed from three bis-pyridyl-bis-amide and 1,4-naphthalenedicarboxylic acid have been hydrothermally synthesized and characterized. The fluorescent, electrochemical and magnetic properties of 1–3 have been investigated. - Highlights: • Three multifunctional cobalt(II) complexes based on various bis-pyridyl-bis-amide ligands. • Complex 1 is a 3D coordination structure with 8-connected (4{sup 20}.6{sup 8}) topology. • Complex 2 is a 1D “cage+cage”-like chain. • Complex 3 is a 3D coordination network with a 6-connected (4{sup 12}.6{sup 3}) topology. • The fluorescent, electrochemical and magnetic properties of 1–3 were reported.« less
NASA Astrophysics Data System (ADS)
Xing, Yubo; Liu, Yuqi; Xue, Xiaofei; Wang, Xinying; Li, Wei
2018-02-01
Three new metal-organic coordination polymers, {[Mn2(1,4-NDC)2 (C2H5OH) (DMF) (H2O)]·CH3OH}n(1), {[Mn(III)(1,4-NDC)(C2H5O)][Mn(II)(1,4-NDC)(DMF)(H2O)]}n(2) and {[Cu2(C13H9O4)4(H2O)2]}n(3) based on1,4-H2NDC and its derivative were hydrothermally synthesized (1,4-H2NDC = 1,4-naphthalene-dicarboxylic acid, C13H10O4 = 4-methyl formate-1-naphthalenecarboxylic acid), and characterized by techniques of single crystal X-ray diffraction, infrared spectra (IR), elemental analysis, powder X-ray diffraction(PXRD) and variable-temperature magnetic susceptibility measurements. X-ray crystal structure analyses reveal that complexes 1 and 2 show a same 3,5-connected fsc 3D topology network with the Schlȁfli symbol of {4·6·8}{4·66·83}. But, the valence of some Mn atom in complex 2 take place transition from the +II oxidation state to the +III oxidation state, which may be the effect of the different solvent ratio. In complex 3, the Cu⋯Cu distance of 2.620(13) Å is significantly shorter than the sum of the van der Waals radii of Cu (1.40 Å), resulting in a strong ferromagnetic interaction between the Cu(II) centers. Furthermore, the temperature-dependent magnetic susceptibility measurements exhibit overall antiferromagnetic interactions between manganese ions for complexes 1 and 2, and a strong ferromagnetic interaction between the Cu(II) centers for complex 3.
Shan, Y; Man, C X; Han, X; Li, L; Guo, Y; Deng, Y; Li, T; Zhang, L W; Jiang, Y J
2015-04-01
Most γ-aminobutyric acid (GABA)-producing microorganisms are lactic acid bacteria (LAB), but the yield of GABA is limited in most of these GABA-producing strains. In this study, the production of GABA was carried out by using Lactobacillus plantarum NDC75017, a strain screened from traditional fermented dairy products in China. Concentrations of substrate (l-monosodium glutamate, L-MSG) and coenzyme (pyridoxal-5-phosphate, PLP) of glutamate decarboxylase (GAD) and culture temperature were investigated to evaluate their effects on GABA yield of Lb. plantarum NDC75017. The results indicated that GABA production was related to GAD activity and biomass of Lb. plantarum NDC75017. Response surface methodology was used to optimize conditions of GABA production. The optimal factors for GABA production were L-MSG at 80 mM, PLP at 18 μM, and a culture temperature of 36 °C. Under these conditions, production of GABA was maximized at 314.56 mg/100 g. Addition of Lb. plantarum NDC75017 to a commercial starter culture led to higher GABA production in fermented yogurt. Flavor and texture of the prepared yogurt and the control yogurt did not differ significantly. Thus, Lb. plantarum NDC75017 has good potential for manufacture of GABA-enriched fermented milk products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.
Aurora A kinase contributes to a pole-based error correction pathway
Ye, Anna A.; Deretic, Jovana; Hoel, Christopher M.; Hinman, Albert W.; Cimini, Daniela; Welburn, Julie P.; Maresca, Thomas J.
2015-01-01
Summary Chromosome biorientation, where sister kinetochores attach to microtubules (MTs) from opposing spindle poles, is the configuration that best ensures equal partitioning of the genome during cell division. Erroneous kinetochore-microtubule (kt-MT) attachments are commonplace but often corrected prior to anaphase [1, 2]. Error correction, thought to be mediated primarily by the centromere-enriched Aurora B kinase (ABK) [3-5], typically occurs near spindle poles [6]; albeit, the relevance of this locale is unclear. Furthermore, polar ejection forces (PEFs), highest near poles [7], can stabilize improper attachments by pushing mal-oriented chromosome arms away from spindle poles [8, 9]. Hence, a conundrum: erroneous kt-MT attachments are weakened where PEFs are most likely to strengthen them. Here, we report that Aurora A kinase (AAK) opposes the stabilizing effect of PEFs. AAK activity contributes to phosphorylation of kinetochore substrates near poles and its inhibition results in chromosome mis-alignment and an increased incidence of erroneous kt-MT attachments. Furthermore, AAK directly phosphorylates a site in the N-terminal tail of Ndc80/Hec1 that has been implicated in reducing the affinity of the Ndc80 complex for MTs when phosphorylated [10-12]. We propose that an AAK activity gradient contributes to correcting mal-oriented kt-MT attachments in the vicinity of spindle poles. PMID:26166783
NASA Astrophysics Data System (ADS)
Liu, Guocheng; Chen, Yongqiang; Wang, Xiuli; Chen, Baokuan; Lin, Hongyan
2009-03-01
Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H 2O) 2][Cd(Dpq)(1,8-NDC)]·2H 2O ( 1), [Cd(Dpq)(1,4-NDC)(H 2O)] ( 2), and [Cd(Dpq)(2,6-NDC)] ( 3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H 2NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H 2NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H 2NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and π- π stacking interactions. Compound 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer π- π stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Liu Guocheng; Chen Yongqiang; Wang Xiuli
Three novel Cd(II) coordination polymers, namely, [Cd(Dpq)(1,8-NDC)(H{sub 2}O){sub 2}][Cd(Dpq)(1,8-NDC)].2H{sub 2}O (1), [Cd(Dpq)(1,4-NDC)(H{sub 2}O)] (2), and [Cd(Dpq)(2,6-NDC)] (3) have been obtained from hydrothermal reactions of cadmium(II) nitrate with the mixed ligands dipyrido [3,2-d:2',3'-f]quinoxaline (Dpq) and three structurally related naphthalene-dicarboxylate ligands [1,8-naphthalene-dicarboxylic acid (1,8-H{sub 2}NDC), 1,4-naphthalene-dicarboxylic acid (1,4-H{sub 2}NDC), and 2,6-naphthalene-dicarboxylic acid (2,6-H{sub 2}NDC)]. Single-crystal X-ray diffraction analysis reveals that the three polymers exhibit novel structures due to different naphthalene-dicarboxylic acid. Compound 1 is a novel cocrystal of left- and right-handed helical chains and binuclear complexes and ultimately packed into a 3D supramolecular structure through hydrogen bonds and {pi}-{pi} stacking interactions. Compoundmore » 2 shows a 2D rectangular network (4,4) bridged by 1,4-NDC with two kinds of coordination modes and ultimately packed into a 3D supramolecular structure through inter-layer {pi}-{pi} stacking interactions. Compound 3 is a new 3D coordination polymer with distorted PtS-type network. In addition, the title compounds exhibit blue/green emission in solid state at room temperature. - Graphical abstract: Three novel Cd(II) compounds have been synthesized under hydrothermal conditions exhibiting a systematic variation of architecture by the employment of three structurally related naphthalene-dicarboxylate ligands.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hazari, Debdoot; Jana, Swapan Kumar; Fleck, Michel
2014-11-15
Two lead(II) compounds [Pb{sub 3}(idiac){sub 3}(phen){sub 2}(H{sub 2}O)]·2(H{sub 2}O) (1) and [Pb(ndc)]{sub n} (2), where H{sub 2}idiac=iminodiacetic acid, phen=1,10-phenanthroline and H{sub 2}ndc=naphthalene-2,6-dicarboxylic acid, have been synthesized and structurally characterized. Single crystal X-ray diffraction analysis showed that compound 1 is a discrete trinuclear complex (of two-fold symmetry) which evolves to a supramolecular 3D network via π–π interactions, while in compound 2 the naphthalene dicarboxylate anion act as a linker to form a three dimensional architecture, where the anion adopts a bis-(bidentate bridging) coordination mode connecting four Pb(II) centers. The photoluminescence property of the two complexes has been studied. - graphical abstract:more » Two new topologically different 1D coordination polymers formed by Pb{sub 4} clusters have been synthesized and characterized by x-ray analysis. The luminescence and thermal properties have been studied. - Highlights: • 1 is a trinuclear complex of Pb(II) growing to 3D network via weak interactions. • In 1, layers of (4,4) rhomboidal topology are identified. • In 2, the ndc anion adopts interesting bis-(bidentate bridging) coordination. • In 2, network is reinforced by C–H…π-ring interactions between the ndc rings.« less
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Notification of registrant; blood product... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product Establishments § 607.35 Notification of registrant; blood product establishment registration number and NDC...
CORE IT Services: The NDC and NSSC
NASA Technical Reports Server (NTRS)
Dischinger, Portia
2005-01-01
Contents include the folowing: Virtual NASA Data Center (NDC) overview. NDC challenges. NDC present and future. NDC environment.NDC decomposition NDC opportunities. NDC solution: Horizontally and vertically scalable. Adaptable to new business/mission areas. Competitive-cost and quality. Superior service delivery.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Notification of registrant; blood product establishment registration number and NDC Labeler Code. 607.35 Section 607.35 Food and Drugs FOOD AND DRUG... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product...
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Notification of registrant; blood product establishment registration number and NDC Labeler Code. 607.35 Section 607.35 Food and Drugs FOOD AND DRUG... PRODUCT LISTING FOR MANUFACTURERS OF HUMAN BLOOD AND BLOOD PRODUCTS Procedures for Domestic Blood Product...
Casey, Amanda K.; Dawson, T. Renee; Chen, Jingjing; Friederichs, Jennifer M.; Jaspersen, Sue L.; Wente, Susan R.
2012-01-01
The nuclear envelope in Saccharomyces cerevisiae harbors two essential macromolecular protein assemblies: the nuclear pore complexes (NPCs) that enable nucleocytoplasmic transport, and the spindle pole bodies (SPBs) that mediate chromosome segregation. Previously, based on metazoan and budding yeast studies, we reported that reticulons and Yop1/DP1 play a role in the early steps of de novo NPC assembly. Here, we examined if Rtn1 and Yop1 are required for SPB function in S. cerevisiae. Electron microscopy of rtn1Δ yop1Δ cells revealed lobular abnormalities in SPB structure. Using an assay that monitors lateral expansion of the SPB central layer, we found that rtn1Δ yop1Δ SPBs had decreased connections to the NE compared to wild type, suggesting that SPBs are less stable in the NE. Furthermore, large budded rtn1Δ yop1Δ cells exhibited a high incidence of short mitotic spindles, which were frequently misoriented with respect to the mother–daughter axis. This correlated with cytoplasmic microtubule defects. We found that overexpression of the SPB insertion factors NDC1, MPS2, or BBP1 rescued the SPB defects observed in rtn1Δ yop1Δ cells. However, only overexpression of NDC1, which is also required for NPC biogenesis, rescued both the SPB and NPC associated defects. Rtn1 and Yop1 also physically interacted with Ndc1 and other NPC membrane proteins. We propose that NPC and SPB biogenesis are altered in cells lacking Rtn1 and Yop1 due to competition between these complexes for Ndc1, an essential common component of both NPCs and SPBs. PMID:22798490
National data centre preparedness exercise 2015 (NPE2015): MY-NDC progress result and experience
NASA Astrophysics Data System (ADS)
Rashid, Faisal Izwan Abdul; Zolkaffly, Muhammed Zulfakar
2017-01-01
Malaysia has established the National Data Centre (MY-NDC) in December 2005. MY-NDC is tasked to perform the Comprehensive Nuclear-Test-Ban-Treaty (CTBT) data management as well as providing relevant information for Treaty related events to the Malaysian Nuclear Agency (Nuclear Malaysia) as the CTBT National Authority. In the late 2015, MY-NDC has participated in the National Data Centre Preparedness Exercise 2015 (NPE 2015) which aims to access the level of readiness at MY-NDC. This paper aims at presenting the progress result of NPE 2015 as well as highlighting MY-NDC experience in NPE 2015 compared to previous participation in NPE 2013. MY-NDC has utilised available resources for NPE 2015. In NPE 2015, MY-NDC has performed five type of analyses compared with only two analyses in NPE 2013. Participation in the NPE 2015 has enabled MY-NDC to assess its capability and identify rooms for improvement.
Liu, Yanwei; Hu, Huimin; Zhang, Chuanbao; Wang, Haoyuan; Zhang, Wenlong; Wang, Zheng; Li, Mingyang; Zhang, Wei; Zhou, Dabiao; Jiang, Tao
2015-01-01
The clinical prognosis of patients with glioma is determined by tumor grades, but tumors of different subtypes with equal malignancy grade usually have different prognosis that is largely determined by genetic abnormalities. Oligodendrogliomas (ODs) are the second most common type of gliomas. In this study, integrative analyses found that distribution of TCGA transcriptomic subtypes was associated with grade progression in ODs. To identify critical gene(s) associated with tumor grades and TCGA subtypes, we analyzed 34 normal brain tissue (NBT), 146 WHO grade II and 130 grade III ODs by microarray and RNA sequencing, and identified a co-expression network of six genes (AURKA, NDC80,CENPK, KIAA0101, TIMELESS and MELK) that was associated with tumor grades and TCGA subtypes as well as Ki-67 expression. Validation of the six genes was performed by qPCR in additional 28 ODs. Importantly, these genes also were validated in four high-grade recurrent gliomas and the initial lower-grade gliomas resected from the same patients. Finally, the RNA data on two genes with the highest discrimination potential (AURKA and NDC80) and Ki-67 were validated on an independent cohort (5 NBTs and 86 ODs) by immunohistochemistry. Knockdown of AURKA and NDC80 by siRNAs suppressed Ki-67 expression and proliferation of gliomas cells. Survival analysis showed that high expression of the six genes corporately indicated a poor survival outcome. Correlation and protein interaction analysis provided further evidence for this co-expression network. These data suggest that the co-expression of the six mitosis-regulating genes was associated with malignant progression and prognosis in ODs. PMID:26468983
Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J Ramón; Chiesa, Jean; Gandarillas, Alberto
2010-12-20
How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation.
Zanet, Jennifer; Freije, Ana; Ruiz, María; Coulon, Vincent; Sanz, J. Ramón; Chiesa, Jean; Gandarillas, Alberto
2010-01-01
How human self-renewal tissues co-ordinate proliferation with differentiation is unclear. Human epidermis undergoes continuous cell growth and differentiation and is permanently exposed to mutagenic hazard. Keratinocytes are thought to arrest cell growth and cell cycle prior to terminal differentiation. However, a growing body of evidence does not satisfy this model. For instance, it does not explain how skin maintains tissue structure in hyperproliferative benign lesions. We have developed and applied novel cell cycle techniques to human skin in situ and determined the dynamics of key cell cycle regulators of DNA replication or mitosis, such as cyclins E, A and B, or members of the anaphase promoting complex pathway: cdc14A, Ndc80/Hec1 and Aurora kinase B. The results show that actively cycling keratinocytes initiate terminal differentiation, arrest in mitosis, continue DNA replication in a special G2/M state, and become polyploid by mitotic slippage. They unambiguously demonstrate that cell cycle progression coexists with terminal differentiation, thus explaining how differentiating cells increase in size. Epidermal differentiating cells arrest in mitosis and a genotoxic-induced mitosis block rapidly pushes epidermal basal cells into differentiation and polyploidy. These observations unravel a novel mitosis-differentiation link that provides new insight into skin homeostasis and cancer. It might constitute a self-defence mechanism against oncogenic alterations such as Myc deregulation. PMID:21187932
Nitrogen doped microporous carbon by ZnCl2 activation of protein
NASA Astrophysics Data System (ADS)
Wilson, Praveen; Vijayan, Sujith; Prabhakaran, K.
2017-09-01
ZnCl2 activation of protein containing biomass has been studied for the preparation of N-doped activated carbon (NDC) using powdered dry fish as a source of protein. Nearly 52% increase in the yield of NDC is observed by activation with ZnCl2 due to an increase in the thermal stability of Zn2+-fish protein complex compared to the protein alone. The NDCs obtained are characterized by XRD, IR, XPS, Raman spectroscopy, SEM, TEM, elemental analysis and N2 adsorption-desorption studies. The activation at 550 °C produces NDC with the highest surface area and total pore volume of 1001 m2 g-1 and 0.719 cm3 g-1, respectively, at a ZnCl2 to fish powder weight ratio of 3. A maximum micropore volume of 0.273 cm3 g-1 is obtained at a ZnCl2 to fish powder weight ratio of 1:1. The N-content (12.4-5.2 wt%) decreases with an increase in activation temperature and ZnCl2 to fish powder weight ratio. The NDC obtained by activation at 550 °C at a ZnCl2 to fish powder weight ratio of 1:1 shows the maximum CO2 adsorption capacity of 2.4 and 3.73 mmol g-1 at 25 and 0 °C, respectively, at 1 atmosphere. The CO2 adsorption on the NDC shows excellent cyclic stability and high selectivity over nitrogen gas.
NASA Astrophysics Data System (ADS)
Hao, Hong-Jun; Du, Ming-Yue; Wang, Dan-Feng; Sun, Cheng-Jie; Wang, Zhan-Hui; Huang, Rong-Bin; Zheng, Lan-Sun
2013-09-01
Four Zn(II) coordination complexes, namely {[Zn(pmbm)2(tpa)]·H2O}n (1), {[Zn(pmbm)(phda)]·2(H2O)}n (2), [Zn(pmbm)(aze)]n (3), {[Zn(pmbm)(1,4-ndc)]·2(CH3OH)}n (4) [pmbm = 1-(4-pyridylmethyl)-benzimidazole, H2tpa = terephthalic acid, H2phda = phenylenediacetic acid, H2aze = azelaic acid, 1,4-ndcH2 = 1,4-naphthalenedicarboxylic acid] have been synthesized by solution phase ultrasonic reactions of Zn(AC)2·2H2O with pmbm and various dicarboxylates ligands under the ammoniacal condition. All the complexes have been characterized by elemental analyses, IR spectra and X-ray diffraction. Complexes 1 and 2 exhibit one-dimensional chains structure and complex 3 and 4 are two-dimensional sheets structure with (4,4) topology. Complexes 1-4 spanning from one-dimensional chains to two-dimensional sheets suggest that dicarboxylates play significant roles in the formation of such coordination architectures. The photoluminescences of the complexes were also investigated in the solid state at room temperature.
36 CFR 1260.30 - What is the NDC?
Code of Federal Regulations, 2012 CFR
2012-07-01
... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false What is the NDC? 1260.30 Section 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION...) § 1260.30 What is the NDC? The National Declassification Center (NDC) is established within NARA to...
Negative Differential Conductance in Polyporphyrin Oligomers with Nonlinear Backbones.
Kuang, Guowen; Chen, Shi Zhang; Yan, Linghao; Chen, Ke Qiu; Shang, Xuesong; Liu, Pei Nian; Lin, Nian
2018-01-17
We study negative differential conductance (NDC) effects in polyporphyrin oligomers with nonlinear backbones. Using a low-temperature scanning tunneling microscope, we selectively controlled the charge transport path in single oligomer wires. We observed robust NDC when charge passed through a T-shape junction, bistable NDC when charge passed through a 90° kink and no NDC when charge passed through a 120° kink. Aided by density functional theory with nonequilibrium Green's functions simulations, we attributed this backbone-dependent NDC to bias-modulated hybridization of the electrode states with the resonant transport molecular orbital. We argue this mechanism is generic in molecular systems, which opens a new route of designing molecular NDC devices.
36 CFR § 1260.38 - How does the NDC ensure the quality of declassification reviews?
Code of Federal Regulations, 2013 CFR
2013-07-01
... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true How does the NDC ensure the quality of declassification reviews? § 1260.38 Section § 1260.38 Parks, Forests, and Public Property... INFORMATION The National Declassification Center (NDC) § 1260.38 How does the NDC ensure the quality of...
NASA Technical Reports Server (NTRS)
Effinger, M.; Ellingson, B.; Spohnholtz, T.; Koenig, J.
2001-01-01
An idea is put forth for a nondestructive characterization (NDC) generated algorithm-N curve to replace a S-N curve. A scenario for NDC life determination has been proposed. There are many challenges for the NDC life determination and prediction, but it could yield a grand payoff. The justification for NDC life determination and prediction is documented.
NASA Astrophysics Data System (ADS)
Li, Si-Yu; Liu, Haiwen; Qiao, Jia-Bin; Jiang, Hua; He, Lin
2018-03-01
Negative differential conductance (NDC), characterized by the decreasing current with increasing voltage, has attracted continuous attention for its various novel applications. The NDC typically exists in a certain range of bias voltages for a selected system and controlling the regions of NDC in curves of current versus voltage (I -V ) is experimentally challenging. Here, we demonstrate a magnetic-field-controlled NDC in scanning tunneling spectroscopy of graphene npn junction resonators. The magnetic field not only can switch on and off the NDC, but also can continuously tune the regions of the NDC in the I -V curves. In the graphene npn junction resonators, magnetic fields generate sharp and pronounced Landau-level peaks with the help of the Klein tunneling of massless Dirac fermions. A tip of scanning tunneling microscope induces a relatively shift of the Landau levels in graphene beneath the tip. Tunneling between the misaligned Landau levels results in the magnetic-field-controlled NDC.
Analysis of National Drug Code Identifiers in Ambulatory E-Prescribing.
Dhavle, Ajit A; Ward-Charlerie, Stacy; Rupp, Michael T; Amin, Vishal P; Ruiz, Joshua
2015-11-01
Communication of an accurate and interpretable drug identifier between prescriber and pharmacist is critically important for realizing the potential benefits of electronic prescribing (e-prescribing) while minimizing its risk. The National Drug Code (NDC) is the most commonly used codified drug identifier in ambulatory care e-prescribing, but concerns have been raised regarding its use for this purpose. To (a) assess the frequency of NDC identifier transmission in ambulatory e-prescribing; (b) characterize the type of NDC identifier transmitted (representative, repackaged, obsolete, private label, and unit dose); and (c) assess the level of agreement between drug descriptions corresponding to NDC identifiers in electronic prescriptions (e-prescriptions) and the free-text drug descriptions that were entered by prescribers. We analyzed a sample of 49,997 e-prescriptions that were transmitted by ambulatory care prescribers to outlets of a national retail drugstore chain during a single day in April 2014. The First Databank MedKnowledge drug database was used as the primary reference data base to assess the frequency and types of NDC numbers in the e-prescription messages. The FDA's Comprehensive NDC Standard Product Labeling Data Elements File and the National Library of Medicine's RxNorm data file were used as secondary and tertiary references, respectively, to identify NDC numbers that could not be located in the primary reference file. Three experienced reviewers compared the free-text drug description that had been entered by the prescriber with the drug description corresponding to the NDC number from 1 of the 3 reference database files to identify discrepancies. Two licensed pharmacists with residency training and ambulatory care experience served as final adjudicators. A total of 42,602 e-prescriptions contained a value in the NDC field, of which 42,335 (84.71%) were found in 1 of the 3 study reference databases and were thus considered to be valid NDC numbers. A total of 28,172 (67.70%) e-prescriptions in the sample were found to contain a representative NDC number, according to the definition used by the National Council for Prescription Drug Programs (NCPDP). The remaining e-prescriptions consisted of 4 subtypes of unrepresentative NDC numbers. In 41,298 (97.55%) e-prescriptions that contained an NDC number, the drug description associated with the number from 1 of the 3 data source files pointed to the identical semantic drug concept as the free-text drug description that had been entered by the prescriber. However, in 87 (0.21%) e-prescriptions, the free-text drug descriptions and the drug description associated with the NDC number pointed to completely different semantic drug concepts. We found the use of NDC identifiers in our sample of e-prescriptions to be relatively high. However, approximately one-third consisted of unrepresentative NDC numbers (obsolete, repackaged, unit dose, or private label) that have the potential to create workflow disruptions at the dispensing pharmacy. Most disturbing was our finding that more than 2 out of every 1,000 e-prescriptions in our sample contained a free-text drug description that pointed to a completely different drug concept than that associated with its NDC value. Our study suggests the need for e-prescribing technology vendors to maintain accurate and up-to-date drug database files within their systems and to conduct regular validation checks to ensure that the drug descriptions associated with the NDC identifier and the free-text drug description that is sent in the e-prescription message point to the same drug concept. The FDA may need to consider a more active role in ensuring the accuracy of NDC assignment by drug manufacturers.
Li, Zhi; Zhu, Yizhou; Zhai, Yujia; R Castroagudin, Michelle; Bao, Yifei; White, Tommy E; Glavy, Joseph S
2013-12-01
From the surrounding shell to the inner machinery, nuclear proteins provide the functional plasticity of the nucleus. This study highlights the nuclear association of Pore membrane (POM) protein NDC1 and Werner protein (WRN), a RecQ helicase responsible for the DNA instability progeria disorder, Werner Syndrome. In our previous publication, we connected the DNA damage sensor Werner's Helicase Interacting Protein (WHIP), a binding partner of WRN, to the NPC. Here, we confirm the association of the WRN/WHIP complex and NDC1. In established WRN/WHIP knockout cell lines, we further demonstrate the interdependence of WRN/WHIP and Nucleoporins (Nups). These changes do not completely abrogate the barrier of the Nuclear Envelope (NE) but do affect the distribution of FG Nups and the RAN gradient, which are necessary for nuclear transport. Evidence from WRN/WHIP knockout cell lines demonstrates changes in the processing and nucleolar localization of lamin B1. The appearance of "RAN holes" void of RAN corresponds to regions within the nucleolus filled with condensed pools of lamin B1. From WRN/WHIP knockout cell line extracts, we found three forms of lamin B1 that correspond to mature holoprotein and two potential post-translationally modified forms of the protein. Upon treatment with topoisomerase inhibitors lamin B1 cleavage occurs only in WRN/WHIP knockout cells. Our data suggest the link of the NDC1 and WRN as one facet of the network between the nuclear periphery and genome stability. Loss of WRN complex leads to multiple alterations at the NPC and the nucleolus. © 2013. Published by Elsevier B.V. All rights reserved.
36 CFR 1260.30 - What is the NDC?
Code of Federal Regulations, 2014 CFR
2014-07-01
... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false What is the NDC? 1260.30 Section 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification Center (NDC...
Karikalan, Natarajan; Karthik, Raj; Chen, Shen-Ming; Chen, Hsi-An
2017-04-05
We reported an electrochemical determination of caffeic acid (CA) based on the nitrogen doped carbon (NDC). The described sensor material was prepared by the flame synthesis method, which gave an excellent platform for the synthesis of carbon nanomaterials with the hetero atom dopant. The synthesized material was confirmed by various physical characterizations and it was further characterized by different electrochemical experiments. The NDC modified glassy carbon electrode (NDC/GCE) shows the superior electrocatalytic performance towards the determination of CA with the wide linear concentration range from 0.01 to 350 μM. It achieves the lowest detection limit of 0.0024 μM and the limit of quantification of 0.004 μM. The NDC/GCE-CA sensor reveals the good selectivity, stability, sensitivity and reproducibility which endorsed that the NDC is promising electrode for the determination of CA. In addition, NDC modified electrode is applied to the determination of CA in red wines and acquired good results.
Negative Differential Conductivity in an Interacting Quantum Gas.
Labouvie, Ralf; Santra, Bodhaditya; Heun, Simon; Wimberger, Sandro; Ott, Herwig
2015-07-31
We report on the observation of negative differential conductivity (NDC) in a quantum transport device for neutral atoms employing a multimode tunneling junction. The system is realized with a Bose-Einstein condensate loaded in a one-dimensional optical lattice with high site occupancy. We induce an initial difference in chemical potential at one site by local atom removal. The ensuing transport dynamics are governed by the interplay between the tunneling coupling, the interaction energy, and intrinsic collisions, which turn the coherent coupling into a hopping process. The resulting current-voltage characteristics exhibit NDC, for which we identify atom number-dependent tunneling as a new microscopic mechanism. Our study opens new ways for the future implementation and control of complex neutral atom quantum circuits.
36 CFR § 1260.30 - What is the NDC?
Code of Federal Regulations, 2013 CFR
2013-07-01
... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true What is the NDC? § 1260.30 Section § 1260.30 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification Center (NDC...
Sec66-Dependent Regulation of Yeast Spindle-Pole Body Duplication Through Pom152
Katta, Santharam S.; Chen, Jingjing; Gardner, Jennifer M.; Friederichs, Jennifer M.; Smith, Sarah E.; Gogol, Madelaine; Unruh, Jay R.; Slaughter, Brian D.; Jaspersen, Sue L.
2015-01-01
In closed mitotic systems such as Saccharomyces cerevisiae, the nuclear envelope (NE) does not break down during mitosis, so microtubule-organizing centers such as the spindle-pole body (SPB) must be inserted into the NE to facilitate bipolar spindle formation and chromosome segregation. The mechanism of SPB insertion has been linked to NE insertion of nuclear pore complexes (NPCs) through a series of genetic and physical interactions between NPCs and SPB components. To identify new genes involved in SPB duplication and NE insertion, we carried out genome-wide screens for suppressors of deletion alleles of SPB components, including Mps3 and Mps2. In addition to the nucleoporins POM152 and POM34, we found that elimination of SEC66/SEC71/KAR7 suppressed lethality of cells lacking MPS2 or MPS3. Sec66 is a nonessential subunit of the Sec63 complex that functions together with the Sec61 complex in import of proteins into the endoplasmic reticulum (ER). Cells lacking Sec66 have reduced levels of Pom152 protein but not Pom34 or Ndc1, a shared component of the NPC and SPB. The fact that Sec66 but not other subunits of the ER translocon bypass deletion mutants in SPB genes suggests a specific role for Sec66 in the control of Pom152 levels. Based on the observation that sec66∆ does not affect the distribution of Ndc1 on the NE or Ndc1 binding to the SPB, we propose that Sec66-mediated regulation of Pom152 plays an NPC-independent role in the control of SPB duplication. PMID:26510791
Wang, Lin; Chen, Xiaoshuang; Hu, Yibin; Yu, Anqi; Lu, Wei
2014-11-07
Recent observations of the negative differential conductance (NDC) phenomenon in graphene field-effect transistors (FET) open up new opportunities for their application in graphene-based fast switches, frequency multipliers and, most importantly, in high frequency oscillators up to the terahertz regime. Unlike conventional two-terminal NDC devices that rely on resonant tunneling and inter-valley transferring, in the present work, it has been shown that the universal NDC phenomenon of graphene-based FETs originates from their intrinsic nonlinear carrier transport under a strong electric field. The operation of graphene-NDC devices depends strongly on the interface between graphene and dielectric materials, the scattering-limited carrier mobility, and on the saturation velocity. To reveal such NDC behavior, the output characteristics of GFET are investigated rigorously, with both an analytical model and self-consistent transport equation, and with a multi-electrical parameter simulation. It is demonstrated that the contact-induced doping effect plays an important role in the operational efficiency of graphene-based NDC devices, rather than the ambipolar behavior associated with the competition between electron and hole conductances. In the absence of a NDC regime or beyond one, ambipolar transport starts at Vds > 2Vgs at the drain end, and as the dielectric layer begins to thin down, the kink-like saturation output characteristic is enhanced by the quantum capacitance contribution. These observations reveal the intrinsic mechanism of the NDC effect and open up new opportunities for the performance improvement of GFETs in future high-frequency applications, beyond the current paradigm based on two-terminal diodes.
US NDC Modernization Iteration E1 Prototyping Report: User Interface Framework
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lober, Randall R.
2014-12-01
During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the User Interface Framework (UIF) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.
US NDC Modernization Iteration E1 Prototyping Report: Common Object Interface
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lewis, Jennifer E.; Hess, Michael M.
2014-12-01
During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team completed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the Common Object Interface (COI) in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.
US NDC Modernization Iteration E1 Prototyping Report: Processing Control Framework
DOE Office of Scientific and Technical Information (OSTI.GOV)
Prescott, Ryan; Hamlet, Benjamin R.
2014-12-01
During the first iteration of the US NDC Modernization Elaboration phase (E1), the SNL US NDC modernization project team developed an initial survey of applicable COTS solutions, and established exploratory prototyping related to the processing control framework in support of system architecture definition. This report summarizes these activities and discusses planned follow-on work.
Walthery, Pierre; Stafford, Mai; Nazroo, James; Whitehead, Margaret; Dibben, Christopher; Halliday, Emma; Povall, Sue; Popay, Jennie
2015-01-01
Background A large body of evidence documents the adverse relationship between concentrated deprivation and health. Among the evaluations of regeneration initiatives to tackle these spatial inequalities, few have traced the trajectories of individuals over time and fewer still have employed counterfactual comparison. We investigate the impact of one such initiative in England, the New Deal for Communities (NDC), which ran from 1999 to 2011, on socioeconomic inequalities in health trajectories. Methods Latent Growth Curve modelling of within-person changes in self-rated health, mental health and life satisfaction between 2002 and 2008 of an analytical cohort of residents of 39 disadvantaged areas of England in which the NDC was implemented, compared with residents of comparator, non-intervention areas, focusing on: (1) whether differences over time in outcomes can be detected between NDC and comparator areas and (2) whether interventions may have altered socioeconomic differences in outcomes. Results No evidence was found for an overall improvement in the three outcomes, or for significant differences in changes in health between respondents in NDC versus comparator areas. However, we found a weakly significant gap in life satisfaction and mental health between high and low socioeconomic status individuals in comparator areas which widened over time to a greater extent than in NDC areas. Change over time in the three outcomes was non-linear: individual improvements among NDC residents were largest before 2006. Conclusions There is limited evidence that the NDC moderated the impact of socioeconomic factors on mental health and life satisfaction trajectories. Furthermore, any NDC impact was strongest in the first 6 years of the programmes. PMID:26085649
Walthery, Pierre; Stafford, Mai; Nazroo, James; Whitehead, Margaret; Dibben, Christopher; Halliday, Emma; Povall, Sue; Popay, Jennie
2015-08-01
A large body of evidence documents the adverse relationship between concentrated deprivation and health. Among the evaluations of regeneration initiatives to tackle these spatial inequalities, few have traced the trajectories of individuals over time and fewer still have employed counterfactual comparison. We investigate the impact of one such initiative in England, the New Deal for Communities (NDC), which ran from 1999 to 2011, on socioeconomic inequalities in health trajectories. Latent Growth Curve modelling of within-person changes in self-rated health, mental health and life satisfaction between 2002 and 2008 of an analytical cohort of residents of 39 disadvantaged areas of England in which the NDC was implemented, compared with residents of comparator, non-intervention areas, focusing on: (1) whether differences over time in outcomes can be detected between NDC and comparator areas and (2) whether interventions may have altered socioeconomic differences in outcomes. No evidence was found for an overall improvement in the three outcomes, or for significant differences in changes in health between respondents in NDC versus comparator areas. However, we found a weakly significant gap in life satisfaction and mental health between high and low socioeconomic status individuals in comparator areas which widened over time to a greater extent than in NDC areas. Change over time in the three outcomes was non-linear: individual improvements among NDC residents were largest before 2006. There is limited evidence that the NDC moderated the impact of socioeconomic factors on mental health and life satisfaction trajectories. Furthermore, any NDC impact was strongest in the first 6 years of the programmes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
NASA Astrophysics Data System (ADS)
Xia, Tifeng; Zhu, Fengliang; Cui, Yuanjing; Yang, Yu; Wang, Zhiyu; Qian, Guodong
2017-01-01
A water-stable metal-organic framework (MOF) EuNDC has been synthesized for selective detection of the well-known contaminant and toxicant picric acid (PA) in aqueous solution. Due to the photo-induced electron transfer and self-absorption mechanism, EuNDC displayed rapid, selective and sensitive detection of PA with a detection limit of 37.6 ppb. Recyclability experiments revealed that EuNDC retains its initial luminescent intensity and same quenching efficiency in each cycle, suggesting high photostability and reusability for long-term sensing applications. The excellent detection performance of EuNDC makes it a promising PA sensing material for practical applications.
Nishibata, Toyohide; Tashiro, Kouichi; Kanahori, Sumiko; Hashizume, Chieko; Kitagawa, Machiko; Okuma, Kazuhiro; Gordon, Dennis T
2009-09-09
Total nondigestible carbohydrate (NDC) in foods was determined by combining, not modifications, AOAC Official Methods 991.43, 2001.03, and 2002.02. Total NDC included insoluble dietary fiber (IDF) + high-molecular-weight soluble dietary fiber (HMWSDF), nondigestible oligosaccharides (NDO) not precipitated in ethanol solution, and resistant starch (RS). Eight sources of NDC (cellulose, wheat bran, gum arabic, resistant maltodextrin, polydextrose, fructooligosaccharide, galactooligosaccharides, and RS) were incorporated in different combinations into standard formula bread samples. All of the NDC sources and bread samples were analyzed for their (1) IDF + HMWSDF content with corrections for residual RS amount using AOAC Official Method 991.43, (2) NDO by liquid chromatography (LC) in AOAC Official Method 2001.03, and (3) RS by AOAC Official Method 2002.02. The correlation coefficient (R(2)) comparing calculated amounts versus measured amounts of total NDC in 11 bread samples was 0.92. Analysis of commercial food samples was also well matched with the DF + NDO value on their nutritional label. Consequently, we confirmed a single measurement of LC can determine all NDO in foods, and total NDC in foods can be determined by unifying existing AOAC Official Methods.
Electrical Spin-Injection into Silicon and Spin FET
2010-02-18
differential conductance ( NDC ), which saw the limelight with the realization of the Esaki tunneling diode, had been predicted and observed to occur in a...collector current of a tunneling emitter bipolar transistor, i.e., negative differential transconductance NDTC. Gate controlled NDC had been observed in...measurement and simulation results are relevant as well for other NDC geometries such as FET style tunnel transistors since they offer crucial
NASA Astrophysics Data System (ADS)
Bryant, D. L.; Ayers, J. C.; Gao, S.; Miller, C. F.; Zhang, H.
2002-05-01
The Northern Dabie Complex (NDC) has been proposed to be either a Paleozoic magmatic arc, an exhumed piece of subducted continental crust, or young crust produced almost entirely by Cretaceous extensional magmatism. Ion microprobe zircon 238U-206Pb ages of separates from NDC gneisses center around 689Ma (+/- 31(95%CL)), consistent with the characteristic zircon dates of the Yangtze Craton [1]. Field observations also show that these gneisses, ranging from granitic to dioritic composition, make up a sizeable area ( ~30%) of the NDC. Zircon separates from the Baimajian granitoid, the largest of the widespread Cretaceous intrusions in the NDC, have yielded ages clustered around 677Ma (+/- 79), and 120Ma (+/- 3.4), the latter of which agrees with ion probe Th-Pb monazite ages. The ~700Ma age indicates that this intrusion may be linked with partial melting of underlying Yangtze crust, while the 120Ma age is the age of its crystallization. Granitic intrusions from Sanzushi and Yerenshai in the Dabie ultrahigh-pressure (UHP) region also show clusters of ages at 714Ma (+/- 55) from zircon cores, as well as rims around 250Ma (+/- 38), which is interpreted as the time of collision of the two continental blocks. These age data support the hypothesis set forth by Zhang et al. [2] using Sm-Nd and Pb isotopic data, that the Yangtze block lies beneath the exhumed UHP belt and outcrops as the NDC, which lies between the UHP belt and the Sino-Korean/Yangtze suture. The Baimajian granitoid, however, also shows a range of older zircon core ages from 1.4-2.0Ga, which may represent the early stages of formation of the Yangtze craton. Zhang et al. [2] suggested craton formation at 1.6-2.4Ga but few such ages have been reported for rocks of the Yangtze or Sino-Korean cratons. 1. Hacker, et al. (2000) Journal of Geophysical Research. Vol. 105. p. 13,339. 2. Zhang, et al. (In press) Chemical Geology.
Observation of negative differential capacitance (NDC) in Ti Schottky diodes on SiGe islands
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rangel-Kuoppa, Victor-Tapio; Jantsch, Wolfgang; Tonkikh, Alexander
2013-12-04
The Negative Differential Capacitance (NDC) effect on Ti Schottky diodes formed on n-type Silicon samples with embedded Germanium Quantum Dots (QDs) is observed and reported. The NDC-effect is detected using capacitance-voltage (CV) method at temperatures below 200 K. It is explained by the capture of electrons in Germanium QDs. Our measurements reveal that each Ge QD captures in average eight electrons.
Kif4 Is Essential for Mouse Oocyte Meiosis.
Camlin, Nicole J; McLaughlin, Eileen A; Holt, Janet E
2017-01-01
Progression through the meiotic cell cycle must be strictly regulated in oocytes to generate viable embryos and offspring. During mitosis, the kinesin motor protein Kif4 is indispensable for chromosome condensation and separation, midzone formation and cytokinesis. Additionally, the bioactivity of Kif4 is dependent on phosphorylation via Aurora Kinase B and Cdk1, which regulate Kif4 function throughout mitosis. Here, we examine the role of Kif4 in mammalian oocyte meiosis. Kif4 localized in the cytoplasm throughout meiosis I and II, but was also observed to have a dynamic subcellular distribution, associating with both microtubules and kinetochores at different stages of development. Co-localization and proximity ligation assays revealed that the kinetochore proteins, CENP-C and Ndc80, are potential Kif4 interacting proteins. Functional analysis of Kif4 in oocytes via antisense knock-down demonstrated that this protein was not essential for meiosis I completion. However, Kif4 depleted oocytes displayed enlarged polar bodies and abnormal metaphase II spindles, indicating an essential role for this protein for correct asymmetric cell division in meiosis I. Further investigation of the phosphoregulation of meiotic Kif4 revealed that Aurora Kinase and Cdk activity is critical for Kif4 kinetochore localization and interaction with Ndc80 and CENP-C. Finally, Kif4 protein but not gene expression was found to be upregulated with age, suggesting a role for this protein in the decline of oocyte quality with age.
Participation of the NDC Austria at the NDC Preparedness Exercise 2012
NASA Astrophysics Data System (ADS)
Mitterbauer, Ulrike; Wotawa, Gerhard; Schraick, Irene
2013-04-01
NDC Preparedness Exercises (NPEs) are conducted annually by the National Data Centers (NDCs) of CTBT States Signatories to train the detection of a (hypothetical) nuclear test. During the NDC Preparedness Exercise 2012, a fictitious radionuclide scenario originating from a real seismic event (mining explosion) was calculated by the German NDC and distributed among all NDCs. For the scenario computation, it was assumed that the selected seismic event was the epicentre of an underground nuclear fission explosion. The scenario included detections of the Iodine isotopes I-131 and I-133 (both particulates), and the Radioxenon Isotopes Xe-133, Xe-133M, Xe-131M and Xe-135 (noble gas). By means of atmospheric transport modelling (ATM), concentrations of all these six isotopes which would result from the hypothetical explosion were calculated and interpolated to the IMS station locations. The participating NDCs received information about the concentration of the isotopes at the station locations without knowing the underlying seismic event. The aim of the exercise was to identify this event based on the detection scenario. The Austrian NDC performed the following analyses: • Atmospheric backtracking and data fusion to identify seismic candidate events, • Seismic analysis of candidate events within the possible source region, • Atmospheric transport modelling (forward mode) from identified candidate events, comparison between "measured" and simulated concentrations based on certain release assumptions. The main goal of the analysis was to identify the event selected by NDC Germany to calculate the radionuclide scenario, and to exclude other events. In the presentation, the analysis methodology as well as the final results and conclusions will be shown and discussed in detail.
Solar tower enhanced natural draft dry cooling tower
NASA Astrophysics Data System (ADS)
Yang, Huiqiang; Xu, Yan; Acosta-Iborra, Alberto; Santana, Domingo
2017-06-01
Concentrating Solar Power (CSP) plants are located in desert areas where the Direct Normal Irradiance (DNI) value is very high. Since water resource is scarcely available, mechanical draft cooing technology is commonly used, with power consumption of mechanical fans being approximately 2% of the total power generated. Today, there is only one solar power plant (Khi Solar One in South Africa) uses a condenser installed in a Natural Draft Cooling (NDC) tower that avoids the windage loss of water occurring in wet cooling towers. Although, Khi Solar One is a cavity receiver power tower, the receivers can be hung onto the NDC tower. This paper looks at a novel integration of a NDC tower into an external molten salt receiver of a solar power plant, which is one of a largest commercial molten salt tower in China, with 100MWe power capacity. In this configuration study, the NDC tower surrounds the concrete tower of the receiver concentrically. In this way, the receiver concrete tower is the central support of the NDC tower, which consists of cable networks that are fixed to the concrete tower and suspended at a certain height over the floor. The cable networks support the shell of the NDC tower. To perform a preliminary analysis of the behavior of this novel configuration, two cases of numerical simulation in three dimensional (3D) models have been solved using the commercial Computational Fluid Dynamics (CFD) code, ANSYS Fluent 6.3. The results show that the integration of the NDC tower into an external central receiver tower is feasible. Additionally, the total heat transfer rate is not reduced but slightly increases when the molten salt receiver is in operation because of the additional natural draft induced by the high temperature of the receiver.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Xia, Tifeng; Zhu, Fengliang; Cui, Yuanjing, E-mail: cuiyj@zju.edu.cn
A water-stable metal-organic framework (MOF) EuNDC has been synthesized for selective detection of the well-known contaminant and toxicant picric acid (PA) in aqueous solution. Due to the photo-induced electron transfer and self-absorption mechanism, EuNDC displayed rapid, selective and sensitive detection of PA with a detection limit of 37.6 ppb. Recyclability experiments revealed that EuNDC retains its initial luminescent intensity and same quenching efficiency in each cycle, suggesting high photostability and reusability for long-term sensing applications. The excellent detection performance of EuNDC makes it a promising PA sensing material for practical applications. - Graphical abstract: A water-stable europium-based metal-organic framework hasmore » been reported for highly selective sensing of picric acid (PA) with a detection limit of 37.6 ppb in aqueous solution. - Highlights: • A water-stable metal-organic framework (MOF) EuNDC was synthesized. • The highly selective detection of picric acid with a detection limit of 37.6 ppb was realized. • The detection mechanism were also presented and discussed.« less
Modeling of frequency-dependent negative differential capacitance in InGaAs/InP photodiode
NASA Astrophysics Data System (ADS)
Wang, Yidong; Chen, Jun; Xu, Jintong; Li, Xiangyang
2018-03-01
The negative differential capacitance (NDC) of p-i-n InGaAs/InP photodetector has been clearly observed, and the small signal model of frequency-dependent NDC is established, based on the accumulation and emission of electrons at the p-InP/i-InGaAs interface. The NDC phenomenon is contributed by the additional capacitance (CT), which is caused by the charging-discharging process in the p-InP/i-InGaAs interface. It is found that the NDC becomes more obvious with decreasing frequency, which is consistent with the conclusion of the experiment. It is proved that the probability of electron capture/escape in the p-i interface is affected by frequency. Therefore, the smaller frequency applied, the higher additional capacitance is obtained.
Combes, Guillaume; Barysz, Helena; Garand, Chantal; Gama Braga, Luciano; Alharbi, Ibrahim; Thebault, Philippe; Murakami, Luc; Bryne, Dominic P; Stankovic, Stasa; Eyers, Patrick A; Bolanos-Garcia, Victor M; Earnshaw, William C; Maciejowski, John; Jallepalli, Prasad V; Elowe, Sabine
2018-03-19
Monopolar spindle 1 (Mps1) is a conserved apical kinase in the spindle assembly checkpoint (SAC) that ensures accurate segregation of chromosomes during mitosis. Mps1 undergoes extensive auto- and transphosphorylation, but the regulatory and functional consequences of these modifications remain unclear. Recent findings highlight the importance of intermolecular interactions between the N-terminal extension (NTE) of Mps1 and the Hec1 subunit of the NDC80 complex, which control Mps1 localization at kinetochores and activation of the SAC. Whether the NTE regulates other mitotic functions of Mps1 remains unknown. Here, we report that phosphorylation within the NTE contributes to Mps1 activation through relief of catalytic autoinhibition that is mediated by the NTE itself. Moreover, we find that this regulatory NTE function is independent of its role in Mps1 kinetochore recruitment. We demonstrate that the NTE autoinhibitory mechanism impinges most strongly on Mps1-dependent SAC functions and propose that Mps1 activation likely occurs sequentially through dimerization of a "prone-to-autophosphorylate" Mps1 conformer followed by autophosphorylation of the NTE prior to maximal kinase activation segment trans-autophosphorylation. Our observations underline the importance of autoregulated Mps1 activity in generation and maintenance of a robust SAC in human cells. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Engineering negative differential conductance with the Cu(111) surface state.
Heinrich, B W; Rastei, M V; Choi, D-J; Frederiksen, T; Limot, L
2011-12-09
Low-temperature scanning tunneling microscopy and spectroscopy are employed to investigate electron tunneling from a C60-terminated tip into a Cu(111) surface. Tunneling between a C60 orbital and the Shockley surface states of copper is shown to produce negative differential conductance (NDC) contrary to conventional expectations. NDC can be tuned through barrier thickness or C60 orientation up to complete extinction. The orientation dependence of NDC is a result of a symmetry matching between the molecular tip and the surface states.
US NDC Modernization Iteration E2 Prototyping Report: User Interface Framework
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lewis, Jennifer E.; Palmer, Melanie A.; Vickers, James Wallace
2014-12-01
During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on Rich Client Platform (RCP) exploratory prototyping related to the User Interface Framework (UIF). The team also developed a survey of browser-based User Interface solutions and completed exploratory prototyping for selected solutions. This report presents the results of the browser-based UI survey, summarizes the E2 browser-based UI and RCP prototyping work, and outlines a path forward for the third iteration of the Elaboration phase (E3).
Bulgarian National Digital Seismological Network
NASA Astrophysics Data System (ADS)
Dimitrova, L.; Solakov, D.; Nikolova, S.; Stoyanov, S.; Simeonova, S.; Zimakov, L. G.; Khaikin, L.
2011-12-01
The Bulgarian National Digital Seismological Network (BNDSN) consists of a National Data Center (NDC), 13 stations equipped with RefTek High Resolution Broadband Seismic Recorders - model DAS 130-01/3, 1 station equipped with Quanterra 680 and broadband sensors and accelerometers. Real-time data transfer from seismic stations to NDC is realized via Virtual Private Network of the Bulgarian Telecommunication Company. The communication interruptions don't cause any data loss at the NDC. The data are backed up in the field station recorder's 4Mb RAM memory and are retransmitted to the NDC immediately after the communication link is re-established. The recorders are equipped with 2 compact flash disks able to save more than 1 month long data. The data from the flash disks can be downloaded remotely using FTP. The data acquisition and processing hardware redundancy at the NDC is achieved by two clustered SUN servers and two Blade Workstations. To secure the acquisition, processing and data storage processes a three layer local network is designed at the NDC. Real-time data acquisition is performed using REFTEK's full duplex error-correction protocol RTPD. Data from the Quanterra recorder and foreign stations are fed into RTPD in real-time via SeisComP/SeedLink protocol. Using SeisComP/SeedLink software the NDC transfers real-time data to INGV-Roma, NEIC-USA, ORFEUS Data Center. Regional real-time data exchange with Romania, Macedonia, Serbia and Greece is established at the NDC also. Data processing is performed by the Seismic Network Data Processor (SNDP) software package running on the both Servers. SNDP includes subsystems: Real-time subsystem (RTS_SNDP) - for signal detection; evaluation of the signal parameters; phase identification and association; source estimation; Seismic analysis subsystem (SAS_SNDP) - for interactive data processing; Early warning subsystem (EWS_SNDP) - based on the first arrived P-phases. The signal detection process is performed by traditional STA/LTA detection algorithm. The filter parameters of the detectors are defined on the base of previously evaluated ambient noise at the seismic stations. Some extra modules for network command/control, state-of-health network monitoring and data archiving are running as well in the National Data Center. Three types of archives are produced in the NDC - two continuous - miniSEED format and RefTek PASSCAL format; and one event oriented in CSS3.0 scheme format. Modern digital equipment and broad-band seismometers installed at Bulgarian seismic stations, careful selection of the software packages for automatic and interactive data processing in the data center proved to be suitable choice for the purposes of BNDSN and NDC: ? to ensure reliable automatic localization of the seismic events and rapid notification of the governmental authorities in case of felt earthquakes on the territory of Bulgaria; ? to provide a modern basis for seismological studies in Bulgaria.
Low-bias negative differential conductance controlled by electrode separation
NASA Astrophysics Data System (ADS)
Yi, Xiao-Hua; Liu, Ran; Bi, Jun-Jie; Jiao, Yang; Wang, Chuan-Kui; Li, Zong-Liang
2016-12-01
The electronic transport properties of a single thiolated arylethynylene molecule with 9,10-dihydroanthracene core, denoted as TADHA, is studied by using non-equilibrium Green’s function formalism combined with ab initio calculations. The numerical results show that the TADHA molecule exhibits excellent negative differential conductance (NDC) behavior at lower bias regime as probed experimentally. The NDC behavior of TADHA molecule originates from the Stark effect of the applied bias voltage, by which the highest occupied molecular orbital (HOMO) and the HOMO-1 are pulled apart and become localized. The NDC behavior of TADHA molecular system is tunable by changing the electrode distance. Shortening the electrode separation can enhance the NDC effect which is attributed to the possible increase of coupling between the two branches of TADHA molecule. Project supported by the National Natural Science Foundation of China (Grant Nos. 11374195 and 11405098) and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2013FM006).
42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.
Code of Federal Regulations, 2011 CFR
2011-10-01
... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...
42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.
Code of Federal Regulations, 2013 CFR
2013-10-01
... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...
42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.
Code of Federal Regulations, 2012 CFR
2012-10-01
... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...
42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.
Code of Federal Regulations, 2014 CFR
2014-10-01
... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...
42 CFR 447.520 - FFP: Conditions relating to physician-administered drugs.
Code of Federal Regulations, 2010 CFR
2010-10-01
... using Healthcare Common Procedure Coding System codes or NDC numbers in order to secure rebates. (2) As... Medicaid Program using NDC numbers in order to secure rebates. (b) As of January 1, 2007, a State must...
Phosphorylation of human INO80 is involved in DNA damage tolerance
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kato, Dai; Waki, Mayumi; Umezawa, Masaki
Highlights: Black-Right-Pointing-Pointer Depletion of hINO80 significantly reduced PCNA ubiquitination. Black-Right-Pointing-Pointer Depletion of hINO80 significantly reduced nuclear dots intensity of RAD18 after UV irradiation. Black-Right-Pointing-Pointer Western blot analyses showed phosphorylated hINO80 C-terminus. Black-Right-Pointing-Pointer Overexpression of phosphorylation mutant hINO80 reduced PCNA ubiquitination. -- Abstract: Double strand breaks (DSBs) are the most serious type of DNA damage. DSBs can be generated directly by exposure to ionizing radiation or indirectly by replication fork collapse. The DNA damage tolerance pathway, which is conserved from bacteria to humans, prevents this collapse by overcoming replication blockages. The INO80 chromatin remodeling complex plays an important role in themore » DNA damage response. The yeast INO80 complex participates in the DNA damage tolerance pathway. The mechanisms regulating yINO80 complex are not fully understood, but yeast INO80 complex are necessary for efficient proliferating cell nuclear antigen (PCNA) ubiquitination and for recruitment of Rad18 to replication forks. In contrast, the function of the mammalian INO80 complex in DNA damage tolerance is less clear. Here, we show that human INO80 was necessary for PCNA ubiquitination and recruitment of Rad18 to DNA damage sites. Moreover, the C-terminal region of human INO80 was phosphorylated, and overexpression of a phosphorylation-deficient mutant of human INO80 resulted in decreased ubiquitination of PCNA during DNA replication. These results suggest that the human INO80 complex, like the yeast complex, was involved in the DNA damage tolerance pathway and that phosphorylation of human INO80 was involved in the DNA damage tolerance pathway. These findings provide new insights into the DNA damage tolerance pathway in mammalian cells.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Prescott, Ryan; Marger, Bernard L.; Chiu, Ailsa
During the second iteration of the US NDC Modernization Elaboration phase (E2), the SNL US NDC Modernization project team completed follow-on COTS surveys & exploratory prototyping related to the Object Storage & Distribution (OSD) mechanism, and the processing control software infrastructure. This report summarizes the E2 prototyping work.
Nitrogen doped activated carbon from pea skin for high performance supercapacitor
NASA Astrophysics Data System (ADS)
Ahmed, Sultan; Ahmed, Ahsan; Rafat, M.
2018-04-01
In this work, nitrogen doped porous carbon (NDC) has been synthesized employing a facile two-step process. Firstly, carbon precursor (pea skin) was heated with melamine (acting as nitrogen source) followed by activation with KOH in different ratios. The dependence of porosity and nitrogen content on impregnation ratio was extensively studied. Other textural properties of prepared NDC sample were studied using standard techniques of material characterization. The electrochemical performance of NDC sample as an electrode was studied in two-electrode symmetric supercapacitor system. 1 M LiTFSI (lithium bis-trifluoromethanesulfonimide) solution in IL EMITFSI (1-Ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide), was used as electrolyte. It was found that the fabricated supercapacitor cell offers high values of specific capacitance (141.1 F g‑1), specific energy (19.6 Wh kg‑1) and specific power (25.4 kW kg‑1) at current density of 1.3 A g‑1. More importantly, the fabricated supercapacitor cell shows capacitance retention of ∼75%, for more than 5000 cycles. The enhanced performance of NDC sample is primarily due to large surface area with favorable surface structure (contributing to double layer capacitance) and presence of nitrogen functionalities (contributing to pseudo-capacitance). Such important features make the synthesized NDC sample, an attractive choice for electrode material in high performance supercapacitor.
Gutiérrez, M; López-González, M; Sánchez, F; Douhal, A
2017-07-21
Light harvesting is a natural phenomenon that scientists try to mimic in artificial systems. Having this in mind, attention has been focused on using new smart-materials for photonics. Herein, we report on the photobehaviour of a Zr-NDC MOF (NDC = dimethyl 2,6-naphthalenedicarboxylate) and its composite material, Coumarin153@Zr-NDC, embedded within a polymeric membrane of poly[bisphenol A carbonate-co-4,4'-(3,3,5-trimethylcyclohexylidene)diphenol carbonate] (PC). For the mixed matrix membrane (MMM) Zr-NDC/PC, we observed interparticle excimer-like formation, taking place in times shorter than 15 ps and giving rise to a red-shifted broad emission band. The interparticle interactions are supported by the SEM images, as they reflect the contact between the MOF crystals. The C153@Zr-NDC/PC material presents an energy transfer (ET) process from the excited MOF to the trapped C153 molecules in 820 ps, with a 35 nm red-shifted emission band corresponding to C153 in PC. The fluorescence quantum yield, as a result of this ET from the MOF, is high enough (25%) to explore the possibility of using this new composite material in a LED device. To elucidate the observed photobehavior, we compared it with those of C153/PC and (2,6-NDC + C153)/PC films. These results shed light on the spectroscopic and dynamical properties of these new composite materials formed by a highly fluorescent molecule, and easily synthesized MOFs and polymeric matrices, opening the way for more research based on these mixed inorganic and organic compounds for possible applications in the fields of luminescence sensing and emitting devices.
NASA Astrophysics Data System (ADS)
Cui, G. Y.; Wang, C. Y.; Xiang, G. Q.; Zhou, B.
2018-01-01
In this work, a nitrogen doped carbon material (NDC) was prepared by using a copper adenine complex as precursor and applied to electrochemical sensing of Vitamin B2 (VB2). The experimental results show that the nitrogen doped carbon material is obtained after calcination at 650 °C under argon atmosphere, afterwards, which were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), fourier transform infrared (FT-IR), and electrochemical method. According to the XRD data, the product was a carbon material, and infrared data demonstrates that there are two kinds of carbonyl nitrogen combination, respectively, C-N and C = N combination of ways. Importantly, we used NDC to construct electrochemical biosensor to detect VB2 by differential pulse voltammetry (DPV). The linear range was 6 × 10-6 - 3.5 × 10-4 M (R=0.9962), the minimum detection limit was 5.4 × 10-6 M, and the sensitivity is better. Consequently, it has better sensing performance.
The (Nutrition Education) Gospel According to NDC.
ERIC Educational Resources Information Center
Kilburn, Eric
1978-01-01
Discusses the flaws in nutrition education as presented by the National Dairy Council (NDC). Those discussed include the presentation of diets that contain high amounts of sugar and cholesterol and the failure to connect diet to heart disease. Suggests ways of monitoring these materials in the schools. (MA)
Gender and nurturance in families of children with neurodevelopmental conditions.
Shapiro, Danielle N; Dixon-Thomas, Pamela; Warschausky, Seth
2014-05-01
This study tested the hypothesis that gender differences in parent-reported nurturance of children would be attenuated in families of children with neurodevelopmental conditions (NDCs). In this cross-sectional study, participants included 49 (29 male) children diagnosed with an NDC and 60 (30 male) typically developing (TD) children. Children in the NDC group had a diagnosis of cerebral palsy (CP; n = 41) or spina bifida (SB; n = 8). Parental nurturance was measured using the nurturance subscale of the Parenting Dimensions Inventory (PDI; Power, 1991). Data were analyzed using a 2 × 2 (gender × diagnosis) analysis of covariance (ANCOVA) with child age as the covariate. As a simple main effect, parents reported more nurturing behavior toward TD girls than TD boys. However, girls with an NDC received less nurturance, thereby eliminating the gender difference in parental nurturance in the NDC sample. This pattern was reflected in the larger ANCOVA as a 2-way interaction between diagnosis and gender. Group differences in other PDI subscales were not statistically significant. This pattern of results suggests that the parents of girls with NDCs may be less nurturing toward them, thereby attenuating gender differences observed in families with TD children. Findings highlight the need for more research on the gendered dynamics in families with a child with an NDC to develop systemic models of family functioning and targeted parenting interventions for this group. (c) 2014 APA, all rights reserved.
Nuclear pore complex integrity requires Lnp1, a regulator of cortical endoplasmic reticulum
Casey, Amanda K.; Chen, Shuliang; Novick, Peter; Ferro-Novick, Susan; Wente, Susan R.
2015-01-01
The nuclear envelope (NE) and endoplasmic reticulum (ER) are components of the same contiguous membrane system and yet have distinct cellular functions. Mounting evidence suggests roles for some ER proteins in the NE for proper nuclear pore complex (NPC) structure and function. In this study, we identify a NE role in Saccharomyces cerevisiae for Lnp1 and Sey1, proteins required for proper cortical ER formation. Both lnp1Δ and sey1Δ mutants exhibit synthetic genetic interactions with mutants in genes encoding key NPC structural components. Both Lnp1 and Sey1 physically associate with other ER components that have established NPC roles, including Rtn1, Yop1, Pom33, and Per33. Of interest, lnp1Δ rtn1Δ mutants but not rtn1Δ sey1Δ mutants exhibit defects in NPC distribution. Furthermore, the essential NPC assembly factor Ndc1 has altered interactions in the absence of Sey1. Lnp1 dimerizes in vitro via its C-terminal zinc finger motif, a property that is required for proper ER structure but not NPC integrity. These findings suggest that Lnp1's role in NPC integrity is separable from functions in the ER and is linked to Ndc1 and Rtn1 interactions. PMID:26041935
Tang, Ngang Heok; Toda, Takashi
2015-01-01
ABSTRACT Upon establishment of proper kinetochore–microtubule attachment, the spindle assembly checkpoint (SAC) must be silenced to allow onset of anaphase, which is when sister chromatids segregate equally to two daughter cells. However, how proper kinetochore–microtubule attachment leads to timely anaphase onset remains elusive. Furthermore, the molecular mechanisms of chromosome movement during anaphase A remain unclear. In this study, we show that the fission yeast Alp7/TACC protein recruits a protein complex consisting of the kinesin-8 (Klp5–Klp6) and protein phosphatase 1 (PP1) to the kinetochore upon kinetochore–microtubule attachment. Accumulation of this complex at the kinetochore, on the one hand, facilitates SAC inactivation through PP1, and, on the other hand, accelerates polewards chromosome movement driven by the Klp5–Klp6 motor. We identified an alp7 mutant that had specific defects in binding to the Klp5–Klp6–PP1 complex but with normal localisation to the microtubule and kinetochore. Consistent with our proposition, this mutant shows delayed anaphase onset and decelerated chromosome movement during anaphase A. We propose that the recruitment of kinesin-8–PP1 to the kinetochore through Alp7/TACC interaction plays a crucial role in regulation of timely mitotic progression and chromosome movement during anaphase A. PMID:25472718
36 CFR 1260.38 - How does the NDC ensure the quality of declassification reviews?
Code of Federal Regulations, 2012 CFR
2012-07-01
... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false How does the NDC ensure the quality of declassification reviews? 1260.38 Section 1260.38 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The...
36 CFR 1260.38 - How does the NDC ensure the quality of declassification reviews?
Code of Federal Regulations, 2014 CFR
2014-07-01
... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false How does the NDC ensure the quality of declassification reviews? 1260.38 Section 1260.38 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The...
75 FR 9343 - Nomenclature Change Relating to the Network Distribution Center Transition
Federal Register 2010, 2011, 2012, 2013, 2014
2010-03-02
... POSTAL SERVICE 39 CFR Parts 111 and 121 Nomenclature Change Relating to the Network Distribution... (BMC) to network distribution centers (NDC), by replacing all text references to ``BMC'' with ``NDC...: Background: The BMC network was established in the 1970s to process Parcel Post[supreg], Bound Printed Matter...
76 FR 16588 - Combined Mailings of Standard Mail and Periodicals Flats
Federal Register 2010, 2011, 2012, 2013, 2014
2011-03-24
... may be combined in carrier route, 5-digit (scheme), 3-digit, ADC, and Mixed ADC bundles when prepared...-digit scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and... scheme through NDC pallets must contain at least 250 pounds of combined Standard Mail and Periodicals...
North Korea’s Foreign Policy Towards the United States
2006-09-01
NDC ),[8] which has been chaired by Kim Jong Il since 1993. Kim has been using his positions as NDC chairman and KWP General-Secretary[9] to exert...overview of North Korea’s tunnels and underground facilities, see Barbara Demick, “ N. Korea’s Ace in the Hole,” The Los Angeles Times, November 14
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yang, Lu; Zhang, Sheng; Qu, Xiaoni
Lanthanide MOFs, [Eu(TCA)(NDC)·H{sub 2}O]{sub n} (1) and [Tb(TCA)(NDC)·H{sub 2}O]{sub n} (2), have been prepared with the mixed aromatic carboxylate ligands, namely, 4,4′,4″-tricarboxytriphenylamine (H{sub 3}TCA) and 1,4-naphthalenedicarboxylate (H{sub 2}NDC). Single-crystal X-ray diffraction analysis reveals that isomorphic 1 and 2 present pillar-layered 3D framework that Eu/Tb(III) bond with carboxylate in various coordination fashions. Optical investigation indicates that the as-prepared compounds feature characteristic luminescence emission bands of Eu/Tb ions in the visible regions at room temperature. Moreover, compound 2 shows a relatively longer luminescence lifetime (τ=0.342 ms) and significantly enhanced quantum yield (Φ{sub overall}=11%) comparing with those of 1 (τ=0.335 ms, Φ{sub overall}=0.06%).more » - Graphical abstract: Synoptic: Two Ln-MOFs (Ln=Eu{sup III}, Tb{sup III}) with mixed polycarboxylate ligands present different luminescent properties. - Highlights: • Two Eu/Tb-MOFs with H{sub 3}TCA and H{sub 2}NDC ligands have been obtained. • The ancillary ligand is employed to decrease water molecule coordinate numbers. • 2displays superior quantum yield and lifetime than those of 1.« less
Escobar, Matthew A.; Franklin, Keara A.; Svensson, Å. Staffan; Salter, Michael G.; Whitelam, Garry C.; Rasmusson, Allan G.
2004-01-01
Controlled oxidation reactions catalyzed by the large, proton-pumping complexes of the respiratory chain generate an electrochemical gradient across the mitochondrial inner membrane that is harnessed for ATP production. However, several alternative respiratory pathways in plants allow the maintenance of substrate oxidation while minimizing the production of ATP. We have investigated the role of light in the regulation of these energy-dissipating pathways by transcriptional profiling of the alternative oxidase, uncoupling protein, and type II NAD(P)H dehydrogenase gene families in etiolated Arabidopsis seedlings. Expression of the nda1 and ndc1 NAD(P)H dehydrogenase genes was rapidly up-regulated by a broad range of light intensities and qualities. For both genes, light induction appears to be a direct transcriptional effect that is independent of carbon status. Mutant analyses demonstrated the involvement of two separate photoreceptor families in nda1 and ndc1 light regulation: the phytochromes (phyA and phyB) and an undetermined blue light photoreceptor. In the case of the nda1 gene, the different photoreceptor systems generate distinct kinetic induction profiles that are integrated in white light response. Primary transcriptional control of light response was localized to a 99-bp region of the nda1 promoter, which contains an I-box flanked by two GT-1 elements, an arrangement prevalent in the promoters of photosynthesis-associated genes. Light induction was specific to nda1 and ndc1. The only other substantial light effect observed was a decrease in aox2 expression. Overall, these results suggest that light directly influences the respiratory electron transport chain via photoreceptor-mediated transcriptional control, likely for supporting photosynthetic metabolism. PMID:15333756
NASA Astrophysics Data System (ADS)
Yao, Xiao-Qiang; Li, Dan-Yang; Xiao, Guo-Bin; Ma, Heng-Chang; Lei, Zi-Qiang; Liu, Jia-Cheng
2018-04-01
A new compound, {[Co(BPFI)(NDC)]H2O·0.5DMF}n (1) has been synthesized under hydrothermal condition by the self-assembly of V-shaped N-containing rigid ligand BPFI with Co(II) ions in the presence of H2NDC acid, where BPFI = 2,8-di(1H-imidazole-1-yl)dibenzo[b,d]furan, H2NDC = naphthalene-1,4-dicarboxylic acid. Compound 1 was characterized by elemental analysis, single crystal X-ray diffraction, FT-IR spectroscopy and UV-visible spectra. Structural analysis reveals that compound 1 is a unique dinuclear Co-based 2D (4,4) layer structure decorated with parallel double chains. In addition, magnetic study reveals the existence of antiferromagnetic coupling interactions between the Co(II) ions within the dinuclear unit of 1.
NASA Astrophysics Data System (ADS)
Asada, M.; Suzuki, S.; Fukuma, T.
2017-11-01
The temperature dependences of output power, oscillation frequency, and current-voltage curve are measured for resonant-tunneling-diode terahertz (THz) oscillators. The output power largely changes with temperature owing to the change in Ohmic loss. In contrast to the output power, the oscillation frequency and current-voltage curve are almost insensitive to temperature. The measured temperature dependence of output power is compared with the theoretical calculation including the negative differential conductance (NDC) as a fitting parameter assumed to be independent of temperature. Very good agreement was obtained between the measurement and calculation, and the NDC in the THz frequency region is estimated. The results show that the absolute values of NDC in the THz region significantly decrease relative to that at DC, and increases with increasing frequency in the measured frequency range.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Andarini, Mellissa; Lazim, Azwan
This study focuses on hydrogel as nano template to produce iron nanoparticles (FeNps). Radical polymerization was used to synthesize the hydrogel from nata de coco (NDC-g-PAA). Ferrocenium (FcCL) with 1 × 10{sup −4} g/ml has successfully incorporated with NDC-g-PAA hydrogel system and reduce using sodium hydroxide (NaOH) at different concentrations. Transmission electron microscopy (TEM) result demonstrates that the size of FeNps produced was about 5 – 20 nm. Morphological analysis of hydrogel is carried out by scanning electron microscopy (SEM), SEM-EDEX is used to determine percentage of iron (Fe) in hydrogel. The results offer a wide range of application inmore » various areas, especially the use of hydrogel system as a responsive template.« less
Karanjkar, Pranav U.; Burt, Samuel P.; Chen, Xiaoli; ...
2016-09-12
Tetrahydropyran-2-methanol undergoes selective C–O–C hydrogenolysis to produce 1,6-hexanediol using a bifunctional RhRe (reducible metal with an oxophilic promoter) catalyst supported on Vulcan XC-72 carbon (VXC) with >90% selectivity. This RhRe/VXC catalyst is stable over 40 h of reaction in a continuous flow fixed bed reactor. The hydrogenolysis activity of RhRe/VXC is two orders-of-magnitude higher than that of RhRe supported on Norit Darco 12X40 activated carbon (NDC). STEM–EDS analysis reveals that, compared to the RhRe/VXC catalyst, the Re and Rh component metals are segregated on the surface of the low activity RhRe/NDC catalyst, suggesting that Rh and Re in close proximitymore » (“bimetallic” particles) are required for an active hydrogenolysis catalyst. Differences in metal distribution on the carbon surfaces are, in turn, linked to the properties of the carbons: NDC has both a higher surface area and surface oxygen content. Thus, the low areal density of Rh and Re precursors on the high area NDC and/or interactions of the precursors with its O functional groups may interfere with the formation of the bimetallic species required for an active catalyst.« less
NASA Astrophysics Data System (ADS)
Tsuruoka, Takaaki; Inoue, Kohei; Miyanaga, Ayumi; Tobiishi, Kaho; Ohhashi, Takashi; Hata, Manami; Takashima, Yohei; Akamatsu, Kensuke
2018-04-01
Crystal conversion of metal-organic frameworks (MOFs) between different crystal topologies on a polymer substrate has been successfully achieved by localized dissolution of MOF crystals followed by a rapid self-assembly of framework components. Upon addition of the desired organic linkers to the reaction system containing MOF crystals on the substrate, reversible crystal conversion between the [Cu2(btc)3]n and [Cu2(ndc)2(dabco)]n frameworks (btc = 1,3,5-benzene tricarboxylate, ndc = 1,4-naphthalene dicarboxylate, dabco = 1,4-diazabicyclo[2.2.2]octane) could be routinely achieved in high yields. Most surprisingly, in the case of conversion from the [Cu2(ndc)2(dabco)]n to [Cu2(btc)3]n frameworks, the [Cu2(btc)3]n crystals with unique shapes (cuboctahedron and truncated cube) could be prepared using butanol as a reaction medium.
Evaluation of the Sensitivity and Signal Response of the DT-702 LiF:Mg,Cu,P TLD
2007-06-27
energy stored from the radiation interactions that occurs prior to the TLD being read. Electrons can absorb additional energy from sources other...thermoluminescent dosimetry , annealing is the 24 process used to clear any radiation exposure information from a TLD , preparing it for reuse...702 four-chip TLDs were obtained from the Naval Dosimetry Center (NDC), Bethesda, MD. Each card was tested by Thermo prior to delivery to NDC to
2013-01-01
underground, cross-border tunnels to attack high-value targets like command and control nodes or air bases. Theater Ballistic Missiles. North Korea has...fomenting unrest and revolution. Command and Control. The DPRK National Defense Commission ( NDC ) is the symbolic nominal authority over the North’s...and control is exercised by its subordinate General Staff Department. The 1992 constitution gives control of the North’s military to the NDC , and
Hot electrons injection in carbon nanotubes under the influence of quasi-static ac-field
NASA Astrophysics Data System (ADS)
Amekpewu, M.; Mensah, S. Y.; Musah, R.; Mensah, N. G.; Abukari, S. S.; Dompreh, K. A.
2016-07-01
The theory of hot electrons injection in carbon nanotubes (CNTs) where both dc electric field (Ez), and a quasi-static ac field exist simultaneously (i.e. when the frequency ω of ac field is much less than the scattering frequency v (ω ⪡ v or ωτ ⪡ 1, v =τ-1) where τ is relaxation time) is studied. The investigation is done theoretically by solving semi-classical Boltzmann transport equation with and without the presence of the hot electrons source to derive the current densities. Plots of the normalized current density versus dc field (Ez) applied along the axis of the CNTs in the presence and absence of hot electrons reveal ohmic conductivity initially and finally negative differential conductivity (NDC) provided ωτ ⪡ 1 (i.e. quasi- static case). With strong enough axial injection of the hot electrons, there is a switch from NDC to positive differential conductivity (PDC) about Ez ≥ 75 kV / cm and Ez ≥ 140 kV / cm for a zigzag CNT and an armchair CNT respectively. Thus, the most important tough problem for NDC region which is the space charge instabilities can be suppressed due to the switch from the NDC behaviour to the PDC behaviour predicting a potential generation of terahertz radiations whose applications are relevance in current-day technology, industry, and research.
Fatihi, Abdelhak; Latimer, Scott; Schmollinger, Stefan; Block, Anna; Dussault, Patrick H.; Vermaas, Wim F.J.; Merchant, Sabeeha S.; Basset, Gilles J.
2015-01-01
Mutation of Arabidopsis thaliana NAD(P)H DEHYDROGENASE C1 (NDC1; At5g08740) results in the accumulation of demethylphylloquinone, a late biosynthetic intermediate of vitamin K1. Gene coexpression and phylogenomics analyses showed that conserved functional associations occur between vitamin K biosynthesis and NDC1 homologs throughout the prokaryotic and eukaryotic lineages. Deletion of Synechocystis ndbB, which encodes for one such homolog, resulted in the same defects as those observed in the cyanobacterial demethylnaphthoquinone methyltransferase knockout. Chemical modeling and assay of purified demethylnaphthoquinone methyltransferase demonstrated that, by virtue of the strong electrophilic nature of S-adenosyl-l-methionine, the transmethylation of the demethylated precursor of vitamin K is strictly dependent on the reduced form of its naphthoquinone ring. NDC1 was shown to catalyze such a prerequisite reduction by using NADPH and demethylphylloquinone as substrates and flavine adenine dinucleotide as a cofactor. NDC1 displayed Michaelis-Menten kinetics and was markedly inhibited by dicumarol, a competitive inhibitor of naphthoquinone oxidoreductases. These data demonstrate that the reduction of the demethylnaphthoquinone ring represents an authentic step in the biosynthetic pathway of vitamin K, that this reaction is enzymatically driven, and that a selection pressure is operating to retain type II NAD(P)H dehydrogenases in this process. PMID:26023160
Alfassy, Omri S.; Cohen, Itamar; Reiss, Yuval; Tirosh, Boaz; Ravid, Tommer
2013-01-01
Protein elimination by the ubiquitin-proteasome system requires the presence of a cis-acting degradation signal. Efforts to discern degradation signals of misfolded proteasome substrates thus far revealed a general mechanism whereby the exposure of cryptic hydrophobic motifs provides a degradation determinant. We have previously characterized such a determinant, employing the yeast kinetochore protein Ndc10 as a model substrate. Ndc10 is essentially a stable protein that is rapidly degraded upon exposure of a hydrophobic motif located at the C-terminal region. The degradation motif comprises two distinct and essential elements: DegA, encompassing two amphipathic helices, and DegB, a hydrophobic sequence within the loosely structured C-terminal tail of Ndc10. Here we show that the hydrophobic nature of DegB is irrelevant for the ubiquitylation of substrates containing the Ndc10 degradation motif, but is essential for proteasomal degradation. Mutant DegB, in which the hydrophobic sequence was disrupted, acted as a dominant degradation inhibitory element when expressed at the C-terminal regions of ubiquitin-dependent and -independent substrates of the 26S proteasome. This mutant stabilized substrates in both yeast and mammalian cells, indicative of a modular recognition moiety. The dominant function of the mutant DegB provides a powerful experimental tool for evaluating the physiological implications of stabilization of specific proteasome substrates in intact cells and for studying the associated pathological effects. PMID:23519465
Chemical and neuropathological analyses of an Alzheimer’s disease patient treated with solanezumab
Roher, Alex E; Maarouf, Chera L; Kokjohn, Tyler A; Belden, Christine; Serrano, Geidy; Sabbagh, Marwan S; Beach, Thomas G
2016-01-01
Introduction: Based on the amyloid cascade hypothesis of Alzheimer’s disease (AD) pathogenesis, a series of clinical trials involving immunotherapies have been undertaken including infusion with the IgG1 monoclonal anti-Aβ antibody solanezumab directed against the middle of the soluble Aβ peptide. In this report, we give an account of the clinical history, psychometric testing, gross and microscopic neuropathology as well as immunochemical quantitation of soluble and insoluble Aβ peptides and other proteins of interest related to AD pathophysiology in a patient treated with solanezumab. Materials and Methods: The solanezumab-treated AD case (SOLA-AD) was compared to non-demented control (NDC, n = 5) and non-immunized AD (NI-AD, n = 5) subjects. Brain sections were stained with H&E, Thioflavine-S, Campbell-Switzer and Gallyas methods. ELISA and Western blots were used for quantification of proteins of interest. Results: The SOLA-AD subject’s neuropathology and biochemistry differed sharply from the NDC and NI-AD groups. The SOLA-AD case had copious numbers of amyloid laden blood vessels in all areas of the cerebral cortex, from leptomeningeal perforating arteries to arteriolar deposits which attained the cerebral amyloid angiopathy (CAA) maximum score of 12. In contrast, the maximum CAA for the NI-AD cases averaged a total of 3.6, while the NDC cases only reached 0.75. The SOLA-AD subject had 4.4-fold more soluble Aβ40 and 5.6-fold more insoluble Aβ40 in the frontal lobe compared to NI-AD cases. In the temporal lobe of the SOLA-AD case, the soluble Aβ40 was 80-fold increased, and the insoluble Aβ40 was 13-fold more abundant compared to the non-immunized AD cases. Both soluble and insoluble Aβ42 levels were not dramatically different between the SOLA-AD and NI-AD cohort. Discussion: Solanezumab immunotherapy provided no apparent relief in the clinical evolution of dementia in this particular AD patient, since there was a continuous cognitive deterioration and full expression of amyloid deposition and neuropathology. PMID:27725918
Li, Zhaoqiang; Yin, Longwei
2015-02-25
Nitrogen-doped carbon (NDC) spheres with abundant 22 nm mesopores and 0.5 nm micropores are obtained by directly carbonization of nitrogen-contained metal organic framework (MOF) nanocrystals. Large S8 and small S2-4 molecules are successfully infiltrated into 22 nm mesopores and 0.5 nm micropores, respectively. We successfully investigate the effect of sulfur immobilization in mesopores and micropores on the electrochemical performance of lithium-sulfur (Li-S) battery based on NDC-sulfur hybrid cathodes. The large S8 molecules in 22 nm mesopores can be removed by a prolonged heat treatment, with only small molecules of S2-4 immobilized in micropores of NDC matrices. The NDC/S2-4 hybrid exhibits excellent cycling performance, high Coulombic efficiency, and good rate capability as cathode for Li-S batteries. The confinement of smaller S2-4 molecules in the micropores of NDS efficiently avoids the loss of active sulfur and formation of soluble high-order Li polysulfides. The porous carbon can buffer the volume expansion and contraction changes, promising a stable structure for cathode. Furthermore, N doping in MOF-derived carbon not only facilitates the fast charge transfer but also is helpful in building a stronger interaction between carbon and sulfur, strengthening immobilization ability of S2-4 in micropores. The NDS-sulfur hybrid cathode exhibits a reversible capacity of 936.5 mAh g(-1) at 100th cycle with a Coulombic efficiency of 100% under a current density of 335 mA g(-1). It displays a superior rate capability performance, delivering a capacity of 632 mAh g(-1) at a high rate of 5 A g(-1). This uniquely porous NDC derived from MOF nanocrystals could be applied in related high-energy storage devices.
Decreased NURR1 gene expression in patients with Parkinson’s disease
Le, Weidong; Pan, Tianhong; Huang, Maosheng; Xu, Pingyi; Xie, Wenjie; Zhu, Wen; Zhang, Xiong; Deng, Hao; Jankovic, Joseph
2008-01-01
NURR1 is a transcription factor essential for the development, survival, and functional maintenance of midbrain dopaminergic (DAergic) neurons and NURR1 is a potential susceptibility gene for Parkinson’s disease (PD). To determine whether NURR1 gene expression is altered in patients with PD we measured its expression in human peripheral blood lymphocytes (PBL) in 278 patients with PD, 166 healthy controls (HC), and 256 neurological disease controls (NDC) by quantitative real-time PCR. NURR1 gene expression was significantly decreased in patients with PD (particularly those with family history of PD) as compared with HC (p < 0.01) and also as compared with NDC (p < 0.05). There was no significant difference in NURR1 gene expression among PD patients with or without anti-PD medications. When adjusted for gender, age, and ethnicity, lower levels of NURR1 gene expression were associated with significantly increased risk for PD in women, in patients 60 years old or older, and in patients of Caucasian origin. The observed reduction in PBL NURR1 gene expression indicates possible systemic involvement in PD, and the finding may help identify individuals with PD and other disorders associated with impaired central DAergic system. PMID:18684475
Goshima, G; Yanagida, M
2000-03-17
Sister kinetochores are bioriented toward the spindle poles in higher eukaryotic prometaphase before chromosome segregation. We show that, in budding yeast, the sister kinetochores are separated in the very early spindle, while the sister arms remain associated. Biorientation of the separated kinetochores is achieved already after replication. Mtw1p, a homolog of fission yeast Mis12 required for biorientation, locates at the centromeres in an Ndc10p-dependent manner. Mtw1p and the sequences 1.8 and 3.8 kb from CEN3 and CEN15, respectively, behave like the precociously separated kinetochores, whereas the sequences 23 and 35 kb distant from CEN3 and CEN5 previously used as the centromere markers behave like a part of the arm. Mtw1p and Ndc10p are identically located except for additional spindle localization of Ndc10p. A model explaining small centromeres and early spindle formation in budding yeast is proposed.
Graglia, Micaela; Pampel, Jonas; Hantke, Tina; Fellinger, Tim-Patrick; Esposito, Davide
2016-04-26
The use of lignin as a precursor for the synthesis of materials is nowadays considered very interesting from a sustainability standpoint. Here we illustrate the synthesis of a micro-, meso-, and macroporous nitrogen-doped carbon (NDC) using lignin extracted from beech wood via alkaline hydrothermal treatment and successively functionalized via aromatic nitration. The so obtained material is thus carbonized in the eutectic salt melt KCl/ZnCl2. The final NDC shows an excellent activity as electrocatalyst for the oxygen reduction reaction.
The Emissions Scenarios Portal: Visualizing Low-Carbon Pathways for the 21st Century
NASA Astrophysics Data System (ADS)
Hennig, R. J.; Friedrich, J.; Ge, M.; Mountford, H.; Fransen, T.; Altamirano, J. C.; Thanawala, Z.; Arcipowska, A.
2017-12-01
The Emissions Scenarios Portal (ESP) is a newly developed exploration tool for 21st century low-carbon pathways and investigation of the Nationally Determined Contributions (NDC's) that countries have put forward under the Paris Agreement. It is open to the public and aims to help achieve the goal of limiting global temperature increase to well below 2 degrees Celsius above pre-industrial levels by enhancing access to high-quality, up-to-date scenario information. It can guide users to set ambitious, realistic emission mitigation goals and understand what these goals imply for different sectors of the economy. Data will be integrated from a wide variety of economic and energy-system models with results from both national models as well as globally integrated assessment models (IAM's) and countries biennial update reports (BUR's). This information can support policy and investment decision making that will lead to a low carbon future. It is designed to help find answers to questions such as "Are the NDC's enough to put the world on a 2DC track?", "What do NDC's imply for different sectors of the economy under different assumptions?" or "What are good ways to increase ambition beyond NDC's?". The portal strives to achieve both inter-comparability across a wide range of different models and nationally reported scenarios, as well as flexibility to allow modelers to bring out the strengths and purpose of their model on the platform. Furthermore, it aims to enhance standardized and transparent reporting of emissions scenarios and relevant metadata, assumptions and results to improve understanding, accessibility and impact of the scenarios. On the data side, these rivaling objectives present interesting challenges for both the collection and communication of the data and in this presentation we will present some of our ideas for tackling these. This project will be part of Climate Watch, a new data platform developed jointly by the World Resources Institute and the NDC Partnership in collaboration with GIZ, UNFCCC, World Bank, and Climate Analytics. See also Abstract ID# 231913 for more information on Climate Watch.
Park, Inai; Lee, Hae-ock; Choi, Eunhee; Lee, Yoo-Kyung; Kwon, Mi-Sun; Min, Jaewon; Park, Pil-Gu; Lee, Seonju; Kong, Young-Yun; Gong, Gyungyub
2013-01-01
BubR1 acetylation is essential in mitosis. Mice heterozygous for the acetylation-deficient BubR1 allele (K243R/+) spontaneously developed tumors with massive chromosome missegregations. K243R/+ mouse embryonic fibroblasts (MEFs) exhibited a weakened spindle assembly checkpoint (SAC) with shortened mitotic timing. The generation of the SAC signal was intact, as Mad2 localization to the unattached kinetochore (KT) was unaltered; however, because of the premature degradation of K243R-BubR1, the mitotic checkpoint complex disassociated prematurely in the nocodazole-treated condition, suggesting that maintenance of the SAC is compromised. BubR1 acetylation was also required to counteract excessive Aurora B activity at the KT for stable chromosome–spindle attachments. The association of acetylation-deficient BubR1 with PP2A-B56α phosphatase was reduced, and the phosphorylated Ndc80 at the KT was elevated in K243R/+ MEFs. In relation, there was a marked increase of micronuclei and p53 mutation was frequently detected in primary tumors of K243R/+ mice. Collectively, the combined effects of failure in chromosome–spindle attachment and weakened SAC cause genetic instability and cancer in K243R/+ mice. PMID:23878276
NASA Astrophysics Data System (ADS)
Zhu, Yajing; Wang, Li; Chen, Xiaodong; Wang, Pengcheng; Fan, Yong; Zhang, Ping
2017-07-01
A series of novel isostructural 3D lanthanide metal-organic frameworks {[Ln2(NDC)3(H2O)4]·(DMF)4}n (Ln=Eu(1), Gd(2), Tb(3), Er(4), Yb(5), Dy(6), Y(7), Lu(8), H2NDC =2,6-Naphthalenedicarboxylic acid, DMF=N,N-dimethylformamide) with a rhombic channel along the b axis and high thermal stabilities, have been successfully synthesized under solvothermal conditions. The network can be described as 2, 4, 5-connected net with Schäfli symbol of (42.62.82)2(42.63.85)2(6). Luminescent studies illustrate that 1, 2, 7 and 8 exhibit strong luminescent emitting of the corresponding Ln(III) centers in the visible range, while 5 shows near-infrared range (NIR) luminescence. Further studies of 1 and 2A (activated product of 2) show that 1 displays good stability in different solvents and excellent fluorescence sensing for organic solvent small molecules and 2A ([Gd2(NDC)3(H2O)4]n) exhibits good adsorption capacity for organic dyes in water, especially for crystal violet.
NASA Astrophysics Data System (ADS)
Kagan, M. Yu.; Aksenov, S. V.
2018-04-01
The description of quantum transport in a quadruple quantum-dot structure (QQD) is proposed taking into account the Coulomb correlations and nonzero bias voltages. To achieve this goal the combination of nonequilibrium Green's functions and equation-of-motion technique is used. It is shown that the anisotropy of kinetic processes in the QQD leads to negative differential conductance (NDC). The reason of the effect is an interplay of the Fano resonances which are induced by the interdot Coulomb correlations. Different ways to increase the peak-to-valley ratio related to the observed NDC are discussed.
NASA Astrophysics Data System (ADS)
Brandt, Patric; Herold, Martin; Rufino, Mariana C.
2018-03-01
Reducing greenhouse gas (GHG) emissions from agriculture has become a critical target in national climate change policies. More than 80% of the countries in Sub-Saharan Africa (SSA) refer to the reduction of agricultural emissions, including livestock, in their nationally determined contribution (NDC) to mitigate climate change. The livestock sector in Kenya contributes largely to the gross domestic product and to GHG emissions from the land use sector. The government has recently pledged in its NDC to curb total GHG emissions by 30% by 2030. Quantifying and linking the mitigation potential of farm practices to national targets is required to support realistically the implementation of NDCs. Improvements in feed and manure management represent promising mitigation options for dairy production. This study aimed (i) to assess mitigation and food production benefits of feed and manure management scenarios, including land use changes covering Kenya’s entire dairy production region and (ii) to analyse the contribution of these practices to national targets on milk production and mitigation, and their biophysical feasibility given the availability of arable land. The results indicate that improving forage quality by increasing the use of Napier grass and supplementing dairy concentrates supports Kenya’s NDC target, reduces emission intensities by 26%-31%, partially achieves the national milk productivity target for 2030 by 38%-41%, and shows high feasibility given the availability of arable land. Covering manure heaps may reduce emissions from manure management by 68%. In contrast, including maize silage in cattle diets would not reduce emission intensities due to the risk of ten-fold higher emissions from the conversion of land required to grow additional maize. The shortage of arable land may render the implementation of these improved feed practices largely infeasible. This assessment provides the first quantitative estimates of the potential of feed intensification and manure management to mitigate GHG emissions and to increase milk yields at sectoral-level and at a high spatial resolution for an SSA country. The scientific evidence is tailored to support actual policy and decision-making processes at the national level, such as ‘Nationally Appropriate Mitigation Actions’. Linking feed intensification and manure management strategies with spatially-explicit estimates of mitigation and food production to national targets may help the sector to access climate financing while contributing to food security.
The mammalian INO80 chromatin remodeling complex is required for replication stress recovery
Vassileva, Ivelina; Yanakieva, Iskra; Peycheva, Michaela; Gospodinov, Anastas; Anachkova, Boyka
2014-01-01
A number of studies have implicated the yeast INO80 chromatin remodeling complex in DNA replication, but the function of the human INO80 complex during S phase remains poorly understood. Here, we have systematically investigated the involvement of the catalytic subunit of the human INO80 complex during unchallenged replication and under replication stress by following the effects of its depletion on cell survival, S-phase checkpoint activation, the fate of individual replication forks, and the consequences of fork collapse. We report that INO80 was specifically needed for efficient replication elongation, while it was not required for initiation of replication. In the absence of the Ino80 protein, cells became hypersensitive to hydroxyurea and displayed hyperactive ATR-Chk1 signaling. Using bulk and fiber labeling of DNA, we found that cells deficient for Ino80 and Arp8 had impaired replication restart after treatment with replication inhibitors and accumulated double-strand breaks as evidenced by the formation of γ-H2AX and Rad51 foci. These data indicate that under conditions of replication stress mammalian INO80 protects stalled forks from collapsing and allows their subsequent restart. PMID:25016522
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Zhao-Feng; Tan, Bin; University of Chinese Academy of Sciences, Beijing 100049
2015-03-15
A magnesium metal-organic framework compound, namely [NH{sub 2}(CH{sub 3}){sub 2}][Mg{sub 3}(NDC){sub 2.5}(HCO{sub 2}){sub 2}(DMF){sub 0.75}(H{sub 2}O){sub 0.25}]·1.25DMF·0.75H{sub 2}O (1) (H{sub 2}NDC=1,4-naphthalene dicarboxylic acid, DMF=N,N′-dimethylformamide), has been synthesized in solvothermal conditions and structurally characterized. It features a three-dimensionally anionic framework with aligned channels parallel to the b-axis. Luminescent studies indicated that it showed significant luminescence quenching for carbon disulfide (CS{sub 2}) and nitrobenzene after being activated, at a content of only 3.0 and 0.1 vol% in DMF, respectively. In addition, the activated sample showed sensitive luminescence quenching for 1,3,5-trinitrophenol with a low concentration of 5×10{sup −5} mol/L. - Graphical abstract: Presentedmore » is a microporous 3D Mg-MOF, namely, [NH{sub 2}(CH{sub 3}){sub 2}][Mg{sub 3}(NDC){sub 2.5}(HCO{sub 2}){sub 2}(DMF){sub 0.75}(H{sub 2}O){sub 0.25}]·1.25DMF·0.75H{sub 2}O (1) (H{sub 2}NDC=1,4-naphthalene dicarboxylic acid) showing significant luminescence quenching for carbon disulfide and nitrobenzene. - Highlights: • A microporous 3D metal-organic framework based on Mg. • The compound shows significant luminescence quenching for CS{sub 2} and nitrobenzene after activated. • The compound shows sensitive luminescence quenching for 1,3,5-trinitrophenol with a low concentration of 5×10{sup −5} mol/L.« less
NASA Astrophysics Data System (ADS)
Martinez-Garzon, Patricia; Kwiatek, Grzegorz; Bohnhoff, Marco; Dresen, Georg
2017-04-01
Improving estimates of seismic hazard associated to reservoir stimulation requires advanced understanding of the physical processes governing induced seismicity, which can be better achieved by carefully processing large datasets. To this end, we investigate source-type processes (shear/tensile/compaction) and rupture geometries with respect to the local stress field using seismicity from The Geysers (TG) and Salton Sea geothermal reservoirs, California. Analysis of 869 well-constrained full moment tensors (MW 0.8-3.5) at TG reveals significant non-double-couple (NDC) components (>25%) for 65% of the events and remarkably diversity in the faulting mechanisms. Volumetric deformation is clearly governed by injection rates with larger NDC components observed near injection wells and during high injection periods. The overall volumetric deformation from the moment tensors increases with time, possibly reflecting a reservoir pore pressure increase after several years of fluid injection with no significant production nearby. The obtained source mechanisms and fault orientations are magnitude-dependent and vary significantly between faulting regimes. Normal faulting events (MW < 2) reveal substantial NDC components indicating dilatancy, and they occur on varying fault orientations. In contrast, strike-slip events dominantly reveal a double-couple source, larger magnitudes (MW > 2) and mostly occur on optimally oriented faults with respect to the local stress field. NDC components indicating closure of cracks and pore spaces in the source region are found for reverse faulting events with MW > 2.5. Our findings from TG are generally consistent with preliminary source-type results from a reduced subset of well-recorded seismicity at the Salton Sea geothermal reservoir. Combined results imply that source processes and magnitudes of geothermal-induced seismicity are strongly affected by and systematically related to the hydraulic operations and the local stress state.
Chun, Hyungphil; Dybtsev, Danil N; Kim, Hyunuk; Kim, Kimoon
2005-06-06
A systematic modulation of organic ligands connecting dinuclear paddle-wheel motifs leads to a series of isomorphous metal-organic porous materials that have a three-dimensional connectivity and interconnected pores. Aromatic dicarboxylates such as 1,4-benzenedicarboxylate (1,4-bdc), tetramethylterephthalate (tmbdc), 1,4-naphthalenedicarboxylate (1,4-ndc), tetrafluoroterephthalate (tfbdc), or 2,6-naphthalenedicarboxylate (2,6-ndc) are linear linkers that form two-dimensional layers, and diamine ligands, 4-diazabicyclo[2.2.2]octane (dabco) or 4,4'-dipyridyl (bpy), coordinate at both sides of Zn(2) paddle-wheel units to bridge the layers vertically. The resulting open frameworks [Zn(2)(1,4-bdc)(2)(dabco)] (1), [Zn(2)(1,4-bdc)(tmbdc)(dabco)] (2), [Zn(2)(tmbdc)(2)(dabco)] (3), [Zn(2)(1,4-ndc)(2)(dabco)] (4), [Zn(2)(tfbdc)(2)(dabco)] (5), and [Zn(2)(tmbdc)(2)(bpy)] (8) possess varying size of pores and free apertures originating from the side groups of the 1,4-bdc derivatives. [Zn(2)(1,4-bdc)(2)(bpy)] (6) and [Zn(2)(2,6-ndc)(2)(bpy)] (7) have two- and threefold interpenetrating structures, respectively. The non-interpenetrating frameworks (1-5 and 8) possess surface areas in the range of 1450-2090 m(2)g(-1) and hydrogen sorption capacities of 1.7-2.1 wt % at 78 K and 1 atm. A detailed analysis of the sorption data in conjunction with structural similarities and differences concludes that porous materials with straight channels and large openings do not perform better than those with wavy channels and small openings in terms of hydrogen storage through physisorption.
Takahashi, Yuichiro; Murakami, Hirokazu; Akiyama, Yusuke; Katoh, Yasutake; Oma, Yukako; Nishijima, Hitoshi; Shibahara, Kei-Ichi; Igarashi, Kazuhiko; Harata, Masahiko
2017-01-01
Nuclear actin family proteins, comprising of actin and actin-related proteins (Arps), are essential functional components of the multiple chromatin remodeling complexes. The INO80 chromatin remodeling complex, which is evolutionarily conserved and has roles in transcription, DNA replication and repair, consists of actin and actin-related proteins Arp4, Arp5, and Arp8. We generated Arp5 knockout (KO) and Arp8 KO cells from the human Nalm-6 pre-B cell line and used these KO cells to examine the roles of Arp5 and Arp8 in the transcriptional regulation mediated by the INO80 complex. In both of Arp5 KO and Arp8 KO cells, the oxidative stress-induced expression of HMOX1 gene, encoding for heme oxygenase-1 (HO-1), was significantly impaired. Consistent with these observations, chromatin immunoprecipitation (ChIP) assay revealed that oxidative stress caused an increase in the binding of the INO80 complex to the regulatory sites of HMOX1 in wild-type cells. The binding of INO80 complex to chromatin was reduced in Arp8 KO cells compared to that in the wild-type cells. On the other hand, the binding of INO80 complex to chromatin in Arp5 KO cells was similar to that in the wild-type cells even under the oxidative stress condition. However, both remodeling of chromatin at the HMOX1 regulatory sites and binding of a transcriptional activator to these sites were impaired in Arp5 KO cells, indicating that Arp5 is required for the activation of the INO80 complex. Collectively, these results suggested that these nuclear Arps play indispensable roles in the function of the INO80 chromatin remodeling complex.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sugimasa, Hironobu; Taniue, Kenzui; Kurimoto, Akiko
2015-03-27
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a multi-functional protein involved in transcription, mRNA splicing, mRNA stabilization and translation. Although hnRNP K has been suggested to play a role in the development of many cancers, its molecular function in colorectal cancer has remained elusive. Here we show that hnRNP K plays an important role in the mitotic process in HCT116 colon cancer cells. Furthermore, we demonstrate that hnRNP K directly transactivates the NUF2 gene, the product of which is a component of the NDC80 kinetochore complex and which is known to be critical for a stable spindle microtubule-kinetochore attachment. Inmore » addition, knockdown of both hnRNP K and NUF2 caused failure in metaphase chromosome alignment and drastic decrease in the growth of colon cancer cells. These results suggest that the hnRNP K-NUF2 axis is important for the mitotic process and proliferation of colon cancer cells and that this axis could be a target for the therapy of colon cancer. - Highlights: • hnRNP K is required for the tumorigenicity of colon cancer cells. • hnRNP K binds to the promoter region of NUF2 and activates its transcription. • NUF2 expression is correlated with hnRNP K expression in colorectal cancer tissue. • hnRNP K and NUF2 are required for metaphase chromosome alignment. • The hnRNP K-NUF2 axis is important for the proliferation of colon cancer cells.« less
Single molecular orientation switching of an endohedral metallofullerene.
Yasutake, Yuhsuke; Shi, Zujin; Okazaki, Toshiya; Shinohara, Hisanori; Majima, Yutaka
2005-06-01
The single molecular orientation switching of the Tb@C82 endohedral metallofullerene has been studied by using low-temperature ultrahigh vacuum (UHV) scanning tunneling microscopy (STM). An octanethiol self-assembled monolayer (SAM) was introduced between Tb@C82 and the Au111 substrate to control the thermal rotational states of Tb@C82. Scanning tunneling spectroscopy (STS) of Tb@C82 on an octanethiol SAM at 13 K demonstrated hysteresis including negative differential conductance (NDC). This observed hysteresis and NDC is interpreted in terms of a switching of the Tb@C82 molecular orientation caused by the interaction between its electric dipole moment and an external electric field.
Dilational processes accompanying earthquakes in the Long Valley Caldera
Dreger, Douglas S.; Tkalcic, Hrvoje; Johnston, M.
2000-01-01
Regional distance seismic moment tensor determinations and broadband waveforms of moment magnitude 4.6 to 4.9 earthquakes from a November 1997 Long Valley Caldera swarm, during an inflation episode, display evidence of anomalous seismic radiation characterized by non-double couple (NDC) moment tensors with significant volumetric components. Observed coseismic dilation suggests that hydrothermal or magmatic processes are directly triggering some of the seismicity in the region. Similarity in the NDC solutions implies a common source process, and the anomalous events may have been triggered by net fault-normal stress reduction due to high-pressure fluid injection or pressurization of fluid-saturated faults due to magmatic heating.
Read, Tania L; Macpherson, Julie V
2016-01-06
Boron doped diamond (BDD) electrodes have shown considerable promise as an electrode material where many of their reported properties such as extended solvent window, low background currents, corrosion resistance, etc., arise from the catalytically inert nature of the surface. However, if during the growth process, non-diamond-carbon (NDC) becomes incorporated into the electrode matrix, the electrochemical properties will change as the surface becomes more catalytically active. As such it is important that the electrochemist is aware of the quality and resulting key electrochemical properties of the BDD electrode prior to use. This paper describes a series of characterization steps, including Raman microscopy, capacitance, solvent window and redox electrochemistry, to ascertain whether the BDD electrode contains negligible NDC i.e. negligible sp(2) carbon. One application is highlighted which takes advantage of the catalytically inert and corrosion resistant nature of an NDC-free surface i.e. stable and quantifiable local proton and hydroxide production due to water electrolysis at a BDD electrode. An approach to measuring the local pH change induced by water electrolysis using iridium oxide coated BDD electrodes is also described in detail.
Read, Tania L.; Macpherson, Julie V.
2016-01-01
Boron doped diamond (BDD) electrodes have shown considerable promise as an electrode material where many of their reported properties such as extended solvent window, low background currents, corrosion resistance, etc., arise from the catalytically inert nature of the surface. However, if during the growth process, non-diamond-carbon (NDC) becomes incorporated into the electrode matrix, the electrochemical properties will change as the surface becomes more catalytically active. As such it is important that the electrochemist is aware of the quality and resulting key electrochemical properties of the BDD electrode prior to use. This paper describes a series of characterization steps, including Raman microscopy, capacitance, solvent window and redox electrochemistry, to ascertain whether the BDD electrode contains negligible NDC i.e. negligible sp2 carbon. One application is highlighted which takes advantage of the catalytically inert and corrosion resistant nature of an NDC-free surface i.e. stable and quantifiable local proton and hydroxide production due to water electrolysis at a BDD electrode. An approach to measuring the local pH change induced by water electrolysis using iridium oxide coated BDD electrodes is also described in detail. PMID:26779959
Xue, Dong-Xu; Belmabkhout, Youssef; Shekhah, Osama; Jiang, Hao; Adil, Karim; Cairns, Amy J; Eddaoudi, Mohamed
2015-04-22
Reticular chemistry approach was successfully employed to deliberately construct new rare-earth (RE, i.e., Eu(3+), Tb(3+), and Y(3+)) fcu metal-organic frameworks (MOFs) with restricted window apertures. Controlled and selective access to the resultant contracted fcu-MOF pores permits the achievement of the requisite sorbate cutoff, ideal for selective adsorption kinetics based separation and/or molecular sieving of gases and vapors. Predetermined reaction conditions that permitted the formation in situ of the 12-connected RE hexanuclear molecular building block (MBB) and the establishment of the first RE-fcu-MOF platform, especially in the presence of 2-fluorobenzoic acid (2-FBA) as a modulator and a structure directing agent, were used to synthesize isostructural RE-1,4-NDC-fcu-MOFs based on a relatively bulkier 2-connected bridging ligand, namely 1,4-naphthalenedicarboxylate (1,4-NDC). The subsequent RE-1,4-NDC-fcu-MOF structural features, contracted windows/pores and high concentration of open metal sites combined with exceptional hydrothermal and chemical stabilities, yielded notable gas/solvent separation properties, driven mostly by adsorption kinetics as exemplified in this work for n-butane/methane, butanol/methanol, and butanol/water pair systems.
Bai, Gaobo; Zheng, Wenling; Ma, Wenli
2018-05-01
Hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC) progression may be due to a complex multi-step processes. The developmental mechanism of these processes is worth investigating for the prevention, diagnosis and therapy of HCC. The aim of the present study was to investigate the molecular mechanism underlying the progression of HCV-induced hepatocarcinogenesis. First, the dynamic gene module, consisting of key genes associated with progression between the normal stage and HCC, was identified using the Weighted Gene Co-expression Network Analysis tool from R language. By defining those genes in the module as seeds, the change of co-expression in differentially expressed gene sets in two consecutive stages of pathological progression was examined. Finally, interaction pairs of HCV viral proteins and their directly targeted proteins in the identified module were extracted from the literature and a comprehensive interaction dataset from yeast two-hybrid experiments. By combining the interactions between HCV and their targets, and protein-protein interactions in the Search Tool for the Retrieval of Interacting Genes database (STRING), the HCV-key genes interaction network was constructed and visualized using Cytoscape software 3.2. As a result, a module containing 44 key genes was identified to be associated with HCC progression, due to the dynamic features and functions of those genes in the module. Several important differentially co-expressed gene pairs were identified between non-HCC and HCC stages. In the key genes, cyclin dependent kinase 1 (CDK1), NDC80, cyclin A2 (CCNA2) and rac GTPase activating protein 1 (RACGAP1) were shown to be targeted by the HCV nonstructural proteins NS5A, NS3 and NS5B, respectively. The four genes perform an intermediary role between the HCV viral proteins and the dysfunctional module in the HCV key genes interaction network. These findings provided valuable information for understanding the mechanism of HCV-induced HCC progression and for seeking drug targets for the therapy and prevention of HCC.
Renouf, Mathieu; Marmet, Cynthia; Guy, Philippe; Fraering, Anne-Lise; Longet, Karin; Moulin, Julie; Enslen, Marc; Barron, Denis; Cavin, Christophe; Dionisi, Fabiola; Rezzi, Serge; Kochhar, Sunil; Steiling, Heike; Williamson, Gary
2010-02-01
Chlorogenic acids (CGA) are antioxidants found in coffee. They are becoming of interest for their health-promoting effects, but bioavailability in humans is not well understood. We hypothesized that adding whole milk or sugar and nondairy creamer to instant coffee might modulate the bioavailability of coffee phenolics. Nine healthy participants were asked to randomly drink, in a crossover design, instant coffee (Coffee); instant coffee and 10% whole milk (Milk); or instant coffee, sugar, and nondairy creamer already premixed (Sugar/NDC). All 3 treatments provided the same amount of total CGA (332 mg). Blood was collected for 12 h after ingestion and plasma samples treated using a liquid-liquid extraction method that included a full enzymatic cleavage to hydrolyze all CGA and conjugates into phenolic acid equivalents. Hence, we focused our liquid chromatography-Electrospray ionization-tandem MS detection and quantification on caffeic acid (CA), ferulic acid (FA), and isoferulic acid (iFA) equivalents. Compared with a regular black instant coffee, the addition of milk did not significantly alter the area under the curve (AUC), maximum plasma concentration (C(max)), or the time needed to reach C(max) (T(max)). The C(max) of CA and iFA were significantly lower and the T(max) of FA and iFA significantly longer for the Sugar/NDC group than for the Coffee group. However, the AUC did not significantly differ. As a conclusion, adding whole milk did not alter the overall bioavailability of coffee phenolic acids, whereas sugar and nondairy creamer affected the T(max) and C(max) but not the appearance of coffee phenolics in plasma.
Unraveling the multi-functional behavior in a series of Metal Organic Frameworks
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sanda, Suresh; Biswas, Soumava; Parshamoni, Srinivasulu
2015-09-15
Three new 2D/3D Metal-Organic Frameworks (MOFs), ([Zn(2,6-ndc)(aldrithiol)]·3(H{sub 2}O)){sub n} (1), ([Co(2,6-ndc)(aldrithiol)(H{sub 2}O){sub 2}]·2(H{sub 2}O)){sub n} (2), ([Cd{sub 2}(2,6-ndc){sub 2}(aldrithiol){sub 2}(H{sub 2}O){sub 2}]·(aldrithiol)·(EtOH)·3(H{sub 2}O)){sub n} (3), (2,6-ndc = 2,6-naphthalene dicarboxylic acid; aldrithiol = 4,4'-dipyridyl disulphide) have been synthesized and structurally characterized. Compounds 1 and 2 have 2D layered architectures with similar framework topology whereas 3 is a 2-fold interwoven three dimensional framework. Sorption studies reveal that compounds 1-3 selectively adsorbs CO{sub 2} over other gases and H{sub 2}O over other solvents. Proton conductivity study of compounds 1 and 2 show highest values of 6.73 x 10{sup -7} S.cm{sup -1}, 1.96 xmore » 10{sup -5} S.cm{sup -1} at 318 K and 95% RH and these values are humidity dependent. Photoluminescent properties of compounds 1 and 3 show metal perturbed (π*–π and π*-n) intra ligand charge transfer transitions. Additionally, Compound 3 also displays reversible adsorption of molecular iodine. - Graphical abstarct: Three new 2D/3D interpenetrated MOFs are synthesized and their multifunctional material properties such as adsorption, proton conduction, iodine adsorption as well as luminscence have been explored. - Highlights: • We report multifunctional material properties in a series MOFs (Compounds 1-3) • All the compounds show selective adsorption of CO{sub 2} over other gases and H{sub 2}O over other solvents. • The proton conduction property studies of all the compounds reveal the humidity dependent conductivity. • Compound 2 shows reversible adsorption of molecular iodine in the framework. • Photoluminescent properties of compounds 1 and 2 show metal perturbed intra ligand charge transfer transitions.« less
Protective effects of notoginsenoside R1 on cerebral ischemia-reperfusion injury in rats.
Zou, Shun; Zhang, Mingxiong; Feng, Limei; Zhou, Yuanfang; Li, Li; Ban, Lili
2017-12-01
The objective of this study was to investigate the protective effect of notoginsenoside R1 (NGR1) on cerebral ischemia-reperfusion injury (CIRI) in rats, and its molecular mechanism, to provide new insights into the diagnosis and treatment of CIRI. Sixty Sprague-Dawley rats were randomly divided into four groups including the sham-operation group (Sham), cerebral ischemia-reperfusion model group (CIR), NGR1 treatment group (NGR1), and nimodipine positive control group (NDC) with 15 rats each. Bilateral common carotid arteries occlusion was used to establish the rat CIRI model. The area of cerebral infarction at the end of reperfusion was calculated by triphenyl tetrazolium chloride staining. Apoptosis of hippocampal neurons in each group was detected by Annexin V/propidium iodide double staining. Hippocampal expression of brain-derived neurotrophic factor (BDNF) mRNA, and Bcl-2 and Bax protein at the end of reperfusion were measured by RT-qPCR and western blot analysis, respectively. Data were analyzed by SPSS software analysis to ensure statistical significance. At the end of reperfusion, the area of cerebral infarction in the NGR1 and NDC groups was significantly smaller than that of the CIR group. Apoptosis analysis showed that compared with the CIR group, the apoptosis rate of hippocampal neurons was significantly decreased in the NGR1 and NDC groups. RT-qPCR and western blot analysis showed that at the end of reperfusion, higher levels of BDNF mRNA and the anti-apoptotic factor, Bcl-2, and lower levels of the pro-apoptotic factor, Bax, in the hippocampus were found in the NGR1 and NDC groups compared with the CIR group. The protective effect of NGR1 on CIRI was significantly stronger than that of nimodipine. In conclusion, NGR1 can reduce the area of cerebral infarction, reduce apoptosis of hippocampal neurons, and protect rats from CIRI. Those effects were achieved by activating the expression of BDNF and Bcl-2, and by inhibiting the expression of Bax.
Nagy, Péter; Ashby, Michael T
2005-06-01
Cystine and HOCl (a neutrophil-derived oxidant) react to form an intermediate that has a half-life of ca. 5 min at pH 7.5. The intermediate subsequently decomposes to eventually yield a mixture of cystine, higher oxides of Cys, and other uncharacterized species. Spectral titrations, transitory (1)H NMR and UV-vis spectra, and the reaction properties of the intermediate are consistent with a formulation of N,N'-dichlorocystine {NDC = [-SCH(2)CH(NHCl)(CO(2)H)](2)}. The reaction of equimolar amounts of HOCl with cystine at pH 11.3 does not yield N-chlorocystine [NCC = (-O2C)(H3N+)CHCH(2)SSCH(2)CH(NHCl)(CO(2)H)] but rather a 1:1 mixture of NDC and cystine. This result could be explained by two mechanisms: rapid disproportionation of NCC to produce NDC and cystine or a faster reaction of the second equivalent of HOCl with NCC than the first equivalent of HOCl reacts with cystine. The latter mechanism is favored because of our observation by NMR spectroscopy that NDC decomposes via a species that we have assigned as NCC. Thus, disproportionation of NCC is apparently a relatively slow process. The rates of reaction of cystine(0) = [-SCH(2)CH(NH(3)(+))(CO(2)(-))](2) degrees , cystine(1-) = [((-)O(2)C)(H(2)N)CHCH(2)SSCH(2)CH(NH(3)(+))(CO(2)(-))](-), and cystine(2-) = [-SCH(2)CH(NH2)(CO2)(-))]2(2-) have been investigated, and it is clear that cystine(0) is unreactive, whereas cystine(2-) is about four times more reactive than cystine(1-). Accordingly, the following mechanism is proposed (constants for 5 degrees C): HOCl = H+ + OCl-, pK1 = 7.47; cystine(0) = cystine(1-) + H+, pK2 = 8.15; cystine(1-) = cystine(2-) + H+, pK3 = 9.00; cystine(1-) + HOCl --> NCC(1-) + H2O, k4 = 4.3(2) x 10(6) M(-1) s(-1); cystine(2-) + HOCl --> NCC(2)(-) + H2O, k5 = 1.6(2) x 10(7) M(-1) s(-1); NCC(1-) --> NCC(2-) + H+, k6 = fast; NCC(2-) + HOCl --> NDC(2-) + H2O, k7 = fast. At physiologic pH, the k4 pathway dominates. The generation of long-lived chloramine derivatives of cystine may have physiological consequences, since such compounds are known to react with nucleophiles via mechanisms that are also characteristic of HOCl, electrophilic transfer C+.
The budding yeast RSC complex maintains ploidy by promoting spindle pole body insertion.
Sing, Tina L; Hung, Minnie P; Ohnuki, Shinsuke; Suzuki, Godai; San Luis, Bryan-Joseph; McClain, Melainia; Unruh, Jay R; Yu, Zulin; Ou, Jiongwen; Marshall-Sheppard, Jesse; Huh, Won-Ki; Costanzo, Michael; Boone, Charles; Ohya, Yoshikazu; Jaspersen, Sue L; Brown, Grant W
2018-06-06
Ploidy is tightly regulated in eukaryotic cells and is critical for cell function and survival. Cells coordinate multiple pathways to ensure replicated DNA is segregated accurately to prevent abnormal changes in chromosome number. In this study, we characterize an unanticipated role for the Saccharomyces cerevisiae "remodels the structure of chromatin" (RSC) complex in ploidy maintenance. We show that deletion of any of six nonessential RSC genes causes a rapid transition from haploid to diploid DNA content because of nondisjunction events. Diploidization is accompanied by diagnostic changes in cell morphology and is stably maintained without further ploidy increases. We find that RSC promotes chromosome segregation by facilitating spindle pole body (SPB) duplication. More specifically, RSC plays a role in distributing two SPB insertion factors, Nbp1 and Ndc1, to the new SPB. Thus, we provide insight into a role for a SWI/SNF family complex in SPB duplication and ploidy maintenance. © 2018 Sing et al.
US NDC Modernization: Service Oriented Architecture Proof of Concept
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamlet, Benjamin R.; Encarnacao, Andre Villanova; Jackson, Keilan R.
2014-12-01
This report is a progress update on the US NDC Modernization Service Oriented Architecture (SOA) study describing results from a proof of concept project completed from May through September 2013. Goals for this proof of concept are 1) gain experience configuring, using, and running an Enterprise Service Bus (ESB), 2) understand the implications of wrapping existing software in standardized interfaces for use as web services, and 3) gather performance metrics for a notional seismic event monitoring pipeline implemented using services with various data access and communication patterns. The proof of concept is a follow on to a previous SOA performancemore » study. Work was performed by four undergraduate summer student interns under the guidance of Sandia staff.« less
NASA Astrophysics Data System (ADS)
Luo, Yajun; Zhang, Zhifeng; Li, Bao; Gao, Mingwei; Qiu, Yang; He, Min
2017-12-01
To obtain a large-sized, high-quality aluminum alloy billet, an advanced uniform direct chill (UDC) casting method was developed by combining annular electromagnetic stirring (A-EMS) with intercooling in the sump. The 7005 alloy was chosen to investigate the effect of UDC on grain refinement and homogeneity during normal direct chill (NDC) casting. It was concluded that the microstructure consisting of both primary α-Al phase and secondary phases becomes finer and more homogeneous for the billets prepared with UDC casting compared to those prepared with NDC casting, and the forced cooling from both the inner and outer melt under A-EMS has a measurable effect on grain refinement and homogeneity.
36 CFR 1260.32 - How is the NDC administered?
Code of Federal Regulations, 2012 CFR
2012-07-01
..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...
36 CFR 1260.32 - How is the NDC administered?
Code of Federal Regulations, 2014 CFR
2014-07-01
..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...
36 CFR § 1260.32 - How is the NDC administered?
Code of Federal Regulations, 2013 CFR
2013-07-01
..., Defense, Energy, and Homeland Security, the Attorney General, and the Director of National Intelligence... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification...
Assen, Ayalew H; Yassine, Omar; Shekhah, Osama; Eddaoudi, Mohamed; Salama, Khaled N
2017-09-22
This work reports on the fabrication and deployment of a select metal-organic framework (MOF) thin film as an advanced chemical capacitive sensor for the sensing/detection of ammonia (NH 3 ) at room temperature. Namely, the MOF thin film sensing layer consists of a rare-earth (RE) MOF (RE-fcu-MOF) deposited on a capacitive interdigitated electrode (IDE). Purposely, the chemically stable naphthalene-based RE-fcu-MOF (NDC-Y-fcu-MOF) was elected and prepared/arranged as a thin film on a prefunctionalized capacitive IDE via the solvothermal growth method. Unlike earlier realizations, the fabricated MOF-based sensor showed a notable detection sensitivity for NH 3 at concentrations down to 1 ppm, with a detection limit appraised to be around 100 ppb (at room temperature) even in the presence of humidity and/or CO 2 . Distinctly, the NDC-Y-fcu-MOF based sensor exhibited the required stability to NH 3 , in contrast to other reported MOFs, and a remarkable detection selectivity toward NH 3 vs CH 4 , NO 2 , H 2 , and C 7 H 8 . The NDC-Y-fcu-MOF based sensor exhibited excellent performance for sensing ammonia for simulated breathing system in the presence of the mixture of carbon dioxide and/or humidity (water vapor), with no major alteration in the detection signal.
A Bir1p–Sli15p Kinetochore Passenger Complex Regulates Septin Organization during Anaphase
Thomas, Scott
2007-01-01
Kinetochore–passenger complexes in metazoans have been proposed to coordinate the segregation of chromosomes in anaphase with the induction of cytokinesis. Passenger protein homologues in the budding yeast Saccharomyces cerevisiae play a critical role early in mitosis, ensuring proper biorientation of kinetochore–microtubule attachments. Our recent work has implicated the passenger protein Bir1p (Survivin) and the inner kinetochore complex centromere binding factor 3 (CBF3) in the regulation of septin dynamics during anaphase. Here, we present data that is consistent with there being multiple passenger protein complexes. Our data show that Bir1p links together a large passenger complex containing Ndc10p, Sli15p (INCENP), and Ipl1p (Aurora B) and that the interaction between Bir1p and Sli15p is specifically involved in regulating septin dynamics during anaphase. Neither conditional alleles nor mutants of BIR1 that disrupt the interaction between Bir1p and Sli15p resulted in mono-attached kinetochores, suggesting that the Bir1p–Sli15p complex functions in anaphase and independently from Sli15p–Ipl1p complexes. We present a model for how discrete passenger complexes coordinate distinct aspects of mitosis. PMID:17652458
36 CFR 1260.34 - What are the responsibilities of the NDC?
Code of Federal Regulations, 2012 CFR
2012-07-01
... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...
36 CFR 1260.34 - What are the responsibilities of the NDC?
Code of Federal Regulations, 2014 CFR
2014-07-01
... ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National Declassification... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...
DOE Office of Scientific and Technical Information (OSTI.GOV)
McElroy, W.N.; Kellogg, L.S.; Matsumoto, W.Y.
1988-05-01
This report is in response to a request from Westinghouse Hanford Company (WHC) that the PNL National Dosimetry Center (NDC) perform physics-dosimetry analyses (E > MeV) for N Reactor Pressure Tubes 2954 and 3053. As a result of these analyses, and recommendations for additional studies, two physics-dosimetry re-evaluations for Pressure Tube 1165 were also accomplished. The primary objective of Pacific Northwest Laboratories' (PNL) National Dosimetry Center (NDC) physics-dosimetry work for N Reactor was to provide FERRET-SAND II physics-dosimetry results to assist in the assessment of neutron radiation-induced changes in the physical and mechanical properties of N Reactor pressure tubes. 15more » refs., 6 figs., 5 tabs.« less
Bagraith, Karl; Chardon, Lydia; King, Robert John
2010-11-01
Although there are widely accepted and utilized models and frameworks for nondirective counseling (NDC), there is little in the way of tools or instruments designed to assist in determining whether or not a specific episode of counseling is consistent with the stated model or framework. The Counseling Progress and Depth Rating Instrument (CPDRI) was developed to evaluate counselor integrity in the use of Egan's skilled helper model in online counseling. The instrument was found to have sound internal consistency, good interrater reliability, and good face and convergent validity. The CPDRI is, therefore, proposed as a useful tool to facilitate investigation of the degree to which counselors adhere to and apply a widely used approach to NDC.
21 CFR 1308.22 - Excluded substances.
Code of Federal Regulations, 2011 CFR
2011-04-01
....C. 811(g) (1)): Excluded Nonnarcotic Products Company Trade name NDC code Form Controlled substance... TB Phenobarbital 8.00 Hawthorne Products Inc Choate's Leg Freeze LQ Chloral hydrate 246.67 Parke...
36 CFR § 1260.34 - What are the responsibilities of the NDC?
Code of Federal Regulations, 2013 CFR
2013-07-01
... RECORDS ADMINISTRATION DECLASSIFICATION DECLASSIFICATION OF NATIONAL SECURITY INFORMATION The National... databases; and (f) Storage, and related services, on a reimbursable basis, for Federal records containing...
Non-Double-Couple Component Analysis of Induced Microearthquakes in the Val D'Agri Basin (Italy)
NASA Astrophysics Data System (ADS)
Roselli, P.; Improta, L.; Saccorotti, G.
2017-12-01
In recent years it has become accepted that earthquake source can attain significant Non-Double-Couple (NDC) components. Among the driving factors of deviation from normal double-couple (DC) mechanisms there is the opening/closing of fracture networks and the activation of pre-existing faults by pore fluid pressure perturbations. This observation makes the thorough analysis of source mechanism of key importance for the understanding of withdrawal/injection induced seismicity from geothermal and hydrocarbon reservoirs, as well as of water reservoir induced seismicity. In addition to the DC component, seismic moment tensor can be decomposed into isotropic (ISO) and compensated linear vector dipole (CLVD) components. In this study we performed a careful analysis of the seismic moment tensor of induced microseismicity recorded in the Val d'Agri (Southern Apennines, Italy) focusing our attention on the NDC component. The Val d'Agri is a Quaternary extensional basin that hosts the largest onshore European oil field and a water reservoir (Pertusillo Lake impoundment) characterized by severe seasonal level oscillations. Our input data-set includes swarm-type induced micro-seismicity recorded between 2005-2006 by a high-performance network and accurately localized by a reservoir-scale local earthquake tomography. We analyze two different seismicity clusters: (i) a swarm of 69 earthquakes with 0.3 ≤ ML ≤ 1.8 induced by a wastewater disposal well of the oilfield during the initial daily injection tests (10 days); (ii) 526 earthquakes with -0.2 ≤ ML ≤ 2.7 induced by seasonal volume changes of the artificial lake. We perform the seismic moment tensor inversion by using HybridMT code. After a very accurate signal-to-noise selection and hand-made picking of P-pulses, we obtain %DC, %ISO, %CLVD for each event. DC and NDC components are analyzed and compared with the spatio-temporal distribution of seismicity, the local stress field, the injection parameters and the water level in the impoundment. We find significant NDC components and abrupt temporal variations in the %DC and %ISO components that appear linked to the extremely variable parameters of the injection tests into the disposal well.
32 CFR 2001.32 - Declassification guides.
Code of Federal Regulations, 2010 CFR
2010-07-01
... agency head or the designated senior agency official; (2) Provide the date of issuance or last review; (3... guides or detailed declassification guidance shall be submitted to the Director of the NDC in accordance...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thangavelu, Sonia G.; Cahill, Christopher L.
Four uranyl coordination polymers [UO2(C6H8O4)(H2O)2](C18H12N6)2 (1), [UO2(C8H4O4)(H2O)2](C18H12N6)2 (2), Na[(UO2)(C12H6O4)2](C18H13N6)·H2O (3), and Na[(UO2)(C16H8O4)(C6H3NO2)](C18H12N6)·H2O (4) containing aliphatic (adipic acid) or aromatic linkers (1,4-benzene dicarboxylic acid (BDC), 1,4-napthalene dicarboxylic acid (NDC), anthracene 9,10-dicarboxylic acid (ADC)) were synthesized and characterized using single crystal X-ray diffraction, powder X-ray diffraction, and luminescence spectroscopy. The π-stacking distances or the number of π–π interactions present between trispyridyltriazine (TPTZ) guests or the host framework in 1–4 may be affected by the size of the O-donor linker (adipic acid < BDC < NDC < ADC). Luminescence studies show that substitution between adipic acid and BDC influences the emission of 1more » and 2, in which the emission of 1 shows a red shift relative to that of 2. Uranyl emission was not observed in 3 and 4, and may be attributed to the position of the NDC and ADC triplet state relative to the emissive uranyl species.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Thangavelu, Sonia G.; Cahill, Christopher L.
2016-01-06
Four uranyl coordination polymers [UO2(C6H8O4)(H2O)2](C18H12N6)2 (1), [UO2(C8H4O4)(H2O)2](C18H12N6)2 (2), Na[(UO2)(C12H6O4)2](C18H13N6)·H2O (3), and Na[(UO2)(C16H8O4)(C6H3NO2)](C18H12N6)·H2O (4) containing aliphatic (adipic acid) or aromatic linkers (1,4-benzene dicarboxylic acid (BDC), 1,4-napthalene dicarboxylic acid (NDC), anthracene 9,10-dicarboxylic acid (ADC)) were synthesized and characterized using single crystal X-ray diffraction, powder X-ray diffraction, and luminescence spectroscopy. The π-stacking distances or the number of π–π interactions present between trispyridyltriazine (TPTZ) guests or the host framework in 1–4 may be affected by the size of the O-donor linker (adipic acid < BDC < NDC < ADC). Luminescence studies show that substitution between adipic acid and BDC influences the emission of 1more » and 2, in which the emission of 1 shows a red shift relative to that of 2. Uranyl emission was not observed in 3 and 4, and may be attributed to the position of the NDC and ADC triplet state relative to the emissive uranyl species.« less
42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.
Code of Federal Regulations, 2013 CFR
2013-10-01
...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...
42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.
Code of Federal Regulations, 2012 CFR
2012-10-01
...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...
42 CFR 423.2315 - Medicare Coverage Gap Discount Program Agreement.
Code of Federal Regulations, 2014 CFR
2014-10-01
...) Maintain up-to-date NDC listings with the electronic database vendors for which the manufacturer provides... under this subpart must comply with the requirements imposed by CMS or the third party administrator (as...
Nondestructive Characterization Techniques Used for Ceramic Matrix Composite Life Determination
NASA Technical Reports Server (NTRS)
Effinger, Michael; Koenig, John; Ellingson, Bill; Spohnholtz, Todd
2000-01-01
Recent results indicate that the specific damping capacity and resonant frequency measurements taken periodically during a component's lifetime is able to quantify the mechanical fatigue of CMCS. This gives hope for the potential of determining the actual and residual life of CMC materials using a combination of nondestructive techniques. If successful, then this new paradigm for life prediction of CMCs could revolutionize the approach for designing and servicing CMC components, thereby significantly reducing costs for design, development, health monitoring, and maintenance of CMC components and systems. The Nondestructive Characterization (NDC) life prediction approach would complement life prediction using micromechanics and continuum finite element models. This paper reports on the initial concept of NDC life prediction, a review of the C/SiC blisk damping data, and how changes in the specific damping capacity & ultrasonic elastic modulus data have established the concept as a possibility.
NASA Technical Reports Server (NTRS)
Effinger, Michael; Ellingson, Bill; Spohnholtz, Todd; Koenig, John
2000-01-01
Damping measurements have been taken on ceramic matrix composite (CMC) turbopump blisks in the as fabricated, post proof testing, and post turbopump testing conditions. These results indicate that damping is able to quantify fatigue of the CMC blisk. This gives hope for the potential of determining the actual and residual life of CMC materials using a combination of nondestructive techniques. If successful, then this new paradigm for life prediction of CMCs could revolutionize the approach for designing and servicing CMC components, thereby significantly reducing costs for design, development, health monitoring, and maintenance of CMC components and systems. The Nondestructive Characterization (NDC) life prediction approach would complement life prediction using micromechanics and continuum finite element models. This paper reports on the initial concept of NDC life prediction and how changes in damping and ultrasonic elastic modulus data have established the concept as a possibility.
Use of Archived Information by the United States National Data Center
NASA Astrophysics Data System (ADS)
Junek, W. N.; Pope, B. M.; Roman-Nieves, J. I.; VanDeMark, T. F.; Ichinose, G. A.; Poffenberger, A.; Woods, M. T.
2012-12-01
The United States National Data Center (US NDC) is responsible for monitoring international compliance to nuclear test ban treaties, acquiring data and data products from the International Data Center (IDC), and distributing data according to established policy. The archive of automated and reviewed event solutions residing at the US NDC is a valuable resource for assessing and improving the performance of signal detection, event formation, location, and discrimination algorithms. Numerous research initiatives are currently underway that are focused on optimizing these processes using historic waveform data and alphanumeric information. Identification of optimum station processing parameters is routinely performed through the analysis of archived waveform data. Station specific detector tuning studies produce and compare receiver operating characteristics for multiple detector configurations (e.g., detector type, filter passband) to identify an optimum set of processing parameters with an acceptable false alarm rate. Large aftershock sequences can inundate automated phase association algorithms with numerous detections that are closely spaced in time, which increases the number of false and/or mixed associations in automated event solutions and increases analyst burden. Archived waveform data and alphanumeric information are being exploited to develop an aftershock processor that will construct association templates to assist the Global Association (GA) application, reduce the number of false and merged phase associations, and lessen analyst burden. Statistical models are being developed and evaluated for potential use by the GA application for identifying and rejecting unlikely preliminary event solutions. Other uses of archived data at the US NDC include: improved event locations using empirical travel time corrections and discrimination via a statistical framework known as the event classification matrix (ECM).
NASA Astrophysics Data System (ADS)
Lee, Tae-Hee; Park, Ka-Young; Kim, Ji-Tae; Seo, Yongho; Kim, Ki Buem; Song, Sun-Ju; Park, Byoungnam; Park, Jun-Young
2015-02-01
This study focuses on mechanisms and symptoms of several simulated failure modes, which may have significant influences on the long-term durability and operational stability of intermediate temperature-solid oxide fuel cells (IT-SOFCs), including fuel/oxidation starvation by breakdown of fuel/air supply components and wet and dry cycling atmospheres. Anode-supported IT-SOFCs consisting of a Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF)-Nd0.1Ce0.9O2-δ (NDC) composite cathode with an NDC electrolyte on a Ni-NDC anode substrate are fabricated via dry-pressings followed by the co-firing method. Comprehensive and systematic research based on the failure mode and effect analysis (FMEA) of anode-supported IT-SOFCs is conducted using various electrochemical and physiochemical analysis techniques to extend our understanding of the major mechanisms of performance deterioration under SOFC operating conditions. The fuel-starvation condition in the fuel-pump failure mode causes irreversible mechanical degradation of the electrolyte and cathode interface by the dimensional expansion of the anode support due to the oxidation of Ni metal to NiO. In contrast, the BSCF cathode shows poor stability under wet and dry cycling modes of cathode air due to the strong electroactivity of SrO with H2O. On the other hand, the air-depletion phenomena under air-pump failure mode results in the recovery of cell performance during the long-term operation without the visible microstructural transformation through the reduction of anode overvoltage.
IDC Reengineering Iteration I2 Architectural Prototype Reports
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamlet, Benjamin R.
To fulfill the inception phase deliverable “Demonstration of architectural prototype“ the SNL IDC Reengineering project team is providing seven reports describing system prototyping work completed between October 2012 and October 2014as part of the SNL US NDC Modernization project.
75 FR 32229 - National Declassification Center (NDC)
Federal Register 2010, 2011, 2012, 2013, 2014
2010-06-07
...) of Executive Order 13526, Classified National Security Information, announcement is made for the... attend must be submitted to the National Declassification Center. Information may be submitted via e-mail..., Washington, DC 20408. FOR FURTHER INFORMATION CONTACT: Don McIlwain, Supervisory Archivist, National...
NASA Astrophysics Data System (ADS)
Becker, Andreas; Krysta, Monika; Auer, Matthias; Brachet, Nicolas; Ceranna, Lars; Gestermann, Nicolai; Nikkinen, Mika; Zähringer, Matthias
2010-05-01
The so-called National Data Centres (NDCs) to the Provisional Technical Secretariat of the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty (CTBT) Organization are in charge to provide for the final judgement on the CTBT relevance of explosion events encountered in the PTS International Monitoring System (IMS). The latter is a 321 stations network set-up by the PTS (to date completion level: 80%) in order to globally monitor for occurrence of CTBT relevant seismo-acoustic and radionuclide signals. In doing so, NDCs learn about any seismo-acoustic or radionuclide event by active retrieval or subscription to corresponding event lists and products provided by the International Data Centre (IDC) to the PTS. To prepare for their instrumental role in case of a CTBT relevant event, the NDCs jointly conduct annually so-called NDC Preparedness Exercises. In 2009, NDC Germany was in charge to lead the exercise and to choose a seismo-acoustic event out of the list of events provided by the PTS (Gestermann et al., EGU2010-13067). The novelty in this procedure was that also the infrasound readings and the monitoring coverage of existing (certified) radionuclide stations into the area of consideration were taken into account during the event selection process (Coyne et al., EGU2010-12660). Hence, the event finally chosen and examined took place near Kara-Zhyra mine in Eastern Kazakhstan on 28 November 2009 around 07:20:31 UTC (Event-ID 5727516). NDC Austria performed forward atmospheric transport modelling in order to predict RN measurements that should have occurred in the radionuclide IMS. In doing so the fictitious case that there would have been a release of radionuclides taking place at the same location (Wotawa and Schraik, 2010; EGU2010-4907) in a strength being typical for a non-contained nuclear explosion is examined. The stations indicated should then be analysed for their actual radionuclide readings in order to confirm the non nuclear character of the event (negative testing scenario). Obviously only stations already set up and ‘certified' of being capable of full operations, could be recruited for this. In doing so an issue was encountered with regard to the availability of RN data at certified RN stations. Despite the support to the event selection, PTS also supplied so-called data fusion bulletins that apply a method to collocate the RN and seismo-acoustic source location results (Krysta and Becker, EGU2010-10218). In this paper we demonstrate the impact of gaps in network coverage that appear due to the aforementioned reduced RN data availability for source location capacities. Network coverage assessments for the set of certified stations and the reduced set of stations actually sending data shall therefore be discussed. Furthermore, the capabilities and constraints of the data fusion method to make up for the RN source location accuracy losses related to reduced RN data availability at certified stations shall be presented.
Shamseldin, Hanan E; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S; Gleeson, Joseph G; Alkuraya, Fowzan S
2016-01-07
Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
Evaluating the implementation of RxNorm in ambulatory electronic prescriptions
Ward-Charlerie, Stacy; Rupp, Michael T; Kilbourne, John; Amin, Vishal P; Ruiz, Joshua
2016-01-01
Objective RxNorm is a standardized drug nomenclature maintained by the National Library of Medicine that has been recommended as an alternative to the National Drug Code (NDC) terminology for use in electronic prescribing. The objective of this study was to evaluate the implementation of RxNorm in ambulatory care electronic prescriptions (e-prescriptions). Methods We analyzed a random sample of 49 997 e-prescriptions that were received by 7391 locations of a national retail pharmacy chain during a single day in April 2014. The e-prescriptions in the sample were generated by 37 801 ambulatory care prescribers using 519 different e-prescribing software applications. Results We found that 97.9% of e-prescriptions in the study sample could be accurately represented by an RxNorm identifier. However, RxNorm identifiers were actually used as drug identifiers in only 16 433 (33.0%) e-prescriptions. Another 431 (2.5%) e-prescriptions that used RxNorm identifiers had a discrepancy in the corresponding Drug Database Code qualifier field or did not have a qualifier (Term Type) at all. In 10 e-prescriptions (0.06%), the free-text drug description and the RxNorm concept unique identifier pointed to completely different drug concepts, and in 7 e-prescriptions (0.04%), the NDC and RxNorm drug identifiers pointed to completely different drug concepts. Discussion The National Library of Medicine continues to enhance the RxNorm terminology and expand its scope. This study illustrates the need for technology vendors to improve their implementation of RxNorm; doing so will accelerate the adoption of RxNorm as the preferred alternative to using the NDC terminology in e-prescribing. PMID:26510879
Ponsford, J; Lee, N K; Wong, D; McKay, A; Haines, K; Alway, Y; Downing, M; Furtado, C; O'Donnell, M L
2016-04-01
Anxiety and depression are common following traumatic brain injury (TBI), often co-occurring. This study evaluated the efficacy of a 9-week cognitive behavioral therapy (CBT) program in reducing anxiety and depression and whether a three-session motivational interviewing (MI) preparatory intervention increased treatment response. A randomized parallel three-group design was employed. Following diagnosis of anxiety and/or depression using the Structured Clinical Interview for DSM-IV, 75 participants with mild-severe TBI (mean age 42.2 years, mean post-traumatic amnesia 22 days) were randomly assigned to an Adapted CBT group: (1) MI + CBT (n = 26), or (2) non-directive counseling (NDC) + CBT (n = 26); or a (3) waitlist control (WC, n = 23) group. Groups did not differ in baseline demographics, injury severity, anxiety or depression. MI and CBT interventions were guided by manuals adapted for individuals with TBI. Three CBT booster sessions were provided at week 21 to intervention groups. Using intention-to-treat analyses, random-effects regressions controlling for baseline scores revealed that Adapted CBT groups (MI + CBT and NDC + CBT) showed significantly greater reduction in anxiety on the Hospital Anxiety and Depression Scale [95% confidence interval (CI) -2.07 to -0.06] and depression on the Depression Anxiety and Stress Scale (95% CI -5.61 to -0.12) (primary outcomes), and greater gains in psychosocial functioning on Sydney Psychosocial Reintegration Scale (95% CI 0.04-3.69) (secondary outcome) over 30 weeks post-baseline relative to WC. The group receiving MI + CBT did not show greater gains than the group receiving NDC + CBT. Findings suggest that modified CBT with booster sessions over extended periods may alleviate anxiety and depression following TBI.
NASA Astrophysics Data System (ADS)
Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi; Yu, Lei; Xie, Yi-Xin; Han, Lei
2015-12-01
Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H2ndc) or 4,4‧-(hydroxymethylene)dibenzoic acid (H2hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd2(2,6-ndc)2(bpp)(DMF)]·2DMF (1) and [Cd3(hmdb)3(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional 'Lucky Clover' shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations in 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process.
NASA Astrophysics Data System (ADS)
Fan, Xin; Chen, Weiliang; Pang, Shuhua; Lu, Wei; Zhao, Yu; Liu, Zheng; Fang, Dong
2017-12-01
In the present work, asymmetric supercapacitors (ASCs) are assembled using a highly conductive N-doped nanocarbon (NDC) material derived from a polyaniline hydrogel as a cathode, and Ni foam covered with flower-like Co3O4 nanosheets (Co3O4-Ni) prepared from a zeolitic imidazolate metal-organic framework as a single precursor serves as a high gravimetric capacitance anode. At a current of 0.2 A g-1, the Co3O4-Ni electrode provides a gravimetric capacitance of 637.7 F g-1, and the NDC electrode provides a gravimetric capacitance of 359.6 F g-1. The ASC assembled with an optimal active material loading operates within a wide potential window of 0-1.1 V, and provides a high areal capacitance of 25.7 mF cm-2. The proposed ASC represents a promising strategy for designing high-performance supercapacitors.
The tunnel magnetoresistance in chains of quantum dots weakly coupled to external leads.
Weymann, Ireneusz
2010-01-13
We analyze numerically the spin-dependent transport through coherent chains of three coupled quantum dots weakly connected to external magnetic leads. In particular, using the diagrammatic technique on the Keldysh contour, we calculate the conductance, shot noise and tunnel magnetoresistance (TMR) in the sequential and cotunneling regimes. We show that transport characteristics greatly depend on the strength of the interdot Coulomb correlations, which determines the spatial distribution of the electron wavefunction in the chain. When the correlations are relatively strong, depending on the transport regime, we find both negative TMR as well as TMR enhanced above the Julliere value, accompanied with negative differential conductance (NDC) and super-Poissonian shot noise. This nontrivial behavior of tunnel magnetoresistance is associated with selection rules that govern tunneling processes and various high-spin states of the chain that are relevant for transport. For weak interdot correlations, on the other hand, the TMR is always positive and not larger than the Julliere TMR, although super-Poissonian shot noise and NDC can still be observed.
Pom121 links two essential subcomplexes of the nuclear pore complex core to the membrane
Mitchell, Jana M.; Mansfeld, Jörg; Capitanio, Juliana; Kutay, Ulrike
2010-01-01
Nuclear pore complexes (NPCs) control the movement of molecules across the nuclear envelope (NE). We investigated the molecular interactions that exist at the interface between the NPC scaffold and the pore membrane. We show that key players mediating these interactions in mammalian cells are the nucleoporins Nup155 and Nup160. Nup155 depletion massively alters NE structure, causing a dramatic decrease in NPC numbers and the improper targeting of membrane proteins to the inner nuclear membrane. The role of Nup155 in assembly is likely closely linked to events at the membrane as we show that Nup155 interacts with pore membrane proteins Pom121 and NDC1. Furthermore, we demonstrate that the N terminus of Pom121 directly binds the β-propeller regions of Nup155 and Nup160. We propose a model in which the interactions of Pom121 with Nup155 and Nup160 are predicted to assist in the formation of the nuclear pore and the anchoring of the NPC to the pore membrane. PMID:20974814
Scenario design and basic analysis of the National Data Centre Preparedness Exercise 2013
NASA Astrophysics Data System (ADS)
Ross, Ole; Ceranna, Lars; Hartmann, Gernot; Gestermann, Nicolai; Bönneman, Christian
2014-05-01
The Comprehensive Nuclear-Test-Ban Treaty (CTBT) prohibits all kinds of nuclear explosions. For the detection of treaty violations the International Monitoring System (IMS) operates stations observing seismic, hydroacoustic, and infrasound signals as well as radioisotopes in the atmosphere. While the IMS data is collected, processed and technically analyzed in the International Data Center (IDC) of the CTBT-Organization, National Data Centers (NDC) provide interpretation and advice to their government concerning suspicious detections occurring in IMS data. NDC Preparedness Exercises (NPE) are regularly performed dealing with fictitious treaty violations to practice the combined analysis of CTBT verification technologies and for the mutual exchange of information between NDC and also with the IDC. The NPE2010 and NPE2012 trigger scenarios were based on selected seismic events from the Reviewed Event Bulletin (REB) serving as starting point for fictitious Radionuclide dispersion. The main task was the identification of the original REB event and the discrimination between earthquakes and explosions as source. The scenario design of NPE2013 differs from those of previous NPEs. The waveform event selection is not constrained to events in the REB. The exercise trigger is a combination of a tempo-spatial indication pointing to a certain waveform event and simulated radionuclide concentrations generated by forward Atmospheric Transport Modelling based on a fictitious release. For the waveform event the date (4 Sept. 2013) is given and the region is communicated in a map showing the fictitious state of "Frisia" at the Coast of the North Sea in Central Europe. The synthetic radionuclide detections start in Vienna (8 Sept, I-131) and Schauinsland (11 Sept, Xe-133) with rather low activity concentrations and are most prominent in Stockholm and Spitsbergen mid of September 2013. Smaller concentrations in Asia follow later on. The potential connection between the waveform and radionuclide evidence remains unclear. The verification task is to identify the waveform event and to investigate potential sources of the radionuclide findings. Finally the potential conjunction between the sources and the CTBT-relevance of the whole picture has to be evaluated. The overall question is whether requesting an On-Site-Inspection in "Frisia" would be justified. The poster presents the NPE2013 scenario and gives a basic analysis of the initial situation concerning both waveform detections and atmospheric dispersion conditions in Central Europe in early September 2013. The full NPE2013 scenario will be presented at the NDC Workshop mid of May 2014.
76 FR 65640 - New Standards for Domestic Mailing Services
Federal Register 2010, 2011, 2012, 2013, 2014
2011-10-24
...). * * * * * [Revise item 2.2c as follows:] c. Each metered piece must bear full postage at the lowest First- Class... shape, weight, construction, and size to be considered. If the request describes a mailpiece that falls... preparation level (e.g., destination NDC pallets). c. Upon acknowledgement from the manager, Operations...
39 CFR 121.4 - Package Services.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day-zero...) Package Services mail accepted at origin before the day-zero Critical Entry Time is 3 days, for each... Center (NDC) Package Services mail accepted at origin before the day-zero Critical Entry Time is 4 days...
Verification Fit Test of Three Size Infantry Helmet
1975-01-01
consideration to the helmet designer. This result is consistent with other studies (for example, NDC Technical Report 72-52-CE, " Anthropometry of US Army...FRBQUENCY 18 * 17 * 16 * 15 * 14 * * 13 * * 12 * * * xl . * * 10 * * *S9 * * * * * ° •:i8 * * * * * S7 * * * * * * S6 * * * * * * * S5 4 * * * * * * * *I3
39 CFR 121.4 - Package Services.
Code of Federal Regulations, 2011 CFR
2011-07-01
... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day zero... origin before the day-zero Critical Entry Time is 3 days, for each remaining (non-intra-SCF) 3-digit ZIP... intra-Network Distribution Center (NDC) Package Services mail accepted at origin before the day-zero...
39 CFR 121.4 - Package Services.
Code of Federal Regulations, 2010 CFR
2010-07-01
... Center Facility (SCF) turnaround Package Services mail accepted at the origin SCF before the day zero... origin before the day-zero Critical Entry Time is 3 days, for each remaining (non-intra-SCF) 3-digit ZIP... intra-Network Distribution Center (NDC) Package Services mail accepted at origin before the day-zero...
Fokina, K V; Dainyak, M B; Nagradova, N K; Muronetz, V I
1997-09-15
The ability of D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzing the reaction of 1,3-diphosphoglycerate synthesis in human erythrocytes to form complexes with enzymes which use this metabolite as substrate (3-phosphoglycerate kinase (3-PGK) or 2,3-diphosphoglycerate mutase (2,3-DPGM)) was studied. It was found that highly active 2,3-DPGM can be extracted from human erythrocyte hemolysates in a complex with GAPDH adsorbed on Sepharose-bound anti-GAPDH antibodies at pH 6.5, the molar ratio being one 2,3-GPGM subunit per subunit of GAPDH. No complexation was, however, detected at pH 8.0. The opposite was true for the interaction between GAPDH and 3-PGK, which could be observed at pH 8.0. In experiments carried out at pH 7.4, both GAPDH x 2,3-DPGM and GAPGH x 3-PGK complexes were detected. The Kd values of the complexes determined with purified enzyme preparations were in the range 2.40-2.48 microM for both the GAPDH x 2,3-DPGM and GAPGH x 3-PGK enzyme pairs, when titrations of GAPDH covalently bound to CNBr-activated Sepharose were performed by the soluble 2,3-DPGM or 3-PGK. If, however, GAPDH adsorbed on the specific antibodies covalently bound to Sepharose was used in the titration experiments, the Kd for the GAPDH x 2,3-DPGM complex was found to be 0.54 microM, and the Kd for the GAPDH x 3-PGK complex was 0.49 microM. The concentration of 2,3-diphosphoglycerate determined after 1 h of incubation of erythrocytes in the presence of glucose was found to increase 1.5-fold if the incubation was carried out at pH 6.5, but did not change upon incubation at pH 8.0. On the other hand, the concentration of 3-phosphoglycerate after incubation at pH 8.0 was twice as large as that found after incubation at pH 6.5. The results are interpreted on the hypothesis that specific protein-protein interactions between GAPDH and 2,3-DPGM or between GAPDH and 3-PGK may play a role in determining the fate of 1,3-diphosphoglycerate produced in the GAPDH-catalyzed reaction.
Jücker, M; Feldman, R A
1996-01-01
We have used a human GM-CSF-dependent hematopoietic cell line that responds to physiological concentrations of hGM-CSF to analyze a set of signaling events that occur in normal myelopoiesis and whose deregulation may lead to leukemogenesis. Stimulation of these cells with hGM-CSF induced the assembly of multimeric complexes that contained known and novel phosphotyrosyl proteins. One of the new proteins was a major phosphotyrosyl substrate of 76-85 kDa (p80) that was directly associated with the p85 subunit of phosphatidylinositol (PI) 3-kinase through the SH2 domains of p85. p80 also associated with the beta subunit of the activated hGM-CSF receptor, and assembly of this complex correlated with activation of PI 3-kinase. A second phosphotyrosyl protein we identified, p140, associated with the Shc and Grb2 adapter proteins by direct binding to a novel phosphotyrosine-interacting domain located at the N-terminus of Shc. and to the SH3 domains of Grb2, respectively. The Shc/p140/Grb2 complex was found to be constitutively activated in acute myeloid leukemia cells, indicating that activation of this pathway may be a necessary step in the development of some leukemias. The p80/p85/PI 3-kinase and the Shc/Grb2/p140 complexes were tightly associated with Src family kinases, which were prime candidates for phosphorylation of Shc, p80, p140 and other phosphotyrosyl substrates present in these complexes. Our studies suggest that p80 and p140 may link the hGM-CSF receptor to the PI 3-kinase and Shc/Grb2/ras signaling pathways, respectively, and that abnormal activation of hGM-CSF-dependent targets may play a role in leukemogenesis.
Jücker, M; Feldman, R A
1995-11-17
Binding of human granulocyte/macrophage colony-stimulating factor (hGM-CSF) to its receptor induces the rapid activation of phosphatidylinositol-3 kinase (PI 3-kinase). As hGM-CSF receptor (hGMR) does not contain a consensus sequence for binding of PI 3-kinase, hGMR must use a distinct mechanism for its association with and activation of PI 3-kinase. Here, we describe the identification of a tyrosine-phosphorylated protein of 76-85 kDa (p80) that associates with the common beta subunit of hGMR and with the SH2 domains of the p85 subunit of PI 3-kinase in hGM-CSF-stimulated cells. Src/Yes and Lyn were tightly associated with the p80.PI 3-kinase complex, suggesting that p80 and other phosphotyrosyl proteins present in the complex were phosphorylated by Src family kinases. Tyrosine phosphorylation of p80 was only detected in hGM-CSF or human interleukin-3-stimulated cells, suggesting that activation of p80 might be specific for signaling via the common beta subunit. We postulate that p80 functions as an adapter protein that may participate in linking the hGM-CSF receptor to the PI 3-kinase signaling pathway.
Characterization of the biological activity of a potent small molecule Hec1 inhibitor TAI-1
2014-01-01
Background Hec1 (NDC80) is an integral part of the kinetochore and is overexpressed in a variety of human cancers, making it an attractive molecular target for the design of novel anticancer therapeutics. A highly potent first-in-class compound targeting Hec1, TAI-1, was identified and is characterized in this study to determine its potential as an anticancer agent for clinical utility. Methods The in vitro potency, cancer cell specificity, synergy activity, and markers for response of TAI-1 were evaluated with cell lines. Mechanism of action was confirmed with western blotting and immunofluorescent staining. The in vivo potency of TAI-1 was evaluated in three xenograft models in mice. Preliminary toxicity was evaluated in mice. Specificity to the target was tested with a kinase panel. Cardiac safety was evaluated with hERG assay. Clinical correlation was performed with human gene database. Results TAI-1 showed strong potency across a broad spectrum of tumor cells. TAI-1 disrupted Hec1-Nek2 protein interaction, led to Nek2 degradation, induced significant chromosomal misalignment in metaphase, and induced apoptotic cell death. TAI-1 was effective orally in in vivo animal models of triple negative breast cancer, colon cancer and liver cancer. Preliminary toxicity shows no effect on the body weights, organ weights, and blood indices at efficacious doses. TAI-1 shows high specificity to cancer cells and to target and had no effect on the cardiac channel hERG. TAI-1 is synergistic with doxorubicin, topotecan and paclitaxel in leukemia, breast and liver cancer cells. Sensitivity to TAI-1 was associated with the status of RB and P53 gene. Knockdown of RB and P53 in cancer cells increased sensitivity to TAI-1. Hec1-overexpressing molecular subtypes of human lung cancer were identified. Conclusions The excellent potency, safety and synergistic profiles of this potent first-in-class Hec1-targeted small molecule TAI-1 show its potential for clinically utility in anti-cancer treatment regimens. PMID:24401611
36 CFR 1260.46 - How does the Department of Defense process referrals?
Code of Federal Regulations, 2014 CFR
2014-07-01
... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false How does the Department of...
36 CFR 1260.46 - How does the Department of Defense process referrals?
Code of Federal Regulations, 2012 CFR
2012-07-01
... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false How does the Department of...
42 CFR 447.514 - Upper limits for multiple source drugs.
Code of Federal Regulations, 2010 CFR
2010-10-01
... State agency plus an amount established by CMS that is equal to 250 percent of the AMP (as computed... will consider the following additional criteria: (1) The AMP of a terminated NDC will not be used to... section, the AMP of the lowest priced therapeutically and pharmaceutically equivalent drug that is not...
North Korea: Back on the Terrorism List
2010-05-24
fabrication.” Pyongyang Korean Central Broadcasting Station, “DPRK NDC Spokesman’s Statement on ROK’s Sunken Ship Investigation Results,” May 20...underground military facilities, including tunnels and bunkers. Takashi Arimoto, Washington correspondent for the Japanese newspaper, Sankei Shimbun, has...underground tunnel with numerous assembly points that Hezbollah 71 Daniel Michaels and
Theoretical Investigation of Device Aspects of Semiconductor Superlattices.
1983-09-01
n-i-p-i devices include bulk field effect transistors, ultrasensitive or ultrafast IR photodetectors , tunable light-emitting devices, and ultrafast...transistor4 ultrasensitive or ultrafast IR photodetectors , tunable light-emitt tg devices, and ultrafast optical modulators. Particularlylppealing...differential conductivity ( NDC ) ......................... 19 3.2.2. Spontaneous and stimulated FIR emission from interlayer transitions
North Korean Civil-Military Trends: Military-First Politics to a Point
2006-09-01
to the Great Leader. Yi Yong Mu. The NDC’s impact on the formal leadership lineup was made clear by 2001, when Yi Yong Mu, vice chairman of the NDC...to be restricted, as are career bonds that could come about between officers through sequential appointments to same commands. • First time
21 CFR 801.57 - Discontinuation of legacy FDA identification numbers assigned to devices.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Discontinuation of legacy FDA identification... Device Identification § 801.57 Discontinuation of legacy FDA identification numbers assigned to devices... been assigned an FDA labeler code to facilitate use of NHRIC or NDC numbers may continue to use that...
Code of Federal Regulations, 2010 CFR
2010-07-01
... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...
Code of Federal Regulations, 2011 CFR
2011-07-01
... Facility (SCF) turnaround Standard Mail® pieces accepted at origin before the day zero Critical Entry Time... origin before the day zero Critical Entry Time is 4 days when the OPD&C/F and the ADC are the same... intra-Network Distribution Center (NDC) Standard Mail pieces accepted at origin before the day-zero...
[Effect of filial imprinting procedure on cell proliferation in the chick brain].
Komissarova, N V; Anokhin, K V
2007-01-01
In the present study we tested the hypothesis that memory formation during visual imprinting might be related to generation of new cells in the brain of newborn domestic chicks. Cell proliferation was examined in the intermediate medial mesopallium (IMM), arcopallium intermedium (AI), medial part of nidopallium and mesopallium (MNM), nidopallium dorso-caudalis (Ndc), hippocampus (Hp) and area parahippocampalis (APH), as well as in corresponding ventricular zones. Number of new cells was measured by BrdU incorporation 24 h or 7 days after training, BrdU was injected before training. 24 h after imprinting the number of BrdU-positive cells increased significantly in IMM. 7 days after training no changes were observed in IMM, while the number of new cells decreased in MNM and Ndc in comparison to the control group. These data suggest that newly generated cells in the brain of young chicks are influenced by imprinting procedure, which has opposite short-term and long-term effects. A possible reason for such double action of imprinting in contrast to conventional learning can be its additional stimulation of development of predisposition for features of natural parents.
Malcomson, Fiona C; Willis, Naomi D; Mathers, John C
2015-08-01
Epidemiological and experimental evidence suggests that non-digestible carbohydrates (NDC) including resistant starch are protective against colorectal cancer. These anti-neoplastic effects are presumed to result from the production of the SCFA, butyrate, by colonic fermentation, which binds to the G-protein-coupled receptor GPR43 to regulate inflammation and other cancer-related processes. The WNT pathway is central to the maintenance of homeostasis within the large bowel through regulation of processes such as cell proliferation and migration and is frequently aberrantly hyperactivated in colorectal cancers. Abnormal WNT signalling can lead to irregular crypt cell proliferation that favours a hyperproliferative state. Butyrate has been shown to modulate the WNT pathway positively, affecting functional outcomes such as apoptosis and proliferation. Butyrate's ability to regulate gene expression results from epigenetic mechanisms, including its role as a histone deacetylase inhibitor and through modulating DNA methylation and the expression of microRNA. We conclude that genetic and epigenetic modulation of the WNT signalling pathway may be an important mechanism through which butyrate from fermentation of resistant starch and other NDC exert their chemoprotective effects.
Full counting statistics in a serially coupled double quantum dot system with spin-orbit coupling
NASA Astrophysics Data System (ADS)
Wang, Qiang; Xue, Hai-Bin; Xie, Hai-Qing
2018-04-01
We study the full counting statistics of electron transport through a serially coupled double quantum dot (QD) system with spin-orbit coupling (SOC) weakly coupled to two electrodes. We demonstrate that the spin polarizations of the source and drain electrodes determine whether the shot noise maintains super-Poissonian distribution, and whether the sign transitions of the skewness from positive to negative values and of the kurtosis from negative to positive values take place. In particular, the interplay between the spin polarizations of the source and drain electrodes and the magnitude of the external magnetic field, can give rise to a gate-voltage-tunable strong negative differential conductance (NDC) and the shot noise in this NDC region is significantly enhanced. Importantly, for a given SOC parameter, the obvious variation of the high-order current cumulants as a function of the energy-level detuning in a certain range, especially the dip position of the Fano factor of the skewness can be used to qualitatively extract the information about the magnitude of the SOC.
NASA Astrophysics Data System (ADS)
Wotawa, Gerhard; Schraick, Irene
2010-05-01
An explosion in the Kara-Zhyra mine in Eastern Kazakhstan on 28 November 2009 around 07:20 UTC was recorded by both the CTBTO seismic and infrasound networks. This event triggered a world-wide preparedness exercise among the CTBTO National Data Centres. Within an hour after the event was selected by the German NDC, a computer program developed by NDC Austria based on weather forecasts from the European Centre for Medium-Range Weather Forecasts (ECMWF) and from the U.S. National Centers for Environmental Prediction (NCEP) was started to analyse what Radionuclide Stations of the CTBTO International Monitoring System (IMS) would be potentially affected by the release from a nuclear explosion at this place in the course of the following 3-10 days. These calculations were daily updated to consider the observed state of the atmosphere instead of the predicted one. Based on these calculations, automated and reviewed radionuclide reports from the potentially affected stations as produced by the CTBTO International Data Centre (IDC) were looked at. An additional analysis of interesting spectra was provided by the Seibersdorf Laboratories. Based on all the results coming in, no evidence whatsoever was found that the explosion in Kazakhstan was nuclear. This is in accordance with ground truth information saying that the event was caused by the detonation of more than 53 Tons of explosives as part of mining operations. A number of conclusions can be drawn from this exercise. First, the international, bilateral as well as national mechanisms and procedures in place for such an event worked smoothly. Second, the products and services from the CTBTO IDC proved to be very useful to assist the member states in their verification efforts. Last but not least, issues with the availability of data from IMS radionuclide stations do remain.
Sim, Jaeung; Yim, Haneul; Ko, Nakeun; Choi, Sang Beom; Oh, Youjin; Park, Hye Jeong; Park, SangYoun; Kim, Jaheon
2014-12-28
Three functionalized metal-organic frameworks (MOFs), MOF-205-NH2, MOF-205-NO2, and MOF-205-OBn, formulated as Zn4O(BTB)4/3(L), where BTB is benzene-1,3,5-tribenzoate and L is 1-aminonaphthalene-3,7-dicarboxylate (NDC-NH2), 1-nitronaphthalene-3,7-dicarboxylate (NDC-NO2) or 1,5-dibenzyloxy-2,6-naphthalenedicarboxylate (NDC-(OBn)2), were synthesized and their gas (H2, CO2, or CH4) adsorption properties were compared to those of the un-functionalized, parent MOF-205. Ordered structural models for MOF-205 and its derivatives were built based on the crystal structures and were subsequently used for predicting porosity properties. Although the Brunauer-Emmett-Teller (BET) surface areas of the three MOF-205 derivatives were reduced (MOF-205, 4460; MOF-205-NH2, 4330; MOF-205-NO2, 3980; MOF-205-OBn, 3470 m(2) g(-1)), all three derivatives were shown to have enhanced H2 adsorption capacities at 77 K and CO2 uptakes at 253, 273, and 298 K respectively at 1 bar in comparison with MOF-205. The results indicate the following trend in H2 adsorption: MOF-205 < MOF-205-NO2 < MOF-205-NH2 < MOF-205-OBn. MOF-205-OBn showed good ideal adsorbed solution theory (IAST) selectivity values of 6.5 for CO2/N2 (15/85 in v/v) and 2.7 for CO2/CH4 (50/50 in v/v) at 298 K. Despite the large reduction (-22%) in the surface area, MOF-205-OBn displayed comparable total volumetric CO2 (at 48 bar) and CH4 (at 35 bar) storage capacities with those of MOF-205 at 298 K: MOF-205-OBn, 305 (CO2) and 112 (CH4) cm(3) cm(-3), and for MOF-205, 307 (CO2) and 120 (CH4) cm(3) cm(-3), respectively.
Yeh, Chung-Hsin; Kuo, Pao-Lin; Wang, Ya-Yun; Wu, Ying-Yu; Chen, Mei-Feng; Lin, Ding-Yen; Lai, Tsung-Hsuan; Chiang, Han-Sun; Lin, Ying-Hung
2015-01-01
Male infertility affects approximately 50% of all infertile couples. The male-related causes of intracytoplasmic sperm injection failure include the absence of sperm, immotile or immature sperm, and sperm with structural defects such as those caused by premature chromosomal condensation and DNA damage. Our previous studies based on a knockout mice model indicated that SEPT12 proteins are critical for the terminal morphological formation of sperm. SEPT12 mutations in men result in teratozospermia and oligozospermia. In addition, the spermatozoa exhibit morphological defects of the head and tail, premature chromosomal condensation, and nuclear damage. However, the molecular functions of SEPT12 during spermatogenesis remain unclear. To determine the molecular functions of SEPT12, we applied a yeast 2-hybrid system to identify SEPT12 interactors. Seven proteins that interact with SEPT12 were identified: SEPT family proteins (SEPT4 and SEPT6), nuclear or nuclear membrane proteins (protamine 2, sperm-associated antigen 4, and NDC1 transmembrane nucleoproine), and sperm-related structural proteins (pericentriolar material 1 and obscurin-like 1). Sperm-associated antigen 4 (SPAG4; also known as SUN4) belongs to the SUN family of proteins and acts as a linker protein between nucleoskeleton and cytoskeleton proteins and localizes in the nuclear membrane. We determined that SEPT12 interacts with SPAG4 in a male germ cell line through coimmunoprecipitation. During human spermiogenesis, SEPT12 is colocalized with SPAG4 near the nuclear periphery in round spermatids and in the centrosome region in elongating spermatids. Furthermore, we observed that SEPT12/SPAG4/LAMINB1 formed complexes and were coexpressed in the nuclear periphery of round spermatids. In addition, mutated SEPT12, which was screened from an infertile man, affected the integration of these nuclear envelope complexes through coimmunoprecipitation. This was the first study that suggested that SEPT proteins link to the SUN/LAMIN complexes during the formation of nuclear envelopes and are involved in the development of postmeiotic germ cells.
36 CFR § 1260.46 - How does the Department of Defense process referrals?
Code of Federal Regulations, 2013 CFR
2013-07-01
... National Declassification Center (NDC) § 1260.46 How does the Department of Defense process referrals? (a) The Department of Defense (DOD) established the Joint Referral Center (JRC) to review DOD agencies... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true How does the Department of...
1986-06-01
GUIDE JJ TRIMIS Program Office 5401 Westbard Avenue Bethesda, Maryland 20816 W" V NDC Federal Systems. lnc.._" 1300 Piccard Drive .. -Rockville, Marylcn...Project/Teay iUnft1. DOD A A fri-Service Medical Information Systems Program office 11. Contract(C) orGaw a 5401 Westbard Avenue (C) Bethesda, MD 20816
Sucharov, Carmen C.; Helmke, Steve M.; Langer, Stephen J.; Perryman, M. Benjamin; Bristow, Michael; Leinwand, Leslie
2004-01-01
Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure. PMID:15367688
Minyaev, Mikhail E; Nifant'ev, Ilya E; Tavtorkin, Alexander N; Korchagina, Sof'ya A; Zeynalova, Shadana Sh; Ananyev, Ivan V; Churakov, Andrei V
2017-10-01
The crystal structures of rare-earth diaryl- or dialkylphosphate derivatives are poorly explored. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]chloridotetrakis(methanol-κO)neodymium methanol disolvate, [Nd(C 24 H 34 O 4 P)Cl(CH 4 O) 4 ]·2CH 3 OH, (1), and of the lutetium, [Lu(C 24 H 34 O 4 P)Cl(CH 4 O) 4 ]·2CH 3 OH, (2), and yttrium, [Y(C 24 H 34 O 4 P)Cl(CH 4 O) 4 ]·2CH 3 OH, (3), analogues have been obtained by reactions between lithium bis(2,6-diisopropylphenyl)phosphate and LnCl 3 (H 2 O) 6 (in a 2:1 ratio) in methanol. Compounds (1)-(3) crystallize in the C2/c space group. Their crystal structures are isomorphous. The molecule possesses C 2 symmetry with a twofold crystallographic axis passing through the Ln and Cl atoms. The bis(2,6-diisopropylphenyl)phosphate ligands all display a κ 1 O-monodentate coordination mode. The coordination polyhedron for the metal atom [coordination number (CN) = 7] is a distorted pentagonal bipyramid. Each [Ln{O 2 P(O-2,6- i Pr 2 C 6 H 3 ) 2 } 2 Cl(CH 3 OH) 4 ] molecular unit exhibits two intramolecular O-H...O hydrogen bonds, forming six-membered rings, and two intramolecular O-H...Cl interactions, forming four-membered rings. Intermolecular O-H...O hydrogen bonds connect each unit via four noncoordinating methanol molecules with four other units, forming a two-dimensional hydrogen-bond network. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]tetrakis(methanol-κO)(nitrato-κ 2 O,O')neodymium methanol disolvate, [Nd(C 24 H 34 O 4 P)(NO 3 )(CH 4 O) 4 ]·2CH 3 OH, (4), have been obtained in an analogous manner from NdCl 3 (H 2 O) 6 . Compound (4) also crystalizes in the C2/c space group. Its crystal structure is similar to those of (1)-(3). The κ 2 O,O'-bidentate nitrate anion is disordered over a twofold axis, being located nearly on it. Half of the molecule is crystallographically unique (CN Nd = 8). Unlike (1)-(3), complex (4) exhibits disorder of all three methanol molecules, one isopropyl group of the phosphate ligand and the NO 3 - ligand. The structure of (4) displays intra- and intermolecular O-H...O hydrogen bonds similar to those in (1)-(3). Compounds (1)-(4) represent the first reported mononuclear bis[bis(diaryl/dialkyl)phosphate] rare-earth complexes.
A Survey of Object Oriented Languages in Programming Environments.
1987-06-01
subset of natural languages might be more effective , and make the human-computer interface more friendly. 19 .. .. . . -.. -, " ,. o...and complexty of Ada. He meant that the language contained too many features that made it complicated to use effectively . Much of the complexity comes...by sending messages to a class instance. A small subset of the methods in Smalltalk-80 are not expressed in the !-’ Smalhalk-80 programming language
Code of Federal Regulations, 2011 CFR
2011-04-01
... shall appear and the leading zeros in any segment of the NDC number shall be shown, except that leading... listing. (4)(i) If any change occurs in those product characteristics that clearly distinguish one drug... submit that information to FDA. Such a change includes, but is not limited to, a change in active...
North Korea: Back on the Terrorism List?
2010-06-29
Sweden. North Korea has called the investigation’s conclusion a “fabrication.” Pyongyang Korean Central Broadcasting Station, “DPRK NDC Spokesman’s...trainers to southern Lebanon where they instructed Hezbollah cadre in the development of extensive underground military facilities, including tunnels ...Guard” that one such North Korean-assisted facility in southern Lebanon was a sophisticated, 25-kilometer, underground tunnel with numerous assembly
Code of Federal Regulations, 2010 CFR
2010-04-01
... shall appear and the leading zeros in any segment of the NDC number shall be shown, except that leading... listing. (4)(i) If any change occurs in those product characteristics that clearly distinguish one drug... submit that information to FDA. Such a change includes, but is not limited to, a change in active...
NASA Astrophysics Data System (ADS)
Yan, Li; Liu, Wei; Li, Chuanbi; Wang, Yifei; Ma, Li; Dong, Qinqin
2013-03-01
Two novel compounds constructed from aromatic acid and N-Heterocyclic ligands have been synthesized by hydrothermal reaction: [Cd(mip)(1,8-NDC)(H2O)]2 (1) [mip = 2-(3-methoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, 1,8-NDC = naphthalene-1,8-dicarboxylic acid] and Cd(mip)2(NTC)2 (2) [NTC = nicotinic acid]. Compounds 1 and 2 are characterized by elemental analysis, IR, single crystal X-ray diffraction and thermogravimetric analysis (TGA). Single-crystal X-ray investigation reveals that compounds 1-2 are 0 dimensional (0D) structures, and the existence of hydrogen bonds and π-π interactions lead the 0D to 2D novel framework. Hydrogen bonds and π-π interactions are powerful non-covalent intermolecular interactions for directing supra-molecular architectures. TG analysis shows clear courses of weight loss, which corresponds to the decomposition of different ligands. At room temperature, compound 1 exhibits emission at 449 nm upon excitation at 325 nm, and compound 2 shows a strong emission at 656 nm upon excitation at 350 nm. Fluorescent spectrum displays that compounds 1 and 2 are potential luminescent materials.
Miura, Hiroki; Bon, Volodymyr; Senkovska, Irena; Ehrling, Sebastian; Watanabe, Satoshi; Ohba, Masaaki; Kaskel, Stefan
2017-10-17
Controlled nucleation in a micromixer and further crystal growth were used to synthesize Ni 2 (2,6-ndc) 2 dabco (2,6-ndc - 2,6-naphthalenedicarboxylate, dabco - 1,4-diazabicyclo[2.2.2]octane), also termed DUT-8(Ni) (DUT = Dresden University of Technology), with narrow particle size distribution in a range of a few nm to several μm. The crystal size was found to significantly affect the switching characteristics, in particular the gate opening pressure in nitrogen adsorption isotherms at 77 K for this highly porous and flexible network. Below a critical size of about 500 nm, a type Ia isotherm typical of rigid MOFs is observed, while above approximately 1000 nm a pronounced gating behaviour is detected, starting at p/p 0 = 0.2. With increasing crystal size this transition gate becomes steeper indicating a more uniform distribution of activation energies within the crystal ensemble. At an intermediate size (500-1000 nm), the DUT-8(Ni) crystals close during activation but cannot be reopened by nitrogen at 77 K possibly indicating monodomain switching.
Sequence Complexity of Amyloidogenic Regions in Intrinsically Disordered Human Proteins
Das, Swagata; Pal, Uttam; Das, Supriya; Bagga, Khyati; Roy, Anupam; Mrigwani, Arpita; Maiti, Nakul C.
2014-01-01
An amyloidogenic region (AR) in a protein sequence plays a significant role in protein aggregation and amyloid formation. We have investigated the sequence complexity of AR that is present in intrinsically disordered human proteins. More than 80% human proteins in the disordered protein databases (DisProt+IDEAL) contained one or more ARs. With decrease of protein disorder, AR content in the protein sequence was decreased. A probability density distribution analysis and discrete analysis of AR sequences showed that ∼8% residue in a protein sequence was in AR and the region was in average 8 residues long. The residues in the AR were high in sequence complexity and it seldom overlapped with low complexity regions (LCR), which was largely abundant in disorder proteins. The sequences in the AR showed mixed conformational adaptability towards α-helix, β-sheet/strand and coil conformations. PMID:24594841
Hountondji, Codjo; Bulygin, Konstantin; Créchet, Jean-Bernard; Woisard, Anne; Tuffery, Pierre; Nakayama, Jun-Ichi; Frolova, Ludmila; Nierhaus, Knud H; Karpova, Galina; Baouz, Soria
2014-01-01
We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. Here we report the following: (i) We modeled RPL36AL into the structure of the archaeal ortholog RPL44E extracted from the known X-ray structure of the 50S subunit of Haloarcula marismortui. Superimposing the obtained RPL36AL structure with that of P/E tRNA observed in eukaryotic 80S ribosomes suggested that RPL36AL might in addition to its CCA neighbourhood interact with the inner site of the tRNA elbow similar to an interaction pattern known from tRNA•synthetase pairs. (ii) Accordingly, we detected that the isolated recombinant protein RPL36AL can form a tight binary complex with deacylated tRNA, and even tRNA fragments truncated at their CCA end showed a high affinity in the nanomolar range supporting a strong interaction outside the CCA end. (iii) We constructed programmed 80S complexes containing the termination factor eRF1 (stop codon UAA at the A-site) and a 2',3'-dialdehyde tRNA (tRNAox) analog at the P-site. Surprisingly, we observed a crosslinked ternary complex containing the tRNA, eRF1 and RPL36AL crosslinked both to the aldehyde groups of tRNAox at the 2'- and 3'-positions of the ultimate A. We also demonstrated that, upon binding to the ribosomal A-site, eRF1 induces an alternative conformation of the ribosome and/or the tRNA, leading to a novel crosslink of tRNAox to another large-subunit ribosomal protein (namely L37) rather than to RPL36AL, both ribosomal proteins being labeled in a mutually exclusive fashion. Since the human 80S ribosome in complex with P-site bound tRNAox and A-site bound eRF1 corresponds to the post-termination state of the ribosome, the results represent the first biochemical evidence for the positioning of the CCA-arm of the P-tRNA in close proximity to both RPL36AL and eRF1 at the end of the translation process.
Inclusive Political Settlements: New Insights from Yemen’s National Dialogue
2016-03-01
1990s, negotiated settlements have become important vehicles to renegotiate the social contract of countries. More recently, negotiation processes...inclusive negotiation format, involving large segments of civil society, politicians, and experts, and are usually convened in order to negotiate major...practice of inclusive negotiations . We then describe briefly the context and process of the Yemeni National Dialogue Conference (NDC), including the
2000-06-23
conductivity ( NDC ) effects in double barrier resonant tunneling structures (DBRTS) prove the extremely fast frequency response of charge transport (less...UNCLASSIFIED Defense Technical Information Center Compilation Part Notice ADP013131 TITLE: Multiple-Barrier Resonant Tunneling Structures for...Institute Multiple-barrier resonant tunneling structures for application in a microwave generator stabilized by microstrip resonator S. V. Evstigneev, A. L
2013-06-01
with an EHR .................................................. 97 C. SWOT ANALYSIS OF USING QR CODES WITH THE NDC AND WITH EHRS...96 Figure 41. SWOT analysis ................................................................................... 99 xiii LIST OF...Coordinator for Health Information Technology OTC Over-the-Counter PHI Personal Health Information QR Quick Response SWOT Strengths, Weaknesses
Roher, Alex E; Maarouf, Chera L; Malek-Ahmadi, Michael; Wilson, Jeffrey; Kokjohn, Tyler A; Daugs, Ian D; Whiteside, Charisse M; Kalback, Walter M; Macias, MiMi P; Jacobson, Sandra A; Sabbagh, Marwan N; Ghetti, Bernardino; Beach, Thomas G
2013-01-01
Alzheimer’s disease (AD) dementia impacts all facets of higher order cognitive function and is characterized by the presence of distinctive pathological lesions in the gray matter (GM). The profound alterations in GM structure and function have fostered the view that AD impacts are primarily a consequence of GM damage. However, the white matter (WM) represents about 50% of the cerebrum and this area of the brain is substantially atrophied and profoundly abnormal in both sporadic AD (SAD) and familial AD (FAD). We examined the WM biochemistry by ELISA and Western blot analyses of key proteins in 10 FAD cases harboring mutations in the presenilin genes PSEN1 and PSEN2 as well as in 4 non-demented control (NDC) individuals and 4 subjects with SAD. The molecules examined were direct substrates of PSEN1 such as Notch-1 and amyloid precursor protein (APP). In addition, apolipoproteins, axonal transport molecules, cytoskeletal and structural proteins, neurotrophic factors and synaptic proteins were examined. PSEN-FAD subjects had, on average, higher amounts of WM amyloid-beta (Aβ) peptides compared to SAD, which may play a role in the devastating dysfunction of the brain. However, the PSEN-FAD mutations we examined did not produce uniform increases in the relative proportions of Aβ42 and exhibited substantial variability in total Aβ levels. These observations suggest that neurodegeneration and dementia do not depend solely on enhanced Aβ42 levels. Our data revealed additional complexities in PSEN-FAD individuals. Some direct substrates of γ-secretase, such as Notch, N-cadherin, Erb-B4 and APP, deviated substantially from the NDC group baseline for some, but not all, mutation types. Proteins that were not direct γ-secretase substrates, but play key structural and functional roles in the WM, likewise exhibited varied concentrations in the distinct PSEN mutation backgrounds. Detailing the diverse biochemical pathology spectrum of PSEN mutations may offer valuable insights into dementia progression and the design of effective therapeutic interventions for both SAD and FAD. PMID:24093083
NASA Astrophysics Data System (ADS)
Zhang, Fan; Lin, Qiu-Yue; Hu, Wan-Li; Song, Wen-Ji; Shen, Shu-Ting; Gui, Pan
2013-06-01
Three new transition metal complexes [Mn2(DCA)2(bipy)2]·5H2O (1), [M2(DCA)2(bipy)2(H2O)]·10H2O(M = Ni(II)(2);Zn(II)(3)), (DCA = demethylcantharate, 7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C8H8O5) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and X-ray diffraction techniques. Each metal ion was six-coordinated in complexes. Complex 1 has a Mn2O2 center. Complexes 2 and 3 have asymmetric binuclear structure. Great amount of intermolecular hydrogen-bonding and π-π* stacking interactions were formed in these complex structures. The DNA-binding properties of complexes were investigated by electronic absorption spectra and viscosity measurements. The DNA binding constants Kb/(L mol-1) were 1.71 × 104 (1), 2.62 × 104 (2) and 1.59 × 104 (3) at 298 K. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) strongly through static quenching. The protein binding constants Ka/(L mol-1) were 7.27 × 104 (1), 4.55 × 104 (2) and 7.87 × 104 L mol-1 (3) and binding site was one. The complexes bind more tightly with DNA and BSA than with ligands. Complexes 1 and 3 had stronger inhibition ratios than Na2(DCA) against human hepatoma cells (SMMC-7721) lines and human gastric cancer cells (MGC80-3) lines in vitro. Complex 3 showed the strongest antiproliferative activity against SMMC-7721 (IC50 = 29.46 ± 2.12 μmol L-1) and MGC80-3 (IC50 = 27.02 ± 2.38 μmol L-1), which shows potential in anti-cancer drug development.
Raju, Murugesan; Mooney, Brian P.; Thakkar, Kavi M.; Giblin, Frank J.; Schey, Kevin L.; Sharma, K. Krishna
2015-01-01
Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide–mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways. PMID:25639202
Raju, Murugesan; Mooney, Brian P; Thakkar, Kavi M; Giblin, Frank J; Schey, Kevin L; Sharma, K Krishna
2015-03-01
Earlier we reported that low molecular weight (LMW) peptides accumulate in aging human lens tissue and that among the LMW peptides, the chaperone inhibitor peptide αA66-80, derived from α-crystallin protein, is one of the predominant peptides. We showed that in vitro αA66-80 induces protein aggregation. The current study was undertaken to determine whether LMW peptides are also present in guinea pig lens tissue subjected to hyperbaric oxygen (HBO) in vivo. The nuclear opacity induced by HBO in guinea pig lens is the closest animal model for studying age-related cataract formation in humans. A LMW peptide profile by mass spectrometry showed the presence of an increased amount of LMW peptides in HBO-treated guinea pig lenses compared to age-matched controls. Interestingly, the mass spectrometric data also showed that the chaperone inhibitor peptide αA66-80 accumulates in HBO-treated guinea pig lens. Following incubation of synthetic chaperone inhibitor peptide αA66-80 with α-crystallin from guinea pig lens extracts, we observed a decreased ability of α-crystallin to inhibit the amorphous aggregation of the target protein alcohol dehydrogenase and the formation of large light scattering aggregates, similar to those we have observed with human α-crystallin and αA66-80 peptide. Further, time-lapse recordings showed that a preformed complex of α-crystallin and αA66-80 attracted additional crystallin molecules to form even larger aggregates. These results demonstrate that LMW peptide-mediated cataract development in aged human lens and in HBO-induced lens opacity in the guinea pig may have common molecular pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.
US NDC Modernization: Service Oriented Architecture Study Status
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hamlet, Benjamin R.; Encarnacao, Andre Villanova; Harris, James M.
2014-12-01
This report is a progress update on the USNDC Modernization Service Oriented Architecture (SOA) study describing results from Inception Iteration 1, which occurred between October 2012 and March 2013. The goals during this phase are 1) discovering components of the system that have potential service implementations, 2) identifying applicable SOA patterns for data access, service interfaces, and service orchestration/choreography, and 3) understanding performance tradeoffs for various SOA patterns
Southeast Asia Report, No. 1357
1983-10-21
observations as a working journalist. The rah-rah boys in one corner were in high spirit. The inquisition got to a point where a former woman...Business Club held that so-called dialogue, working newspapermen themselves have been discussing their predicament and have come up with some...Interbank is still being worked out. The foreign bank, Ongpin said, wants to get into Interbank even before its’ takeover by NDC. Ongpin
Summaries of Research - Fiscal Year 1991.
1992-05-01
determine the cost effectiveness of Navy dental technicians applying occlusal sealants to teeth with incipient caries has been completed at NDC, San Diego... Water and Sodium Ion Concentration on the rate of Crack Propagation and Transverse Strength in Dental Porcelains" has been submitted for publication. An...MARYLAND A long term study to evaluate release kinetics of fluoride from various composite materials was begun. To date, ten different materials have
2013-11-14
Rica, Ecuador , El Salvador, Guatemala, Guyana, Haiti, Honduras, Jamaica, Nicaragua, Panama, Paraguay, Peru, Saint Lucia (American Red Cross, n.d.c) 3...contribute to society. (Children International, n.d.a) Currently or previously involved in SOUTHCOM: Honduras, Ecuador , Guatemala, Chile, Honduras...Republic, El Salvador, Guatemala, Guyana, Haiti, Honduras, Jamaica, Nicaragua, Columbia, Ecuador , Bolivia, Brazil, Peru, Paraguay, Chile, and Argentina
Zeglam, Adel M; Al-Ogab, Marwa F; Al-Shaftery, Thouraya
2015-09-01
To evaluate the routine usage of Magnetic Resonance Imaging (MRI) of brain and estimate the prevalence of brain abnormalities in children presenting to the Neurodevelopment Clinic of Al-Khadra Hospital (NDC-KH), Tripoli, Libya with autistic spectrum disorders (ASD). The records of all children with ASD presented to NDC-KH over 4-year period (from January 2009 to December 2012) were reviewed. All MRIs were acquired with a 1.5-T Philips (3-D T1, T2, FLAIR coronal and axial sequences). MRIs were reported to be normal, abnormal or no significant abnormalities by a consultant neuroradiologist. One thousand and seventy-five children were included in the study. Seven hundred and eighty-two children (72.7 %) had an MRI brain of whom 555 (71 %) were boys. 26 children (24 males and 2 females) (3.3 %) demonstrated MRI abnormalities (8 leukodystrophic changes, 4 periventricular leukomalacia, 3 brain atrophy, 2 tuberous sclerosis, 2 vascular changes, 1 pineoblastoma, 1 cerebellar angioma, 1 cerebellar hypoplasia, 3 agenesis of corpus callosum, 1 neuro-epithelial cyst). An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in children with autism. These results could contribute to further research into the pathogenesis of autistic spectrum disorder.
Understanding the origin of Paris Agreement emission uncertainties
NASA Astrophysics Data System (ADS)
Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J. J.; Riahi, Keywan
2017-06-01
The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO2e yr-1. We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harris, James M.; Prescott, Ryan; Dawson, Jericah M.
2014-11-01
Sandia National Laboratories has prepared a ROM cost estimate for budgetary planning for the IDC Reengineering Phase 2 & 3 effort, based on leveraging a fully funded, Sandia executed NDC Modernization project. This report provides the ROM cost estimate and describes the methodology, assumptions, and cost model details used to create the ROM cost estimate. ROM Cost Estimate Disclaimer Contained herein is a Rough Order of Magnitude (ROM) cost estimate that has been provided to enable initial planning for this proposed project. This ROM cost estimate is submitted to facilitate informal discussions in relation to this project and is NOTmore » intended to commit Sandia National Laboratories (Sandia) or its resources. Furthermore, as a Federally Funded Research and Development Center (FFRDC), Sandia must be compliant with the Anti-Deficiency Act and operate on a full-cost recovery basis. Therefore, while Sandia, in conjunction with the Sponsor, will use best judgment to execute work and to address the highest risks and most important issues in order to effectively manage within cost constraints, this ROM estimate and any subsequent approved cost estimates are on a 'full-cost recovery' basis. Thus, work can neither commence nor continue unless adequate funding has been accepted and certified by DOE.« less
Vatansever, Fatma; Hamblin, Michael R.
2016-01-01
Core–shell CdSe/ZnS quantum dots (QDs) are useful as tunable photostable fluorophores for multiple applications in industry, biology, and medicine. However, to achieve the optimum optical properties, the surface of the QDs must be passivated to remove charged sites that might bind extraneous substances and allow aggregation. Here we describe a method of growing an organic polymer corona onto the QD surface using the bottom-up approach of surface-initiated ring-opening metathesis polymerization (SI-ROMP) with Grubbs catalyst. CdSe/ZnS QDs were first coated with mercaptopropionic acid by displacing the original trioctylphosphine oxide layer, and then reacted with 7-octenyl dimethyl chlorosilane. The resulting octenyl double bonds allowed the attachment of ruthenium alkylidene groups as a catalyst. A subsequent metathesis reaction with strained bicyclic monomers (norbornene-dicarbonyl chloride (NDC), and a mixture of NDC and norbornenylethylisobutyl-polyhedral oligomeric silsesquioxane (norbornoPOSS)) allowed the construction of tethered organic homo-polymer or co-polymer layers onto the QD. Compounds were characterized by FT-IR, 1H-NMR, X-ray photoelectron spectroscopy, differential scanning calorimetry, and transmission electron microscopy. Atomic force microscopy showed that the coated QDs were separate and non-aggregated with a range of diameter of 48–53 nm. PMID:28360819
DOE Office of Scientific and Technical Information (OSTI.GOV)
McIntyre, Justin I.; Schrom, Brian T.; Cooper, Matthew W.
2016-03-08
Abstract Several hundred simulated radioxenon beta-gamma data files were developed to assist in evaluating the performance and results from radioxenon concentration calculation analysis at the International Data Center (IDC) and other National Data Centers (NDC). PNNL developed a Beta-Gamma Simulator (BGSim) that incorporated GEANT-modeled data sets from radioxenon decay chains, as well as functionality to use nuclear detector-acquired data sets to create new beta-gamma spectra with varying amounts of background, 133Xe, 131mXe, 133mXe, 135Xe, and 222Rn and its decay products. The program has been implemented on a web-based applications platform and allows the user to create very specific data setsmore » that incorporate most of the operational parameters for the current beta-gamma systems deployed in the International Monitoring System (IMS) and the On-site Inspection (OSI) equipment. After an initial beta-gamma simulations program was developed, additional uses began to be identified for the program output: training sets of two-dimensional spectra for data analysts at the IDC and other NDC, spectra for exercises such as the Integrated Field Exercise 2014 (IFE14) held in Jordan at the Dead Sea, and testing new analysis methods and algorithms« less
Understanding the origin of Paris Agreement emission uncertainties
Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J. J.; Riahi, Keywan
2017-01-01
The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO2e yr−1. We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time. PMID:28585924
Understanding the origin of Paris Agreement emission uncertainties.
Rogelj, Joeri; Fricko, Oliver; Meinshausen, Malte; Krey, Volker; Zilliacus, Johanna J J; Riahi, Keywan
2017-06-06
The UN Paris Agreement puts in place a legally binding mechanism to increase mitigation action over time. Countries put forward pledges called nationally determined contributions (NDC) whose impact is assessed in global stocktaking exercises. Subsequently, actions can then be strengthened in light of the Paris climate objective: limiting global mean temperature increase to well below 2 °C and pursuing efforts to limit it further to 1.5 °C. However, pledged actions are currently described ambiguously and this complicates the global stocktaking exercise. Here, we systematically explore possible interpretations of NDC assumptions, and show that this results in estimated emissions for 2030 ranging from 47 to 63 GtCO 2 e yr -1 . We show that this uncertainty has critical implications for the feasibility and cost to limit warming well below 2 °C and further to 1.5 °C. Countries are currently working towards clarifying the modalities of future NDCs. We identify salient avenues to reduce the overall uncertainty by about 10 percentage points through simple, technical clarifications regarding energy accounting rules. Remaining uncertainties depend to a large extent on politically valid choices about how NDCs are expressed, and therefore raise the importance of a thorough and robust process that keeps track of where emissions are heading over time.
MODELING ACUTE EXPOSURE TO SOLAR RADIATION
One of the major technical challenges in calculating solar flux on the human form has been the complexity of the surface geometry (i.e., the surface normal vis a vis the incident radiation). The American Cancer Society reports that over 80% of skin cancers occur on the face, he...
Hountondji, Codjo; Bulygin, Konstantin; Créchet, Jean-Bernard; Woisard, Anne; Tuffery, Pierre; Nakayama, Jun-ichi; Frolova, Ludmila; Nierhaus, Knud H; Karpova, Galina; Baouz, Soria
2014-01-01
We have demonstrated previously that the E-site specific protein RPL36AL present in human ribosomes can be crosslinked with the CCA-end of a P-tRNA in situ. Here we report the following: (i) We modeled RPL36AL into the structure of the archaeal ortholog RPL44E extracted from the known X-ray structure of the 50S subunit of Haloarcula marismortui. Superimposing the obtained RPL36AL structure with that of P/E tRNA observed in eukaryotic 80S ribosomes suggested that RPL36AL might in addition to its CCA neighbourhood interact with the inner site of the tRNA elbow similar to an interaction pattern known from tRNA•synthetase pairs. (ii) Accordingly, we detected that the isolated recombinant protein RPL36AL can form a tight binary complex with deacylated tRNA, and even tRNA fragments truncated at their CCA end showed a high affinity in the nanomolar range supporting a strong interaction outside the CCA end. (iii) We constructed programmed 80S complexes containing the termination factor eRF1 (stop codon UAA at the A-site) and a 2’,3’-dialdehyde tRNA (tRNAox) analog at the P-site. Surprisingly, we observed a crosslinked ternary complex containing the tRNA, eRF1 and RPL36AL crosslinked both to the aldehyde groups of tRNAox at the 2’- and 3’-positions of the ultimate A. We also demonstrated that, upon binding to the ribosomal A-site, eRF1 induces an alternative conformation of the ribosome and/or the tRNA, leading to a novel crosslink of tRNAox to another large-subunit ribosomal protein (namely L37) rather than to RPL36AL, both ribosomal proteins being labeled in a mutually exclusive fashion. Since the human 80S ribosome in complex with P-site bound tRNAox and A-site bound eRF1 corresponds to the post-termination state of the ribosome, the results represent the first biochemical evidence for the positioning of the CCA-arm of the P-tRNA in close proximity to both RPL36AL and eRF1 at the end of the translation process. PMID:25191528
Purification, characterization and crystallization of the human 80S ribosome
Khatter, Heena; Myasnikov, Alexander G.; Mastio, Leslie; Billas, Isabelle M. L.; Birck, Catherine; Stella, Stefano; Klaholz, Bruno P.
2014-01-01
Ribosomes are key macromolecular protein synthesis machineries in the cell. Human ribosomes have so far not been studied to atomic resolution because of their particularly complex structure as compared with other eukaryotic or prokaryotic ribosomes, and they are difficult to prepare to high homogeneity, which is a key requisite for high-resolution structural work. We established a purification protocol for human 80S ribosomes isolated from HeLa cells that allows obtaining large quantities of homogenous samples as characterized by biophysical methods using analytical ultracentrifugation and multiangle laser light scattering. Samples prepared under different conditions were characterized by direct single particle imaging using cryo electron microscopy, which helped optimizing the preparation protocol. From a small data set, a 3D reconstruction at subnanometric resolution was obtained showing all prominent structural features of the human ribosome, and revealing a salt concentration dependence of the presence of the exit site tRNA, which we show is critical for obtaining crystals. With these well-characterized samples first human 80S ribosome crystals were obtained from several crystallization conditions in capillaries and sitting drops, which diffract to 26 Å resolution at cryo temperatures and for which the crystallographic parameters were determined, paving the way for future high-resolution work. PMID:24452798
MODELING THE ANATOMICAL DISTRIBUTION OF SUNLIGHT
One of the major technical challenges in calculating solar irradiance on the human form has been the complexity of the surface geometry (i.e. the surface normal vis a vis the incident radiation. Over 80 percent of skin cancers occur on the face, head, and back of the hands. The...
North Korea after Kim Chong-il: Leadership Dynamics and Potential Crisis Scenarios
2011-11-01
legal responsibility, and with specified procedures , the actual process is different.3 To date, regime dynamics in the Kim Chong-il era have been... procedures and regulations provide the outlines of formal rule, the 3 For a detailed examination of how...was also made an alternate member. It is also worth noting that 10 of the 12 members of the NDC were represented in the new Politburo lineup , thus
Structural and Electrical-Optical Characterizations of Semiconductor-Atomic Superlattice
2007-05-01
and Avalanche diodes certainly fall into this category. Resonant tunneling diodes like Esaki Tunnel diodes are NDC devices belong to a class where...Heterostructures, Eds. M. Dutta and M. Stroscio, (World Sci. 2003, Singapore), p221 177 Cooling by Inverse Nottingham Effect with Resonant Tunneling ...controlled emitter, V. Semet, V.T. Binh, J.Zhang, J.Yang, M.A. Khan, and R. Tsu, APL. 84,1937 (2004) 186 Stability Issues in Tunneling via Quantum
On-Chip Timing of Solid State QUBITS
2002-11-13
NDC is well pronounced – with the increase of some 100 mT the gap is considerably quenched and single electron tunneling re-emerges. Apparently we...quantum dots contain roughly 10 - 100 electrons and are attached to metallic leads by tunneling barriers. The main advantage of heterostructures is the...blockade of transport at the peak marked B. The resonances left and right indicate single electron tunneling (A) and a quantum dot state with a
DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, Eun-Jung; Hur, Shin-Kyoung; Lee, Han-Sae
2011-12-16
Highlights: Black-Right-Pointing-Pointer The N-terminal domain of hIno80 is important for binding to the spindle. Black-Right-Pointing-Pointer The hIno80 N-terminal domain binds to tubulin and microtubule in vitro. Black-Right-Pointing-Pointer The E-hook of tubulin is critical for hIno80 binding to tubulin and microtubule. Black-Right-Pointing-Pointer Tip49a does not bind to microtubule and dispensable for spindle formation. -- Abstract: The human INO80 chromatin remodeling complex, comprising the Ino80 ATPase (hIno80) and the associated proteins such as Tip49a, has been implicated in a variety of nuclear processes other than transcription. We previously have found that hIno80 interacts with tubulin and co-localizes with the mitotic spindle andmore » is required for spindle formation. To better understand the role of hIno80 in spindle formation, we further investigated the interaction between hIno80 and microtubule. Here, we show that the N-terminal domain, dispensable for the nucleosome remodeling activity, is important for hIno80 to interact with tubulin and co-localize with the spindle. The hIno80 N-terminal domain binds to monomeric tubulin and polymerized microtubule in vitro, and the E-hook of tubulin, involved in the polymerization of microtubule, is critical for this binding. Tip49a, which has been reported to associate with the spindle, does not bind to microtubule in vitro and dispensable for spindle formation in vivo. These results suggest that hIno80 can play a direct role in the spindle assembly independent of its chromatin remodeling activity.« less
40 CFR 80.49 - Fuels to be used in augmenting the complex emission model through vehicle testing.
Code of Federal Regulations, 2014 CFR
2014-07-01
... complex emission model through vehicle testing. 80.49 Section 80.49 Protection of Environment... Reformulated Gasoline § 80.49 Fuels to be used in augmenting the complex emission model through vehicle testing... augmenting the complex emission model with a parameter not currently included in the complex emission model...
40 CFR 80.49 - Fuels to be used in augmenting the complex emission model through vehicle testing.
Code of Federal Regulations, 2013 CFR
2013-07-01
... complex emission model through vehicle testing. 80.49 Section 80.49 Protection of Environment... Reformulated Gasoline § 80.49 Fuels to be used in augmenting the complex emission model through vehicle testing... augmenting the complex emission model with a parameter not currently included in the complex emission model...
40 CFR 80.49 - Fuels to be used in augmenting the complex emission model through vehicle testing.
Code of Federal Regulations, 2011 CFR
2011-07-01
... complex emission model through vehicle testing. 80.49 Section 80.49 Protection of Environment... Reformulated Gasoline § 80.49 Fuels to be used in augmenting the complex emission model through vehicle testing... augmenting the complex emission model with a parameter not currently included in the complex emission model...
40 CFR 80.49 - Fuels to be used in augmenting the complex emission model through vehicle testing.
Code of Federal Regulations, 2012 CFR
2012-07-01
... complex emission model through vehicle testing. 80.49 Section 80.49 Protection of Environment... Reformulated Gasoline § 80.49 Fuels to be used in augmenting the complex emission model through vehicle testing... augmenting the complex emission model with a parameter not currently included in the complex emission model...
1981-01-31
quantities for h i ;.;h-:t It i 1 ndc hurst s 1BMI.I Determines t ime-independent fireball quantities for low-altitude bursts 10 Table 1...of reference Oval of Cassini (km) LAFBP - vortex longitudinal radius (km) LAFBP - vortex transverse radius (km) Power law exponent Inner scale...Maximum slant range of ionization from transmitter (km) Power law exponent Frequency (Hz) Striation velocity flag Propagation path index Radius
Environmental Aspects of Dredging: What About Air Quality?
2009-01-01
District, IL, 61204, PH (309) 794-5735 ext.6108, FAX: (309) 794-5 5712, email: mark.j.anderson@usace.army.mil 6 2Civil & Environmental Engineering Dept...Michigan Tech University , Houghton, MI 7 49931, PH: (906) 487-1981, FAX: (906) 487-2943, email: barkdoll@mtu.edu 8 9 ABSTRACT 10 Dredging has...the U. S. Army Corps of Engineers (USACE) dredged a total of 26 204.2 million cubic yards (CY) of sediment (NDC 2007). Navigation maintenance 27
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hua, Xiu-Ni; Qin, Lan; Yan, Xiao-Zhi
Hydrothermal reactions of N-auxiliary flexible exo-bidentate ligand 1,3-bis(4-pyridyl)propane (bpp) and carboxylates ligands naphthalene-2,6-dicarboxylic acid (2,6-H{sub 2}ndc) or 4,4′-(hydroxymethylene)dibenzoic acid (H{sub 2}hmdb), in the presence of cadmium(II) salts have given rise to two novel metal-organic frameworks based on flexible ligands (FL-MOFs), namely, [Cd{sub 2}(2,6-ndc){sub 2}(bpp)(DMF)]·2DMF (1) and [Cd{sub 3}(hmdb){sub 3}(bpp)]·2DMF·2EtOH (2) (DMF=N,N-Dimethylformamide). Single-crystal X-ray diffraction analyses revealed that compound 1 exhibits a three-dimensional self-penetrating 6-connected framework based on dinuclear cluster second building unit. Compound 2 displays an infinite three-dimensional ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster and V-shaped organic linkers. The flexible bpp ligand displays different conformations inmore » 1 and 2, which are successfully controlled by size-matching mixed ligands during the self-assembly process. - Graphical abstract: Compound 1 exhibits a 3D self-penetrating 6-connected framework based on dinuclear cluster, and 2 displays an infinite 3D ‘Lucky Clover’ shape (2,10)-connected network based on the trinuclear cluster. The flexible 1,3-bis(4-pyridyl)propane ligand displays different conformations in 1 and 2, which successfully controlled by size-matching mixed ligands during the self-assembly process.« less
Crystal structure of the human natural killer cell inhibitory receptor KIR2DL1-HLA-Cw4 complex.
Fan, Q R; Long, E O; Wiley, D C
2001-05-01
Inhibitory natural killer (NK) cell receptors down-regulate the cytotoxicity of NK cells upon recognition of specific class I major histocompatibility complex (MHC) molecules on target cells. We report here the crystal structure of the inhibitory human killer cell immunoglobulin-like receptor 2DL1 (KIR2DL1) bound to its class I MHC ligand, HLA-Cw4. The KIR2DL1-HLA-Cw4 interface exhibits charge and shape complementarity. Specificity is mediated by a pocket in KIR2DL1 that hosts the Lys80 residue of HLA-Cw4. Many residues conserved in HLA-C and in KIR2DL receptors make different interactions in KIR2DL1-HLA-Cw4 and in a previously reported KIR2DL2-HLA-Cw3 complex. A dimeric aggregate of KIR-HLA-C complexes was observed in one KIR2DL1-HLA-Cw4 crystal. Most of the amino acids that differ between human and chimpanzee KIRs with HLA-C specificities form solvent-accessible clusters outside the KIR-HLA interface, which suggests undiscovered interactions by KIRs.
mRNA 3' of the A site bound codon is located close to protein S3 on the human 80S ribosome.
Molotkov, Maxim V; Graifer, Dmitri M; Popugaeva, Elena A; Bulygin, Konstantin N; Meschaninova, Maria I; Ven'yaminova, Aliya G; Karpova, Galina G
2006-07-01
Ribosomal proteins neighboring the mRNA downstream of the codon bound at the decoding site of human 80S ribosomes were identified using three sets of mRNA analogues that contained a UUU triplet at the 5' terminus and a perfluorophenylazide cross-linker at guanosine, adenosine or uridine residues placed at various locations 3' of this triplet. The positions of modified mRNA nucleotides on the ribosome were governed by tRNA(Phe) cognate to the UUU triplet targeted to the P site. Upon mild UV-irradiation, the mRNA analogues cross-linked preferentially to the 40S subunit, to the proteins and to a lesser extent to the 18S rRNA. Cross-linked nucleotides of 18S rRNA were identified previously. In the present study, it is shown that among the proteins the main target for cross-linking with all the mRNA analogues tested was protein S3 (homologous to prokaryotic S3, S3p); minor cross-linking to protein S2 (S5p) was also detected. Both proteins cross-linked to mRNA analogues in the ternary complexes as well as in the binary complexes (without tRNA). In the ternary complexes protein S15 (S19p) also cross-linked, the yield of the cross-link decreased significantly when the modified nucleotide moved from position +5 to position +12 with respect to the first nucleotide of the P site bound codon. In several ternary complexes minor cross-linking to protein S30 was likewise detected. The results of this study indicate that S3 is a key protein at the mRNA binding site neighboring mRNA downstream of the codon at the decoding site in the human ribosome.
Agabou, Amir; Ouchenane, Zouleikha; Ngba Essebe, Christelle; Khemissi, Salim; Chehboub, Mohamed Tedj Eddine; Chehboub, Ilyes Bey; Dunyach-Remy, Catherine
2017-01-01
The spread of toxinogenic Staphylococcus aureus is a public health problem in Africa. The objectives of the study were to investigate the rate of S. aureus nasal carriage and molecular characteristics of these strains in livestock and humans in three Algerian provinces. Nasal samples were collected from camels, horses, cattle, sheep and monkeys, as well as humans in contact with them. S. aureus isolates were genotyped using DNA microarray. The rate of S. aureus nasal carriage varied between species: camels (53%), humans and monkeys (50%), sheep (44.2%), horses (15.2%) and cattle (15%). Nine methicillin-resistant S. aureus (MRSA) isolates (7.6%) were identified, isolated from camels and sheep. The S. aureus isolates belonged to 15 different clonal complexes. Among them, PVL+ (Panton–Valentine Leukocidin) isolates belonging to ST80-MRSA-IV and ST152-MSSA were identified in camels (n = 3, 13%) and sheep (n = 4, 21.1%). A high prevalence of toxinogenic animal strains was noted containing TSST-1- (22.2%), EDINB- (29.6%) and EtD- (11.1%) encoding genes. This study showed the dispersal of the highly human pathogenic clones ST152-MSSA and ST-80-MRSA in animals. It suggests the ability of some clones to cross the species barrier and jump between humans and several animal species. PMID:28946704
Stabilization of a human recombinant factor VIII by poloxamer 188 in relation to polysorbate 80.
Clark, Jakson; Montgomery, Jade; Squires, Ryan; McGuire, Joseph
2016-03-01
Detection of enhanced surface tension depression by surfactant in the presence of protein was recently suggested as a basis for determining whether protein stabilization by that surfactant is owing to surfactant forming a steric barrier at interfaces or surfactant association with the protein. In particular, protein interaction with surfactant aggregates may lead to an increased concentration of monomers thus enhancing surfactant adsorption, or to formation of surfactant-protein complexes having little or no effect on adsorption. We compared the initial rates of surface tension depression by poloxamer 188 and polysorbate 80 (PS 80) in the presence and absence of a human recombinant factor VIII (rFVIII). Indirect evidence had suggested poloxamer 188 enters into stable associations with rFVIII in solution but does not form a steric barrier at the interface, while PS 80 behaves in contrary fashion. In this study, we show the presence of rFVIII caused an increase in the rate (reduction in the activation energy) of PS 80 adsorption, while no such change was recorded in the case of poloxamer 188. Thus, we provide substantiation for detection of protein-mediated acceleration of surfactant adsorption as a means to compare different surfactants in relation to their favored mechanism for protein stabilization.
2012-03-01
PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) CNA Corporation,4825 Mark Center Drive... industry & USMC OMFTS experience Project Team created BPR “activity model” (Oct-Dec 1995) OPNAV N513, N812; HQMC Plans, PP&O; MCCDC; NDC; SRA...Alexandria,VA,22311 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) 11
Applications of Known Quantitative Techniques for Developing Airborne ASW Crew Performance Criteria,
1967-07-01
environmental foot tunnel enable’s accurate tests to be conducted under specifications, controlled conditions, MA Ch I N E ( ‘OMI ’l ’F t T ION SERVICES C...ph~- 51 olo gical nioni tur ing equ ip— cc i dt’ a r t e ’t~ cci C ~~ii ’ ri iue ’nt s can hi’ ~‘onc1ui-ted u ndc r V a t t e s t s nie ’ni ; I
Particle Sizing in a Fuel-Rich Ramjet Combustor.
1983-08-01
Scattering wind tunnel , and for his assistance during the opera- Technique for Particle Sizing Based on Laser tions in the test cell and on other...000 40 0 0 -L .. 00 zzz C00 < 0 0 0 0 *Y -0 000 CL QU 00- V00 c 0 N 0 2 0000 4 008 -- I ~-_______ 00 0z m0 c00 00j i40 06.1 4~ < NDc . o4 i P-0 0 0 4
Force Method Optimization II. Volume II. User’s Manual.
1982-11-01
column labels ICC Iteration counter ICHECK Vector for intermediate output, identifying the convergence status of unknowns, 0 = has not converged, 1...NDC,NW,SIG,ND,IDYN,UP,LOW,IAREA,IMU, ALAMBDW,WARAY,NSN.,NDCNL,NXNL,NWNL,NDNNL, NSENLIRST, ICHECK ,WDYN,PR1,MAXIT,WS,ARAY) 8. Input Tapes: None 9. Output...IMUSL,IMUDL,IAREA, IMU, P,NDN,UP,LOW,IX,IDYN,NW,IMUXL,IMUWL,ICC,ALAMBD, AMIN,WT,KL,NODE,ND,COND, IDEL .NSNL,NDCNL, NXNL, NWNL, ICHECK ,WDYN,PRI,WS,MAXT
NATO Nuclear Reductions and the Assurance of Central and Eastern European Allies
2013-10-01
entirely. 35 Endnotes 1 Ronald D. Asmus and Alexandr Vondra, “The Origins of Atlanticism in Central and Eastern Europe,” Cambridge...pp. 3-6, available at http://www.ndc.nato.int/download/downloads.php?icode=195. 61 Asmus and Vondra, “The Origins of Atlanticism in Central and... Origins of Atlanticism in Central and Eastern Europe,” op. cit., p. 211. 132 Credible Deterrence for NATO in the XXI Century, op. cit, pp. 12-13
Yang, Guang; Liu, Chao; Chen, Shih-Hsun; Kassab, Muzaffer A; Hoff, J Damon; Yu, Xiaochun
2018-01-01
Abstract DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA damage response. However, the earliest stage of DSB sensing remains elusive. Here, we report that PARP1 and the Ku70/80 complex localize to DNA lesions considerably earlier than other DSB sensors. Using super-resolved fluorescent particle tracking, we further examine the relocation kinetics of PARP1 and the Ku70/80 complex to a single DSB, and find that PARP1 and the Ku70/80 complex are recruited to the DSB almost at the same time. Notably, only the Ku70/80 complex occupies the DSB exclusively in the G1 phase; whereas PARP1 competes with the Ku70/80 complex at the DSB in the S/G2 phase. Moreover, in the S/G2 phase, PARP1 removes the Ku70/80 complex through its enzymatic activity, which is further confirmed by in vitro DSB-binding assays. Taken together, our results reveal PARP1 and the Ku70/80 complex as critical DSB sensors, and suggest that PARP1 may function as an important regulator of the Ku70/80 complex at the DSBs in the S/G2 phase. PMID:29447383
New Communitarianism Movements and Complex Utopia
NASA Astrophysics Data System (ADS)
Akdeniz, K. Gediz
Simulation is a rapidly growing field in social sciences. Simulation theories in social sciences are considered to critique social dynamics and societies which are mostly simulated by media, cinema, TV, internet, etc. Recently we (Akdeniz KG, Disorder in complex human system. In: Fritzsch H, Phua KK (eds) Singapore: proceedings of the conference in Honour of Murray Gell-Mann's 80th birthday quantum mechanics, elementary particles, quantum cosmology and complexity. World Scientific Publishing, Hackensack, pp 630-637, 2009) purposed a simulation theory as a critique theory to investigate disordered human behaviors. In this theory, "Disorder-Sensitive Human Behaviors (DSHB) Simulation Theory", chaotic awareness is also considered as a reality principle in simulation world to complete Baudrillard Simulation Theory (Baudrillard J, Simulacra and simulation. University of Michigan Press, Michigan, 1995). We call the emergence of this reality as zuhur which is different than simulacra. More recently we proposed the complex utopia (Akdeniz KG, From Simulacra to Zuhur in Complex Utopia. 11th International Conference of the Utopian Studies Society, Lublin, 2010; Akdeniz KG, The new identities of the physicist: cyborg-physicist and post-physicist. In: Proceedings of the conference of world international conference of technology and education, Beirut, 2010) to critique the complex societies and communities in simulation world. The challenging agents in the complex utopia are both simulacra and zuhur. In this paper we would like to review "What is the complex utopia?" And we shall critique some global events in framework of complex utopia with particular examples in socio-economic and political contexts.
NASA Astrophysics Data System (ADS)
Zhang, Fan; Lin, Qiu-Yue; Li, Shi-Kun; Zhao, Yu-Ling; Wang, Peng-Peng; Chen, Miao-Miao
2012-12-01
Four new transition metal complexes (Habtz)2[M(DCA)2]·6H2O (M = Co(II) (1), Ni(II) (2), Cu(II) (3), Zn(II) (4); DCA = demethylcantharate, 7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, C8H8O5; Habtz = 2-aminobenzothiazole acid, C7H7N2S) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and thermogravimetric analysis. The coordination number of complex was six. The X-ray diffraction analysis indicated that complex 3 crystallized in the triclinic crystal system with P1¯ space group. The DNA-binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra, viscosity measurements. Title complexes could bind to DNA via partial intercalative mode. The Kb of the complexes were 5.33 × 104 (1), 7.04 × 104 (2), 9.91 × 104 (3) and 5.03 × 104 L mol-1 (4). The results of agarose gel electrophoresis showed that Cu(II) complex could cleave pBR322 plasmid DNA via radical-based mechanism. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) through a static quenching with the binding constants Ka of 1.11 × 104 (1), 1.24 × 106 (2), 8.42 × 105 (3) and 1.75 × 104 L mol-1 (4). The complexes had intense antiproliferative activities against human hepatoma cell lines (SMMC7721) and human gastric cancer cells (MGC80-3) lines in vitro. Cu(II) complex had the strongest activity against human gastric cancer cells.
Bock, Jörg; Braun, Katharina
1999-01-01
Auditory filial imprinting in the domestic chicken is accompanied by a dramatic loss of spine synapses in two higher associative forebrain areas, the mediorostral neostriatum/hyperstriatum ventrale (MNH) and the dorsocaudal neostriatum (Ndc). The cellular mechanisms that underlie this learning-induced synaptic reorganization are unclear. We found that local pharmacological blockade of N-methyl-d-aspartate (NMDA) receptors in the MNH, a manipulation that has been shown previously to impair auditory imprinting, suppresses the learning-induced spine reduction in this region. Chicks treated with the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV) during the behavioral training for imprinting (postnatal day 0–2) displayed similar spine frequencies at postnatal day 7 as naive control animals, which, in both groups, were significantly higher than in imprinted animals. Because the average dendritic length did not differ between the experimental groups, the reduced spine frequency can be interpreted as a reduction of the total number of spine synapses per neuron. In the Ndc, which is reciprocally connected with the MNH and not directly influenced by the injected drug, learning-induced spine elimination was partly suppressed. Spine frequencies of the APV-treated, behaviorally trained but nonimprinted animals were higher than in the imprinted animals but lower than in the naive animals. These results provide evidence that NMDA receptor activation is required for the learning-induced selective reduction of spine synapses, which may serve as a mechanism of information storage specific for juvenile emotional learning events. PMID:10051669
Yao, Wei; Beckwith, Sean L.; Zheng, Tina; Young, Thomas; Dinh, Van T.; Ranjan, Anand; Morrison, Ashby J.
2015-01-01
ATP-dependent chromatin remodeling, which repositions and restructures nucleosomes, is essential to all DNA-templated processes. The INO80 chromatin remodeling complex is an evolutionarily conserved complex involved in diverse cellular processes, including transcription, DNA repair, and replication. The functional diversity of the INO80 complex can, in part, be attributed to specialized activities of distinct subunits that compose the complex. Furthermore, structural analyses have identified biochemically discrete subunit modules that assemble along the Ino80 ATPase scaffold. Of particular interest is the Saccharomyces cerevisiae Arp5-Ies6 module located proximal to the Ino80 ATPase and the Rvb1-Rvb2 helicase module needed for INO80-mediated in vitro activity. In this study we demonstrate that the previously uncharacterized Ies2 subunit is required for Arp5-Ies6 association with the catalytic components of the INO80 complex. In addition, Arp5-Ies6 module assembly with the INO80 complex is dependent on distinct conserved domains within Arp5, Ies6, and Ino80, including the spacer region within the Ino80 ATPase domain. Arp5-Ies6 interacts with chromatin via assembly with the INO80 complex, as IES2 and INO80 deletion results in loss of Arp5-Ies6 chromatin association. Interestingly, ectopic addition of the wild-type Arp5-Ies6 module stimulates INO80-mediated ATP hydrolysis and nucleosome sliding in vitro. However, the addition of mutant Arp5 lacking unique insertion domains facilitates ATP hydrolysis in the absence of nucleosome sliding. Collectively, these results define the requirements of Arp5-Ies6 assembly, which are needed to couple ATP hydrolysis to productive nucleosome movement. PMID:26306040
A core hSSB1–INTS complex participates in the DNA damage response
Zhang, Feng; Ma, Teng; Yu, Xiaochun
2013-01-01
Summary Human single-stranded DNA-binding protein 1 (hSSB1) plays an important role in the DNA damage response and the maintenance of genomic stability. It has been shown that the core hSSB1 complex contains hSSB1, INTS3 and C9orf80. Using protein affinity purification, we have identified integrator complex subunit 6 (INTS6) as a major subunit of the core hSSB1 complex. INTS6 forms a stable complex with INTS3 and hSSB1 both in vitro and in vivo. In this complex, INTS6 directly interacts with INTS3. In response to the DNA damage response, along with INTS3 and hSSB1, INTS6 relocates to the DNA damage sites. Moreover, the hSSB1–INTS complex regulates the accumulation of RAD51 and BRCA1 at DNA damage sites and the correlated homologous recombination. PMID:23986477
An innovative model for achieving breast-feeding success in infants with complex surgical anomalies.
Edwards, Taryn M; Spatz, Diane L
2010-01-01
This manuscript describes an innovative nurse-driven continuous quality improvement project. Infants born with congenital surgical anomalies face significant challenges within the newborn period and human milk/breast-feeding may not be viewed as a priority. In many hospitals, nurses refer families to lactation consultants for all breast-feeding assistance and support. The Transition to Breast Pathway was developed on the basis of the evidence-based standards and protocols at The Children's Hospital of Philadelphia. The pathway consists of (1) initiation of pumping and maintenance of milk supply, (2) mouth care with human milk, (3) skin-to-skin care, (4) nonnutritive sucking at the breast, (5) transitioning to at breast feeds. A sample of 80 infants were enrolled in this project. Major results of the project are as follows: (1) mother's average milk supply was approximately 603 mL/d, (2) 71% (57/80) of the infants received mouth care with human milk, (3) 48% (38/80) mother/infant dyads performed skin-to-skin care, (4) 60% (35/58) of mother/infant dyads performed nonnutritive sucking at the breast, (5) 100% (58/58) of mother-infant dyads transitioned to breast prior to discharge. This continuous quality improvement project demonstrates that nurses can and should lead the process of transitioning infants to at breast feeds.
Nuclear Test Depth Determination with Synthetic Modelling: Global Analysis from PNEs to DPRK-2016
NASA Astrophysics Data System (ADS)
Rozhkov, Mikhail; Stachnik, Joshua; Baker, Ben; Epiphansky, Alexey; Bobrov, Dmitry
2016-04-01
Seismic event depth determination is critical for the event screening process at the International Data Center, CTBTO. A thorough determination of the event depth can be conducted mostly through additional special analysis because the IDC's Event Definition Criteria is based, in particular, on depth estimation uncertainties. This causes a large number of events in the Reviewed Event Bulletin to have depth constrained to the surface making the depth screening criterion not applicable. Further it may result in a heavier workload to manually distinguish between subsurface and deeper crustal events. Since the shape of the first few seconds of signal of very shallow events is very sensitive to the depth phases, cross correlation between observed and theoretic seismograms can provide a basis for the event depth estimation, and so an expansion to the screening process. We applied this approach mostly to events at teleseismic and partially regional distances. The approach was found efficient for the seismic event screening process, with certain caveats related mostly to poorly defined source and receiver crustal models which can shift the depth estimate. An adjustable teleseismic attenuation model (t*) for synthetics was used since this characteristic is not known for most of the rays we studied. We studied a wide set of historical records of nuclear explosions, including so called Peaceful Nuclear Explosions (PNE) with presumably known depths, and recent DPRK nuclear tests. The teleseismic synthetic approach is based on the stationary phase approximation with hudson96 program, and the regional modelling was done with the generalized ray technique by Vlastislav Cerveny modified to account for the complex source topography. The software prototype is designed to be used for the Expert Technical Analysis at the IDC. With this, the design effectively reuses the NDC-in-a-Box code and can be comfortably utilized by the NDC users. The package uses Geotool as a front-end for data retrieval and pre-processing. After the event database is compiled, the control is passed to the driver software, running the external processing and plotting toolboxes, which controls the final stage and produces the final result. The modules are mostly Python coded, C-coded (Raysynth3D complex topography regional synthetics) and FORTRAN coded synthetics from the CPS330 software package by Robert Herrmann of Saint Louis University. The extension of this single station depth determination method is under development and uses joint information from all stations participating in processing. It is based on simultaneous depth and moment tensor determination for both short and long period seismic phases. A novel approach recently developed for microseismic event location utilizing only phase waveform information was migrated to a global scale. It should provide faster computation as it does not require intensive synthetic modelling, and might benefit processing noisy signals. A consistent depth estimate for all recent nuclear tests was produced for the vast number of IMS stations (primary and auxiliary) used in processing.
A Cold Temperature Evaluation of the Bonding Adhesives Used for the MUST Inflatable Shelters
1975-04-01
been known as the US Army Natick Laboratories (NLABS), and the US Army Natick Development Center ( NDC ). AMIN 1W 5Th Whit# WIN~ zD DI• ~kti u...section throughout the test period. The arctic climatic chamber is a closed ci;•uit wind tunnel in which the temperature can be lowered, controlled...and maintained at any level down to -54WC (-65°F). The shelter section was too large to fit in the test section of the tunnel . The shelter had to be
Dynamic Response of Ramjet Inlets to Downstream Perturbations.
1983-01-31
NDC -00784 UNCLASSIFIED N98814-8R-C-8481 F/S 26/4 NL EIIIIIIIII-EIIhIIIIIIIIE EllhlhllllhhI *lfl gi IIDi w,. . , 2 9,- * .t .C- 0- . 1-" "L/" wo 1. I...dual-throat model configured as a small supersonic wind tunnel . References to a diffuser in the task statements reflect these initial ideas. However, it...determination of UB requires a wind tunnel test or possibly a free jet experiment with a large jet diameter compared to the model size. 1 5 17 4 4 4~,d
Different virulence of the species of the Pseudallescheria boydii complex.
Gilgado, Fèlix; Cano, Josep; Gené, Josepa; Serena, Carolina; Guarro, Josep
2009-06-01
Pseudallescheria boydii sensu lato is a complex of species involved in severe human infections. We have evaluated, using a murine model, the virulence of 2 strains of each of the most representative species of the complex, i.e., P. boydii sensu stricto, P. minutispora, Scedosporium apiospermum, S. aurantiacum and S. dehoogii. We used two different inocula, i.e., 5 x 10(4) conidia/ml (for immunosuppressed animals) and 1 x 10(6) conidia/ml (for immunocompetent animals), which were administered intravenously. Scedosporium aurantiacum and S. dehoogii were the most virulent species, causing the death of 80% and 70% of the immunocompetent mice, respectively. The remaining species only killed 0-20% of the animals.
Radhakrishnan, Sarvan Kumar; Lees-Miller, Susan P
2017-09-01
Non-homologous end joining (NHEJ) is the major pathway for the repair of ionizing radiation induced DNA double strand breaks (DSBs) in human cells. Critical to NHEJ is the DNA-dependent interaction of the Ku70/80 heterodimer with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the DNA-PK holoenzyme. However, precisely how Ku recruits DNA-PKcs to DSBs ends to enhance its kinase activity has remained enigmatic, with contradictory findings reported in the literature. Here we address the role of the Ku80 C-terminal region (CTR) in the DNA-dependent interaction of Ku70/80 with DNA-PKcs using purified components and defined DNA structures. Our results show that the Ku80 CTR is required for interaction with DNA-PKcs on short segments of blunt ended 25bp dsDNA or 25bp dsDNA with a 15-base poly dA single stranded (ss) DNA extension, but this requirement is less stringent on longer dsDNA molecules (35bp blunt ended dsDNA) or 25bp duplex DNA with either a 15-base poly dT or poly dC ssDNA extension. Moreover, the DNA-PKcs-Ku complex preferentially forms on 25 bp DNA with a poly-pyrimidine ssDNA extension.Our work clarifies the role of the Ku80 CTR and dsDNA ends on the interaction of DNA-PKcs with Ku and provides key information to guide assembly and biology of NHEJ complexes. Copyright © 2017 Elsevier B.V. All rights reserved.
[Protein S3 in the human 80S ribosome adjoins mRNA from 3'-side of the A-site codon].
Molotkov, M V; Graĭfer, D M; Popugaeva, E A; Bulygin, K N; Meshchaninova, M I; Ven'iaminova, A G; Karpova, G G
2007-01-01
The protein environment of mRNA 3' of the A-site codon (the decoding site) in the human 80S ribosome was studied using a set of oligoribonucleotide derivatives bearing a UUU triplet at the 5'-end and a perfluoroarylazide group at one of the nucleotide residues at the 3'-end of this triplet. Analogues of mRNA were phased into the ribosome using binding at the tRNAPhe P-site, which recognizes the UUU codon. Mild UV irradiation of ribosome complexes with tRNAPhe and mRNA analogues resulted in the predominant crosslinking of the analogues with the 40S subunit components, mainly with proteins and, to a lesser extent, with rRNA. Among the 40S subunit ribosomal proteins, the S3 protein was the main target for modification in all cases. In addition, minor crosslinking with the S2 protein was observed. The crosslinking with the S3 and S2 proteins occurred both in triple complexes and in the absence of tRNA. Within triple complexes, crosslinking with S15 protein was also found, its efficiency considerably falling when the modified nucleotide was moved from positions +5 to +12 relative to the first codon nucleotide in the P-site. In some cases, crosslinking with the S30 protein was observed, it was most efficient for the derivative containing a photoreactive group at the +7 adenosine residue. The results indicate that the S3 protein in the human ribosome plays a key role in the formation of the mRNA binding site 3' of the codon in the decoding site.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K.
DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). But, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcsmore » (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Our collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.« less
Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K.; ...
2016-11-14
DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). But, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcsmore » (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Our collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.« less
The BioPlex Network: A Systematic Exploration of the Human Interactome.
Huttlin, Edward L; Ting, Lily; Bruckner, Raphael J; Gebreab, Fana; Gygi, Melanie P; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E; De Camilli, Pietro; Paulo, Joao A; Harper, J Wade; Gygi, Steven P
2015-07-16
Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80%-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally related proteins. Finally, BioPlex, in combination with other approaches, can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial amyotrophic lateral sclerosis perturb a defined community of interactors. Copyright © 2015 Elsevier Inc. All rights reserved.
The BioPlex Network: A Systematic Exploration of the Human Interactome
Huttlin, Edward L.; Ting, Lily; Bruckner, Raphael J.; Gebreab, Fana; Gygi, Melanie P.; Szpyt, John; Tam, Stanley; Zarraga, Gabriela; Colby, Greg; Baltier, Kurt; Dong, Rui; Guarani, Virginia; Vaites, Laura Pontano; Ordureau, Alban; Rad, Ramin; Erickson, Brian K.; Wühr, Martin; Chick, Joel; Zhai, Bo; Kolippakkam, Deepak; Mintseris, Julian; Obar, Robert A.; Harris, Tim; Artavanis-Tsakonas, Spyros; Sowa, Mathew E.; DeCamilli, Pietro; Paulo, Joao A.; Harper, J. Wade; Gygi, Steven P.
2015-01-01
SUMMARY Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally-related proteins. Finally, BioPlex, in combination with other approaches can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial Amyotrophic Lateral Sclerosis perturb a defined community of interactors. PMID:26186194
Cinnamic Acid Is Partially Involved in Propolis Immunomodulatory Action on Human Monocytes
Conti, Bruno José; Búfalo, Michelle Cristiane; Golim, Marjorie de Assis; Sforcin, José Maurício
2013-01-01
Propolis is a beehive product used in traditional medicine due to its biological properties. It shows a complex chemical composition including phenolics, such as cinnamic acid (Ci). The mechanisms of action of propolis have been the subject of research recently; however, the involvement of Ci on propolis activity was not investigated on immune cells. Ci effects were evaluated on human monocytes, assessing the expression of Toll-like receptors (TLRs), HLA-DR, and CD80. Cytokine production (TNF-α and IL-10) and the fungicidal activity of monocytes were evaluated as well. Data showed that Ci downregulated TLR-2, HLA-DR, and CD80 and upregulated TLR-4 expression by human monocytes. High concentrations of Ci inhibited both TNF-α and IL-10 production, whereas the same concentrations induced a higher fungicidal activity against Candida albicans. TNF-α and IL-10 production was decreased by blocking TLR-4, while the fungicidal activity of monocytes was not affected by blocking TLRs. These results suggest that Ci modulated antigen receptors, cytokine production, and the fungicidal activity of human monocytes depending on concentration, and TLR-4 may be involved in its mechanism of action. Ci seemed to be partially involved in propolis activities. PMID:23762102
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhang, Ju-Wen; Gong, Chun-Hua; Hou, Li-Li
2013-09-15
Three new metal-organic coordination polymers [Co(4-bbc){sub 2}(bbbm)] (1), [Co(3,5-pdc)(bbbm)]·2H{sub 2}O (2) and [Co(1,4-ndc)(bbbm)] (3) (4-Hbbc=4-bromobenzoic acid, 3,5-H{sub 2}pdc=3,5-pyridinedicarboxylic acid, 1,4-H{sub 2}ndc=1,4-naphthalenedicarboxylic acid and bbbm=1,1-(1,4-butanediyl)bis-1H-benzimidazole) were hydrothermally synthesized and structurally characterized. Polymer 1 is a 1D chain formed by the bbbm ligands and Co{sup II} ions. Polymer 2 exhibits a 2D network with a (3·4·5)(3{sup 2}·4·5·6{sup 2}·7{sup 4}) topology. Polymer 3 possesses a 3D three-fold interpenetrating framework. The versatile structures of title polymers indicate that the aromatic carboxylates have an important influence on the dimensionality of 1–3. Moreover, the thermal stability, electrochemical and luminescent properties of 1–3 were investigated. - graphicalmore » abstract: Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were hydrothermally synthesized and structurally characterized. The aromatic carboxylates play a key role in the dimensionality of three polymers. The electrochemical and luminescent properties of three polymers were investigated. Display Omitted - Highlights: • Three bis(benzimidazole)-based cobalt(II) coordination polymers tuned by aromatic carboxylates were obtained. • The aromatic carboxylates have an important influence on the dimensionality of three polymers. • The electrochemical and luminescent properties of three polymers were investigated.« less
Ghosh, Chiranjit; Banik, Gourab D.; Maity, Abhijit; Som, Suman; Chakraborty, Arpita; Selvan, Chitra; Ghosh, Shibendu; Chowdhury, Subhankar; Pradhan, Manik
2015-01-01
Carbonic anhydrase (CA), a well-characterized metalloenzyme, is associated with oxygen-18 ( 18O)-isotopic fractionations of CO2. To investigate how CA activity links the 18O of breath CO2 to pre-diabetes (PD) and type 2 diabetes (T2D) during metabolism, we studied pre- and post-dose CA activities in erythrocytes with simultaneous monitoring of 18O/ 16O-isotope ratios of breath CO2 and thereafter elucidated potential metabolic pathways underlying CA alteration in the pathogenesis of T2D. Here we show that the post-dose CA activity in both T2D and PD was markedly enhanced, whereas the non-diabetic controls (NDC) exhibited a considerable reduction in post-dose CA activity when compared with their basal CA activities. However, T2D and PD exhibited isotopic enrichments of 18O in breath CO2, while a marked depletion of 18O in CO2 was manifested in NDC. Thus, the isotopic enrichments and depletions of 18O in breath CO2 were well correlated with the changes in CA activities for controls, PD and T2D. Our findings suggest the changes in CA activities in erythrocytes may contribute to the pathogenesis of T2D and the breath C 18O 16O regulated by the CA activity as a potential biomarker for non-invasive assessment of T2D, and thus may open a new method for treating T2D. PMID:25633556
NASA Astrophysics Data System (ADS)
Ahmad, Bhat Zahoor; Want, Basharat
2016-04-01
We investigate the structure and ferroelectric behavior of a lanthanide based metal-organic framework (MOF), [Nd(C4H5O6)(C4H4O6)][3H2O]. X-ray crystal structure analyses reveal that it crystallizes in the P41212 space group with Nd centres, coordinated by nine oxygen atoms, forming a distorted capped square antiprismatic geometry. The molecules, bridged by tartrate ligands, form a 2D chiral structure. The 2D sheets are further linked into a 3D porous framework via strong hydrogen-bonding scheme (O-H…O ≈ 2.113 Å). Dielectric studies reveal two anomalies at 295 K and 185 K. The former is a paraelectric-ferroelectric transition, and the later is attributed to the freezing down of the motion of the hydroxyl groups. The phase transition is of second order, and the spontaneous polarization in low temperature phase is attributed to the ordering of protons of hydroxyl groups. The dielectric nonlinearity parameters have been calculated using Landau- Devonshire phenomenological theory. In addition, the most recent semiempirical models, Sparkle/PM7, Sparkle/RM1, and Sparkle/AM1, are tested on the present system to assay the accuracy of semiempirical quantum approaches to predict the geometries of solid MOFs. Our results show that Sparkle/PM7 model is the most accurate to predict the unit cell structure and coordination polyhedron geometry. The semiempirical methods are also used to calculate different ground state molecular properties.
Neurochemical profile of dementia pugilistica.
Kokjohn, Tyler A; Maarouf, Chera L; Daugs, Ian D; Hunter, Jesse M; Whiteside, Charisse M; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A; Sabbagh, Marwan N; Beach, Thomas G; Roher, Alex E
2013-06-01
Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ-degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital.
Neurochemical Profile of Dementia Pugilistica
Kokjohn, Tyler A.; Maarouf, Chera L.; Daugs, Ian D.; Hunter, Jesse M.; Whiteside, Charisse M.; Malek-Ahmadi, Michael; Rodriguez, Emma; Kalback, Walter; Jacobson, Sandra A.; Sabbagh, Marwan N.; Beach, Thomas G.
2013-01-01
Abstract Dementia pugilistica (DP), a suite of neuropathological and cognitive function declines after chronic traumatic brain injury (TBI), is present in approximately 20% of retired boxers. Epidemiological studies indicate TBI is a risk factor for neurodegenerative disorders including Alzheimer disease (AD) and Parkinson disease (PD). Some biochemical alterations observed in AD and PD may be recapitulated in DP and other TBI persons. In this report, we investigate long-term biochemical changes in the brains of former boxers with neuropathologically confirmed DP. Our experiments revealed biochemical and cellular alterations in DP that are complementary to and extend information already provided by histological methods. ELISA and one-dimensional and two dimensional Western blot techniques revealed differential expression of select molecules between three patients with DP and three age-matched non-demented control (NDC) persons without a history of TBI. Structural changes such as disturbances in the expression and processing of glial fibrillary acidic protein, tau, and α-synuclein were evident. The levels of the Aβ–degrading enzyme neprilysin were reduced in the patients with DP. Amyloid-β levels were elevated in the DP participant with the concomitant diagnosis of AD. In addition, the levels of brain-derived neurotrophic factor and the axonal transport proteins kinesin and dynein were substantially decreased in DP relative to NDC participants. Traumatic brain injury is a risk factor for dementia development, and our findings are consistent with permanent structural and functional damage in the cerebral cortex and white matter of boxers. Understanding the precise threshold of damage needed for the induction of pathology in DP and TBI is vital. PMID:23268705
Zheng, Hongyan; Wu, Huamao; Pan, Xiaoying; Jin, Weiwei; Li, Xuexian
2017-02-01
Pollen germination is an essential step towards successful pollination during maize reproduction. How low niutrogen (N) affects pollen germination remains an interesting biological question to be addressed. We found that only low N resulted in a significantly lower germination rate of pollen grains after 4 weeks of low N, phosphorus or potassium treatment in maize production. Importantly, cytological analysis showed 7-fold more micronuclei in male meiocytes under the low N treatment than in the control, indicating that the lower germination rate of pollen grains was partially due to numerous chromosome loss events resulting from preceding meiosis. The appearance of 10 bivalents in the control and low N cells at diakinesis suggested that chromosome pairing and recombination in meiosis I was not affected by low N. Further gene expression analysis revealed dramatic down-regulation of Nuclear Division Cycle 80 (Ndc80) and Regulator of Chromosome Condensation 1 (Rcc1-1) expression and up-regulation of Cell Division Cycle 20 (Cdc20-1) expression, although no significant difference in the expression level of kinetochore foundation proteins Centromeric Histone H3 (Cenh3) and Centromere Protein C (Cenpc) and cohesion regulators Recombination 8 (Rec8) and Shugoshin (Sgo1) was observed. Aberrant modulation of three key meiotic regulators presumably resulted in a high likelihood of erroneous chromosome segregation, as testified by pronounced lagging chromosomes at anaphase I or cell cycle disruption at meiosis II. Thus, we proposed a cytogenetic mechanism whereby low N affects male meiosis and causes a higher chromosome loss frequency and eventually a lower germination rate of pollen grains in a staple crop plant. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Cryo-EM structure of Hepatitis C virus IRES bound to the human ribosome at 3.9-Å resolution
NASA Astrophysics Data System (ADS)
Quade, Nick; Boehringer, Daniel; Leibundgut, Marc; van den Heuvel, Joop; Ban, Nenad
2015-07-01
Hepatitis C virus (HCV), a widespread human pathogen, is dependent on a highly structured 5'-untranslated region of its mRNA, referred to as internal ribosome entry site (IRES), for the translation of all of its proteins. The HCV IRES initiates translation by directly binding to the small ribosomal subunit (40S), circumventing the need for many eukaryotic translation initiation factors required for mRNA scanning. Here we present the cryo-EM structure of the human 40S ribosomal subunit in complex with the HCV IRES at 3.9 Å resolution, determined by focused refinement of an 80S ribosome-HCV IRES complex. The structure reveals the molecular details of the interactions between the IRES and the 40S, showing that expansion segment 7 (ES7) of the 18S rRNA acts as a central anchor point for the HCV IRES. The structural data rationalizes previous biochemical and genetic evidence regarding the initiation mechanism of the HCV and other related IRESs.
Human Reliability and the Cost of Doing Business
NASA Technical Reports Server (NTRS)
DeMott, D. L.
2014-01-01
Human error cannot be defined unambiguously in advance of it happening, it often becomes an error after the fact. The same action can result in a tragic accident for one situation or a heroic action given a more favorable outcome. People often forget that we employ humans in business and industry for the flexibility and capability to change when needed. In complex systems, operations are driven by their specifications of the system and the system structure. People provide the flexibility to make it work. Human error has been reported as being responsible for 60%-80% of failures, accidents and incidents in high-risk industries. We don't have to accept that all human errors are inevitable. Through the use of some basic techniques, many potential human error events can be addressed. There are actions that can be taken to reduce the risk of human error.
Zhu, Yuan O.; Sherlock, Gavin; Petrov, Dmitri A.
2016-01-01
Budding yeast has undergone several independent transitions from commercial to clinical lifestyles. The frequency of such transitions suggests that clinical yeast strains are derived from environmentally available yeast populations, including commercial sources. However, despite their important role in adaptive evolution, the prevalence of polyploidy and aneuploidy has not been extensively analyzed in clinical strains. In this study, we have looked for patterns governing the transition to clinical invasion in the largest screen of clinical yeast isolates to date. In particular, we have focused on the hypothesis that ploidy changes have influenced adaptive processes. We sequenced 144 yeast strains, 132 of which are clinical isolates. We found pervasive large-scale genomic variation in both overall ploidy (34% of strains identified as 3n/4n) and individual chromosomal copy numbers (36% of strains identified as aneuploid). We also found evidence for the highly dynamic nature of yeast genomes, with 35 strains showing partial chromosomal copy number changes and eight strains showing multiple independent chromosomal events. Intriguingly, a lineage identified to be baker’s/commercial derived with a unique damaging mutation in NDC80 was particularly prone to polyploidy, with 83% of its members being triploid or tetraploid. Polyploidy was in turn associated with a >2× increase in aneuploidy rates as compared to other lineages. This dataset provides a rich source of information on the genomics of clinical yeast strains and highlights the potential importance of large-scale genomic copy variation in yeast adaptation. PMID:27317778
NASA Astrophysics Data System (ADS)
Azidin, A.; Taib, Z. A. M.; Harun, W. S. W.; Che Ghani, S. A.; Faisae, M. F.; Omar, M. A.; Ramli, H.
2015-12-01
Orthodontic implants have been a major focus through mechanical and biological performance in advance to fabricate shape of complex anatomical. Designing the part with a complex mechanism is one of the challenging process and addition to achieve the balance and desired mechanical performance brought to the right manufacture technique to fabricate. Metal additive manufacturing (MAM) is brought forward to the newest fabrication technology in this field. In this study, selective laser melting (SLM) process was utilized on a medical grade cobalt-chrome molybdenum (CoCrMo) alloy. The work has focused on mechanical properties of the CoCrMo open cellular structures samples with 60%, 70%, and 80% designed volume porosity that could potentially emulate the properties of human bone. It was observed that hardness values decreased as the soaking time increases except for bottom face. For compression test, 60% designed volume porosity demonstrated highest ultimate compressive strength compared to 70% and 80%.
Lu, Xing; Wu, Yi-Ming; Yang, Jing-Mei; Ma, Feng-E; Li, Liang-Ping; Chen, Sheng; Zhang, Ye; Ni, Qing-Ling; Pan, Ying-Ming; Hong, Xue; Peng, Yan
2018-05-10
A series of 2(1H)-quinolinone derivatives and their rhodium (III) complexes were designed and synthesized. All the rhodium (III) complexes exhibited higher in vitro cytotoxicity for Hep G2, HeLa 229, MGC80-3, and NCI-H460 human tumor cell lines than their ligands and cisplatin, and among them complex 9 was found to be selectively cytotoxic to tumor cells. Further investigation revealed that complex 9 caused cell cycle arrest at the G2/M phase and induced apoptosis, and inhibited the proliferation of Hep G2 cells by impeding the phosphorylation of epidermal growth factor receptor (EGFR) and its downstream enzymes. Complex 9 also up-regulated the proapoptotic proteins Bak, Bax, and Bim, which altogether activated caspase-3/9 to initiate cell apoptosis. Notably, complex 9 effectively inhibited tumor growth in the NCI-H460 xenograft mouse model with less adverse effect than cisplatin. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
Zhong, X; Cao, J C
2009-07-22
We study the combined effects of quantum electronic interference and Coulomb interaction on electron transport through near-degenerate molecular states with strong electron-vibration interaction. It is found that quantum electronic interference strongly affects the current and its noise properties. In particular, destructive interference induces pronounced negative differential conductances (NDCs) accompanying the vibrational excited states, and such NDC characters are not related to asymmetric tunnel coupling and are robust to the damping of a thermal bath. In a certain transport regime, the non-equilibrium vibration distribution even shows a peculiar sub-Poissonian behavior, which is enhanced by quantum electronic interference.
Yuan, Bo; Liu, Pengfei; Gupta, Aditya; Beck, Christine R.; Tejomurtula, Anusha; Campbell, Ian M.; Gambin, Tomasz; Simmons, Alexandra D.; Withers, Marjorie A.; Harris, R. Alan; Rogers, Jeffrey; Schwartz, David C.; Lupski, James R.
2015-01-01
Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100) is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs) are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases—about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR) between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV) haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual’s susceptibility to acquiring disease-associated alleles. PMID:26641089
NPE 2010 results - Independent performance assessment by simulated CTBT violation scenarios
NASA Astrophysics Data System (ADS)
Ross, O.; Bönnemann, C.; Ceranna, L.; Gestermann, N.; Hartmann, G.; Plenefisch, T.
2012-04-01
For verification of compliance to the Comprehensive Nuclear-Test-Ban Treaty (CTBT) the global International Monitoring System (IMS) is currently being built up. The IMS is designed to detect nuclear explosions through their seismic, hydroacoustic, infrasound, and radionuclide signature. The IMS data are collected, processed to analysis products, and distributed to the state signatories by the International Data Centre (IDC) in Vienna. The state signatories themselves may operate National Data Centers (NDC) giving technical advice concerning CTBT verification to the government. NDC Preparedness Exercises (NPE) are regularly performed to practice the verification procedures for the detection of nuclear explosions in the framework of CTBT monitoring. The initial focus of the NPE 2010 was on the component of radionuclide detections and the application of Atmospheric Transport Modeling (ATM) for defining the source region of a radionuclide event. The exercise was triggered by fictitious radioactive noble gas detections which were calculated beforehand secretly by forward ATM for a hypothetical xenon release scenario starting at location and time of a real seismic event. The task for the exercise participants was to find potential source events by atmospheric backtracking and to analyze in the following promising candidate events concerning their waveform signals. The study shows one possible way of solution for NPE 2010 as it was performed at German NDC by a team without precedent knowledge of the selected event and release scenario. The ATM Source Receptor Sensitivity (SRS) fields as provided by the IDC were evaluated in a logical approach in order to define probable source regions for several days before the first reported fictitious radioactive xenon finding. Additional information on likely event times was derived from xenon isotopic ratios where applicable. Of the considered seismic events in the potential source region all except one could be identified as earthquakes by seismological analysis. The remaining event at Black Thunder Mine, Wyoming, on 23 Oct at 21:15 UTC showed clear explosion characteristics. It caused also Infrasound detections at one station in Canada. An infrasonic one station localization algorithm led to event localization results comparable in precision to the teleseismic localization. However, the analysis of regional seismological stations gave the most accurate result giving an error ellipse of about 60 square kilometer. Finally a forward ATM simulation was performed with the candidate event as source in order to reproduce the original detection scenario. The ATM results showed a simulated station fingerprint in the IMS very similar to the fictitious detections given in the NPE 2010 scenario which is an additional confirmation that the event was correctly identified. The shown event analysis of the NPE 2010 serves as successful example for Data Fusion between the technology of radionuclide detection supported by ATM and seismological methodology as well as infrasound signal processing.
Interactions of the SAP Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study
NASA Technical Reports Server (NTRS)
Hu, Shaowen; Carra, Claudio; Huff, Janice; Pluth, Janice M.; Cucinotta, Francis A.
2007-01-01
NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku70/80 complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The SAP domain of Ku70 (residues 556-609), contains an a helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the SAP/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the SAP domain of Ku70 and a 10 base pairs DNA duplex. Large-scale conformational changes were observed and some putative binding modes were suggested based on energetic analysis. These modes are consistent with previous experimental investigations. In addition, the results indicate that cooperation of SAP with other domains of Ku70/80 is necessary to explain the high affinity of binding as observed in experiments.
Li, Yuqin; Wang, Hao; Jia, Baoxiu; Liu, Caihong; Liu, Ke; Qi, Yongxiu; Hu, Zhide
2013-01-01
The mechanism of interaction between deoxynivalenol (DON) and human serum albumin (HSA) was studied using spectroscopic methods including fluorescence spectra, UV-VIS, Fourier transform infrared (FT-IR) and circular dichroism (CD). The quenching mechanism was investigated in terms of the association constants, number of binding sites and basic thermodynamic parameters. The distance between the HSA donor and the acceptor DON was 2.80 nm as derived from fluorescence resonance energy transfer. The secondary structure compositions of free HSA and its DON complexes were estimated by the FT-IR spectra. Alteration of the secondary protein structure in the presence of DON was confirmed by UV-VIS and CD spectroscopy. Molecular modelling revealed that a DON-protein complex was stabilised by hydrophobic forces and hydrogen bonding. It was potentially useful for elucidating the toxigenicity of DON when combined with biomolecular function effect, transmembrane transport, toxicological testing and the other experiments.
Use of limited data to construct Bayesian networks for probabilistic risk assessment.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Groth, Katrina M.; Swiler, Laura Painton
2013-03-01
Probabilistic Risk Assessment (PRA) is a fundamental part of safety/quality assurance for nuclear power and nuclear weapons. Traditional PRA very effectively models complex hardware system risks using binary probabilistic models. However, traditional PRA models are not flexible enough to accommodate non-binary soft-causal factors, such as digital instrumentation&control, passive components, aging, common cause failure, and human errors. Bayesian Networks offer the opportunity to incorporate these risks into the PRA framework. This report describes the results of an early career LDRD project titled %E2%80%9CUse of Limited Data to Construct Bayesian Networks for Probabilistic Risk Assessment%E2%80%9D. The goal of the work was tomore » establish the capability to develop Bayesian Networks from sparse data, and to demonstrate this capability by producing a data-informed Bayesian Network for use in Human Reliability Analysis (HRA) as part of nuclear power plant Probabilistic Risk Assessment (PRA). This report summarizes the research goal and major products of the research.« less
Interactions of the C-terminal Domain of Human Ku70 with DNA Substrate: A Molecular Dynamics Study
NASA Technical Reports Server (NTRS)
Hu, Shaowen; Huff, Janice; Pluth, Janice M.; Cucinotta, Francis A.
2007-01-01
NASA is developing a systems biology approach to improve the assessment of health risks associated with space radiation. The primary toxic and mutagenic lesion following radiation exposure is the DNA double strand break (DSB), thus a model incorporating proteins and pathways important in response and repair of this lesion is critical. One key protein heterodimer for systems models of radiation effects is the Ku(sub 70/80) complex. The Ku70/80 complex is important in the initial binding of DSB ends following DNA damage, and is a component of nonhomologous end joining repair, the primary pathway for DSB repair in mammalian cells. The C-terminal domain of Ku70 (Ku70c, residues 559-609), contains an helix-extended strand-helix motif and similar motifs have been found in other nucleic acid-binding proteins critical for DNA repair. However, the exact mechanism of damage recognition and substrate specificity for the Ku heterodimer remains unclear in part due to the absence of a high-resolution structure of the Ku70c/DNA complex. We performed a series of molecular dynamics (MD) simulations on a system with the subunit Ku70c and a 14 base pairs DNA duplex, whose starting structures are designed to be variable so as to mimic their different binding modes. By analyzing conformational changes and energetic properties of the complex during MD simulations, we found that interactions are preferred at DNA ends, and within the major groove, which is consistent with previous experimental investigations. In addition, the results indicate that cooperation of Ku70c with other subunits of Ku(sub 70/80) is necessary to explain the high affinity of binding as observed in experiments.
Pitch discrimination by ferrets for simple and complex sounds.
Walker, Kerry M M; Schnupp, Jan W H; Hart-Schnupp, Sheelah M B; King, Andrew J; Bizley, Jennifer K
2009-09-01
Although many studies have examined the performance of animals in detecting a frequency change in a sequence of tones, few have measured animals' discrimination of the fundamental frequency (F0) of complex, naturalistic stimuli. Additionally, it is not yet clear if animals perceive the pitch of complex sounds along a continuous, low-to-high scale. Here, four ferrets (Mustela putorius) were trained on a two-alternative forced choice task to discriminate sounds that were higher or lower in F0 than a reference sound using pure tones and artificial vowels as stimuli. Average Weber fractions for ferrets on this task varied from approximately 20% to 80% across references (200-1200 Hz), and these fractions were similar for pure tones and vowels. These thresholds are approximately ten times higher than those typically reported for other mammals on frequency change detection tasks that use go/no-go designs. Naive human listeners outperformed ferrets on the present task, but they showed similar effects of stimulus type and reference F0. These results suggest that while non-human animals can be trained to label complex sounds as high or low in pitch, this task may be much more difficult for animals than simply detecting a frequency change.
Freij, Joudeh B.; Hann-Soden, Christopher; Taylor, John
2017-01-01
ABSTRACT Genomic analysis has placed the origins of two human-pathogenic fungi, the Cryptococcus gattii species complex and the Cryptococcus neoformans species complex, in South America and Africa, respectively. Molecular clock calculations suggest that the two species separated ~80 to 100 million years ago. This time closely approximates the breakup of the supercontinent Pangea, which gave rise to South America and Africa. On the basis of the geographic distribution of these two species complexes and the coincidence of the evolutionary divergence and Pangea breakup times, we propose that a spatial separation caused by continental drift resulted in the emergence of the C. gattii and C. neoformans species complexes from a Pangean ancestor. We note that, despite the spatial and temporal separation that occurred approximately 100 million years ago, these two species complexes are morphologically similar, share virulence factors, and cause very similar diseases. Continuation of these phenotypic characteristics despite ancient separation suggests the maintenance of similar selection pressures throughout geologic ages. PMID:28435888
Casadevall, Arturo; Freij, Joudeh B; Hann-Soden, Christopher; Taylor, John
2017-01-01
Genomic analysis has placed the origins of two human-pathogenic fungi, the Cryptococcus gattii species complex and the Cryptococcus neoformans species complex, in South America and Africa, respectively. Molecular clock calculations suggest that the two species separated ~80 to 100 million years ago. This time closely approximates the breakup of the supercontinent Pangea, which gave rise to South America and Africa. On the basis of the geographic distribution of these two species complexes and the coincidence of the evolutionary divergence and Pangea breakup times, we propose that a spatial separation caused by continental drift resulted in the emergence of the C. gattii and C. neoformans species complexes from a Pangean ancestor. We note that, despite the spatial and temporal separation that occurred approximately 100 million years ago, these two species complexes are morphologically similar, share virulence factors, and cause very similar diseases. Continuation of these phenotypic characteristics despite ancient separation suggests the maintenance of similar selection pressures throughout geologic ages.
Landucci, E C; Antunes, E; Donato, J L; Faro, R; Hyslop, S; Marangoni, S; Oliveira, B; Cirino, G; de Nucci, G
1995-01-01
1. The effect of purified crotapotin, a non-toxic non-enzymatic chaperon protein normally complexed to a phospholipase A2 (PLA2) in South America rattlesnake venom, was studied in the acute inflammatory response induced by carrageenin (1 mg/paw), compound 48/80 (3 micrograms/paw) and 5-hydroxytryptamine (5-HT) (3 micrograms/paw) in the rat hind-paw. The effects of crotapotin on platelet aggregation, mast cell degranulation and eicosanoid release from guinea-pig isolated lung were also investigated. 2. Subplantar co-injection of crotapotin (1 and 10 micrograms/paw) with carrageenin or injection of crotapotin (10 micrograms/paw) into the contralateral paw significantly inhibited the carrageenin-induced oedema. This inhibition was also observed when crotapotin (10-30 micrograms/paw) was administered either intraperitoneally or orally. Subplantar injection of heated crotapotin (15 min at 60 degrees C) failed to inhibit carrageenin-induced oedema. Subplantar injection of crotapotin (10 micrograms/paw) also significantly inhibited the rat paw oedema induced by compound 48/80, but it did not affect 5-HT-induced oedema. 3. In adrenalectomized animals, subplantar injection of crotapotin markedly inhibited the oedema induced by carrageenin. The inhibitory effect of crotapotin was also observed in rats depleted of histamine and 5-HT stores. 4. Crotapotin (30 micrograms/paw) had no effect on either the histamine release induced by compound 48/80 in vitro or on the platelet aggregation induced by both arachidonic acid (1 nM) and platelet activating factor (1 microM) in human platelet-rich plasma. The platelet aggregation and thromboxane B2 (TXB2) release induced by thrombin (100 mu ml-1) in washed human platelets were also not affected by crotapotin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7537590
Atmospheric Transport Modelling and Radionuclide Analysis for the NPE 2015 scenario
NASA Astrophysics Data System (ADS)
Ross, J. Ole; Bollhöfer, Andreas; Heidmann, Verena; Krais, Roman; Schlosser, Clemens; Gestermann, Nicolai; Ceranna, Lars
2017-04-01
The Comprehensive Nuclear-Test-Ban Treaty (CTBT) prohibits all kinds of nuclear explosions. The International Monitoring System (IMS) is in place and at about 90% complete to verify compliance with the CTBT. The stations of the waveform technologies are capable to detect seismic, hydro-acoustic and infrasonic signals for detection, localization, and characterization of explosions. For practicing Comprehensive Nuclear-Test-Ban Treaty (CTBT) verification procedures and interplay between the International Data Centre (IDC) and National Data Centres (NDC), prepardness exercises (NPE) are regularly performed with selected events of fictitious CTBT-violation. The German NDC's expertise for radionuclide analyses and operation of station RN33 is provided by the Federal Office for Radiation Protection (BfS) while Atmospheric Transport Modelling (ATM) for CTBT purposes is performed at the Federal Institute for Geosciences and Natural Resources (BGR) for the combination of the radionuclide findings with waveform evidence. The radionuclide part of the NPE 2015 scenario is tackled in a joint effort by BfS and BGR. First, the NPE 2015 spectra are analysed, fission products are identified, and respective activity concentrations are derived. Special focus is on isotopic ratios which allow for source characterization and event timing. For atmospheric backtracking the binary coincidence method is applied for both, SRS fields from IDC and WMO-RSMC, and for in-house backward simulations in higher resolution for the first affected samples. Results are compared with the WebGrape PSR and the spatio-temporal domain with high atmospheric release probability is determined. The ATM results together with the radionuclide fingerprint are used for identification of waveform candidate events. Comparative forward simulations of atmospheric dispersion for candidate events are performed. Finally the overall consistency of various source scenarios is assessed and a fictitious government briefing on the findings is given.
Monk, Jennifer M; Lepp, Dion; Zhang, Claire P; Wu, Wenqing; Zarepoor, Leila; Lu, Jenifer T; Pauls, K Peter; Tsao, Rong; Wood, Geoffrey A; Robinson, Lindsay E; Power, Krista A
2016-02-01
Common beans are rich in phenolic compounds and nondigestible fermentable components, which may help alleviate intestinal diseases. We assessed the gut health priming effect of a 20% cranberry bean flour diet from two bean varieties with differing profiles of phenolic compounds [darkening (DC) and nondarkening (NDC) cranberry beans vs. basal diet control (BD)] on critical aspects of gut health in unchallenged mice, and during dextran sodium sulfate (DSS)-induced colitis (2% DSS wt/vol, 7 days). In unchallenged mice, NDC and DC increased (i) cecal short-chain fatty acids, (ii) colon crypt height, (iii) crypt goblet cell number and mucus content and (iv) Muc1, Klf4, Relmβ and Reg3γ gene expression vs. BD, indicative of enhanced microbial activity and gut barrier function. Fecal 16S rRNA sequencing determined that beans reduced abundance of the Lactobacillaceae (Ruminococcus gnavus), Clostridiaceae (Clostridium perfringens), Peptococcaceae, Peptostreptococcaceae, Rikenellaceae and Pophyromonadaceae families, and increased abundance of S24-7 and Prevotellaceae. During colitis, beans reduced (i) disease severity and colonic histological damage, (ii) increased gene expression of barrier function promoting genes (Muc1-3, Relmβ, and Reg3γ) and (iii) reduced colonic and circulating inflammatory cytokines (IL-1β, IL-6, IFNγ and TNFα). Therefore, prior to disease induction, bean supplementation enhanced multiple concurrent gut health promoting parameters that translated into reduced colitis severity. Moreover, both bean diets exerted similar effects, indicating that differing phenolic content did not influence the endpoints assessed. These data demonstrate a proof-of-concept regarding the gut-priming potential of beans in colitis, which could be extended to mitigate the severity of other gut barrier-associated pathologies. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
The National Data Center Preparedness Exercise 2009 - First Results
NASA Astrophysics Data System (ADS)
Gestermann, Nicolai; Bönnemann, Christian; Ceranna, Lars; Wotawa, Gerhard
2010-05-01
The NDC preparedness initiative was initiated by 8 signature states. It has now a history of more than 2 years with two successful exercises and subsequent fruitful discussions during the NDC Evaluation Workshops of the CTBTO. The first exercise was carried out in 2007 (NPE07). The objectives of and the idea behind this exercise have been described in the working paper CTBT/WGB-28/DE-IT/1 of the CTBTO. The exercise simulates a fictitious violation of the CTBT and all NDCs are invited to clarify the nature of the selected event. This exercise should help to evaluate the effectiveness of analysis procedures applied at NDCs, as well as the quality, completeness, and usefulness of IDC products. Moreover, the NPE is a measure for the readiness of the NDCs to fulfil their duties in regard of the CTBT verification: the treaty compliance based judgments about the nature of events as natural or artificial and chemical or nuclear, respectively. The NPE09 has started on 1 October 2009, 00:00 UTC. In addition to the previous exercises, three technologies (seismology, infrasound, and radionuclide) have been taken into account leading to tentative mock events generated by strong explosions in open pit mines. Consequently, the first event, which fulfils all previously defined criteria, was close to the Kara-Zhyra mine in Eastern Kazakhstan and occurred on 28 November 2009 at 07:20:31 UTC. It generated seismic signals as well as infrasound signals at the closest IMS stations. The forward atmospheric transport modelling indicated that a sufficient number of radionuclide stations were also affected to enable the application of a negative testing scenario. First results of the seismo-acoustic analysis of the NPE09 event were presented along with details on the event selection process.
Translating concepts of complexity to the field of ergonomics.
Walker, Guy H; Stanton, Neville A; Salmon, Paul M; Jenkins, Daniel P; Rafferty, Laura
2010-10-01
Since 1958 more than 80 journal papers from the mainstream ergonomics literature have used either the words 'complex' or 'complexity' in their titles. Of those, more than 90% have been published in only the past 20 years. This observation communicates something interesting about the way in which contemporary ergonomics problems are being understood. The study of complexity itself derives from non-linear mathematics but many of its core concepts have found analogies in numerous non-mathematical domains. Set against this cross-disciplinary background, the current paper aims to provide a similar initial mapping to the field of ergonomics. In it, the ergonomics problem space, complexity metrics and powerful concepts such as emergence raise complexity to the status of an important contingency factor in achieving a match between ergonomics problems and ergonomics methods. The concept of relative predictive efficiency is used to illustrate how this match could be achieved in practice. What is clear overall is that a major source of, and solution to, complexity are the humans in systems. Understanding complexity on its own terms offers the potential to leverage disproportionate effects from ergonomics interventions and to tighten up the often loose usage of the term in the titles of ergonomics papers. STATEMENT OF RELEVANCE: This paper reviews and discusses concepts from the study of complexity and maps them to ergonomics problems and methods. It concludes that humans are a major source of and solution to complexity in systems and that complexity is a powerful contingency factor, which should be considered to ensure that ergonomics approaches match the true nature of ergonomics problems.
Mase, Yuri; Ishibashi, Osamu; Ishikawa, Tomoko; Takizawa, Takami; Kiguchi, Kazushige; Ohba, Takashi; Katabuchi, Hidetaka; Takeshita, Toshiyuki; Takizawa, Toshihiro
2012-10-01
MicroRNAs (miRNAs) are noncoding small RNAs that play important roles in a variety of physiological and pathological events. In this study, we performed large-scale profiling of EIF2C2-bound miRNAs in 3 human granulosa-derived cell lines (ie, KGN, HSOGT, and GC1a) by high-throughput sequencing and found that miR-21 accounted for more than 80% of EIF2C2-bound miRNAs, suggesting that it was enriched in the RNA-induced silencing complex (RISC) and played a functional role in human granulosa cell (GC) lines. We also found high expression levels of miR-21 in primary human GCs. Assuming that miR-21 target mRNAs are enriched in RISC, we performed cDNA cloning of EIF2C2-bound mRNAs in KGN cells. We identified COL4A1 mRNA as a miR-21 target in the GC lines. These data suggest that miR-21 is involved in the regulation of the synthesis of COL4A1, a component of the basement membrane surrounding the GC layer and granulosa-embedded extracellular structure.
The radioisotope complex project “RIC-80” at the Petersburg Nuclear Physics Institute
DOE Office of Scientific and Technical Information (OSTI.GOV)
Panteleev, V. N., E-mail: vnp@pnpi.spb.ru; Barzakh, A. E.; Batist, L. Kh.
2015-12-15
The high current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed at Petersburg Nuclear Physics Institute. One of the main goals of the C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. The project development of the radioisotope complex RIC-80 (radioisotopes at the cyclotron C-80) at the beam of C-80 has been completed. The RIC-80 complex is briefly discussed in this paper. The combination of the mass-separator with the target-ion source device, available at one of the new target stations for on-linemore » or semi on-line production of a high purity separated radioisotopes, is explored in greater detail. The results of target and ion source tests for a mass-separator method for the production of high purity radioisotopes {sup 82}Sr and {sup 223,224}Ra are also presented.« less
The radioisotope complex project "RIC-80" at the Petersburg Nuclear Physics Institute.
Panteleev, V N; Barzakh, A E; Batist, L Kh; Fedorov, D V; Ivanov, V S; Moroz, F V; Molkanov, P L; Orlov, S Yu; Volkov, Yu M
2015-12-01
The high current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed at Petersburg Nuclear Physics Institute. One of the main goals of the C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. The project development of the radioisotope complex RIC-80 (radioisotopes at the cyclotron C-80) at the beam of C-80 has been completed. The RIC-80 complex is briefly discussed in this paper. The combination of the mass-separator with the target-ion source device, available at one of the new target stations for on-line or semi on-line production of a high purity separated radioisotopes, is explored in greater detail. The results of target and ion source tests for a mass-separator method for the production of high purity radioisotopes (82)Sr and (223,224)Ra are also presented.
Disaster complexity and the Santiago de Compostela train derailment
Shultz, James M.; Garcia-Vera, Maria Paz; Santos, Clara Gesteira; Sanz, Jesús; Bibel, George; Schulman, Carl; Bahouth, George; Dias Guichot, Yasmin; Espinel, Zelde; Rechkemmer, Andreas
2016-01-01
ABSTRACT This disaster complexity case study examines Spain's deadliest train derailment that occurred on July 24, 2013 on the outskirts of Santiago de Compostela, Galicia, Spain. Train derailments are typically survivable. However, in this case, human error was a primary factor as the train driver powered the Alvia train into a left curve at more than twice the posted speed. All 13 cars came off the rails with many of the carriages careening into a concrete barrier lining the curve, leading to exceptional mortality and injury. Among the 224 train occupants, 80 (36%) were killed and all of the remaining 144 (4%) were injured. The official investigative report determined that this crash was completely preventable. PMID:28265487
A Methodological Review of the Assessment of Humanism in Medical Students.
Buck, Era; Holden, Mark; Szauter, Karen
2015-11-01
Humanism is a complex construct that defies simplistic measurement. How educators measure humanism shapes understanding and implications for learners. This systematic review sought to address the following questions: How do medical educators assess humanism in medical students, and how does the measurement impact the understanding of humanism in undergraduate medical education (UME)? Using the IECARES (integrity, excellence, compassion, altruism, respect, empathy, and service) Gold Foundation framework, a search of English literature databases from 2000 to 2013 on assessment of humanism in medical students revealed more than 900 articles, of which 155 met criteria for analysis. Using descriptive statistics, articles and assessments were analyzed for construct measured, study design, assessment method, instrument type, perspective/source of assessment, student level, validity evidence, and national context. Of 202 assessments reported in 155 articles, 162 (80%) used surveys; 164 (81%) used student self-reports. One hundred nine articles (70%) included only one humanism construct. Empathy was the most prevalent construct present in 96 (62%); 49 (51%) of those used a single instrument. One hundred fifteen (74%) used exclusively quantitative data; only 48 (31%) used a longitudinal design. Construct underrepresentation was identified as a threat to validity in half of the assessments. Articles included 34 countries; 87 (56%) were from North America. Assessment of humanism in UME incorporates a limited scope of a complex construct, often relying on single quantitative measures from self-reported survey instruments. This highlights the need for multiple methods, perspectives, and longitudinal designs to strengthen the validity of humanism assessments.
Tris[dimethyl (benzoylamido)phosphato-κ2 O,O′](1,10-phenanthroline-κ2 N,N′)neodymium(III)
Kariaka, Nataliia S.; Trush, Victor A.; Medviediev, Volodymyr V.; Sliva, Tetyana Yu.; Amirkhanov, Vladimir M.
2013-01-01
In both independent molecules of the title compound, [Nd(C9H11NO4P)3(C12H8N2)], the NdIII atom is coordinated by six O atoms belonging to three phosphoryl ligands and two N atoms of 1,10-phenanthroline in a dodecahedral geometry. In the phosphoryl ligands, the benzene rings are twisted with respect to the planes of the sp 2-hybridized C atoms of the chelate rings by 12.1 (1)–24.7 (1)°. PMID:23476491
Study of the performance of the infrasound Station IS48TN during the period 2011 -2017
NASA Astrophysics Data System (ADS)
Mejri, Chourouk
2017-04-01
The Infrasound Station IS48, in Kesra, Tunisia is part of the verification regime for the Comprehensive Nuclear-Test-Ban Treaty. IS48 is managed and maintained by the Tunisian NDC. Its good location in the middle of the Mediterranean Sea allows to have various and interesting detections. Several events were recorded and identified. But since 2010, the performance of the station has began to be noisy , due to a leakage in the pipe array, despite efforts to solve the issue through the pressure test and maintenance . To this issues, PTS decided to upgrade the WNRS at IS48TN.
Dimensionality effects in chalcogenide-based devices
NASA Astrophysics Data System (ADS)
Kostylev, S. A.
2013-06-01
The multiplicity of fundamental bulk effects with small characteristic dimensions and short times and diversity of their combinations attracts a lot of researcher and industrialist attention in nanoelectronics and photonics to chalcogenide materials. Experimental data presented on dimensional effects of electrical chalcogenide switching (threshold voltage and threshold current dependence on device area and the film thickness), and in phase-change memory (switching, programming and read parameters), are analyzed from the point of view of choice of low dimensional materials with S-NDC and participation of electrical instabilities - high current density filaments. New ways of improving parameters of phase-change devices are proposed together with new criteria of material choice.
Manor, Brad; Costa, Madalena D; Hu, Kun; Newton, Elizabeth; Starobinets, Olga; Kang, Hyun Gu; Peng, C K; Novak, Vera; Lipsitz, Lewis A
2010-12-01
The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (<20/40 vision, n = 81, 77 ± 4 yr old), somatosensory impairment only (inability to perceive 5.07 monofilament on plantar halluxes, n = 48, 80 ± 5 yr old), and combined impairments (n = 25, 80 ± 4 yr old). Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P < 0.01). Lower complexity during quiet standing correlated with greater absolute (R = -0.34, P = 0.002) and percent (R = -0.45, P < 0.001) increases in postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors.
Costa, Madalena D.; Hu, Kun; Newton, Elizabeth; Starobinets, Olga; Kang, Hyun Gu; Peng, C. K.; Novak, Vera; Lipsitz, Lewis A.
2010-01-01
The degree of multiscale complexity in human behavioral regulation, such as that required for postural control, appears to decrease with advanced aging or disease. To help delineate causes and functional consequences of complexity loss, we examined the effects of visual and somatosensory impairment on the complexity of postural sway during quiet standing and its relationship to postural adaptation to cognitive dual tasking. Participants of the MOBILIZE Boston Study were classified into mutually exclusive groups: controls [intact vision and foot somatosensation, n = 299, 76 ± 5 (SD) yr old], visual impairment only (<20/40 vision, n = 81, 77 ± 4 yr old), somatosensory impairment only (inability to perceive 5.07 monofilament on plantar halluxes, n = 48, 80 ± 5 yr old), and combined impairments (n = 25, 80 ± 4 yr old). Postural sway (i.e., center-of-pressure) dynamics were assessed during quiet standing and cognitive dual tasking, and a complexity index was quantified using multiscale entropy analysis. Postural sway speed and area, which did not correlate with complexity, were also computed. During quiet standing, the complexity index (mean ± SD) was highest in controls (9.5 ± 1.2) and successively lower in the visual (9.1 ± 1.1), somatosensory (8.6 ± 1.6), and combined (7.8 ± 1.3) impairment groups (P = 0.001). Dual tasking resulted in increased sway speed and area but reduced complexity (P < 0.01). Lower complexity during quiet standing correlated with greater absolute (R = −0.34, P = 0.002) and percent (R = −0.45, P < 0.001) increases in postural sway speed from quiet standing to dual-tasking conditions. Sensory impairments contributed to decreased postural sway complexity, which reflected reduced adaptive capacity of the postural control system. Relatively low baseline complexity may, therefore, indicate control systems that are more vulnerable to cognitive and other stressors. PMID:20947715
Suau, Antonia; Bonnet, Régis; Sutren, Malène; Godon, Jean-Jacques; Gibson, Glenn R.; Collins, Matthew D.; Doré, Joel
1999-01-01
The human intestinal tract harbors a complex microbial ecosystem which plays a key role in nutrition and health. Although this microbiota has been studied in great detail by culture techniques, microscopic counts on human feces suggest that 60 to 80% of the observable bacteria cannot be cultivated. Using comparative analysis of cloned 16S rRNA gene (rDNA) sequences, we have investigated the bacterial diversity (both cultivated and noncultivated bacteria) within an adult-male fecal sample. The 284 clones obtained from 10-cycle PCR were classified into 82 molecular species (at least 98% similarity). Three phylogenetic groups contained 95% of the clones: the Bacteroides group, the Clostridium coccoides group, and the Clostridium leptum subgroup. The remaining clones were distributed among a variety of phylogenetic clusters. Only 24% of the molecular species recovered corresponded to described organisms (those whose sequences were available in public databases), and all of these were established members of the dominant human fecal flora (e.g., Bacteroides thetaiotaomicron, Fusobacterium prausnitzii, and Eubacterium rectale). However, the majority of generated rDNA sequences (76%) did not correspond to known organisms and clearly derived from hitherto unknown species within this human gut microflora. PMID:10543789
Functional Proteomic Analysis of Lipid Raft Kinase Complexes
2009-08-01
Ribosomal protein SA Raft 12 46/300 + 16.0 8.0 2.0 18 8 2.3 14 6 2.3 712 + + IPI00023101 RQCD1 Homo sapiens protein involved in sexual development...KnownHuman 17-ODYA IPI00065486 ABCB6 CDNA FLJ32464 fis, clone SKNMC1000251, highly similar to Homo sapiens MT-ABCtransporter (MTABC) mRNA IPI00006675...3.7 : 0 + + IPI00023101 RQCD1 Homo sapiens protein involved in sexual development, complete cds + + IPI00021766 RTN4 Isoform 1 of Reticulon-4 12
Atomistic Simulations of Complex DNA DSBs and the Interactions with Ku70/80 Heterodimer
NASA Technical Reports Server (NTRS)
Hu, Shaowen; Cucinotta, Francis A.
2011-01-01
Compared to DNA with simple DSBs, the complex lesions can enhance the hydrogen bonds opening rate at the DNA terminus, and increase the mobility of the whole duplex. Binding of Ku drastically reduces the structural disruption and flexibility caused by the complex lesions. In all complex DSBs systems, the binding of DSB terminus with Ku70 is softened while the binding of the middle duplex with Ku80 is tightened. Binding of Ku promotes the rigidity of DNA duplexes, due to the clamp structure of the inner surface of the rings of Ku70/80.
Determination of teicoplanin concentrations in serum by high-pressure liquid chromatography.
Joos, B; Lüthy, R
1987-01-01
An isocratic reversed-phase high-pressure liquid chromatographic method for the determination of six components of the teicoplanin complex in biological fluid was developed. By using fluorescence detection after precolumn derivatization with fluorescamine, the assay is specific and highly sensitive, with reproducibility studies yielding coefficients of variation ranging from 1.5 to 8.5% (at 5 to 80 micrograms/ml). Response was linear from 2.5 to 80 micrograms/ml (r = 0.999); the recovery from spiked human serum was 76%. An external quality control was performed to compare this high-pressure liquid chromatographic method (H) with a standard microbiological assay (M); no significant deviation from slope = 1 and intercept = 0 was found by regression analysis (H = 1.03M - 0.45; n = 15). PMID:2957953
Cell diversity and network dynamics in photosensitive human brain organoids
Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z.; Sherwood, John L.; Yang, Sung Min; Berger, Daniel; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin; Boyden, Edward S.; Lichtman, Jeff; Williams, Ziv M.; McCarroll, Steven A.; Arlotta, Paola
2017-01-01
In vitro models of the developing brain such as 3D brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, it remains undefined what cells are generated within organoids and to what extent they recapitulate the regional complexity, cellular diversity, and circuit functionality of the brain. Here, we analyzed gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (over 9 months) enabling unprecedented levels of maturity including the formation of dendritic spines and of spontaneously-active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photoreceptor-like cells, which may offer ways to probe the functionality of human neuronal circuits using physiological sensory stimuli. PMID:28445462
Cell diversity and network dynamics in photosensitive human brain organoids.
Quadrato, Giorgia; Nguyen, Tuan; Macosko, Evan Z; Sherwood, John L; Min Yang, Sung; Berger, Daniel R; Maria, Natalie; Scholvin, Jorg; Goldman, Melissa; Kinney, Justin P; Boyden, Edward S; Lichtman, Jeff W; Williams, Ziv M; McCarroll, Steven A; Arlotta, Paola
2017-05-04
In vitro models of the developing brain such as three-dimensional brain organoids offer an unprecedented opportunity to study aspects of human brain development and disease. However, the cells generated within organoids and the extent to which they recapitulate the regional complexity, cellular diversity and circuit functionality of the brain remain undefined. Here we analyse gene expression in over 80,000 individual cells isolated from 31 human brain organoids. We find that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina. Organoids could be developed over extended periods (more than 9 months), allowing for the establishment of relatively mature features, including the formation of dendritic spines and spontaneously active neuronal networks. Finally, neuronal activity within organoids could be controlled using light stimulation of photosensitive cells, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.
Tabrizi, Leila; Chiniforoshan, Hossein
2017-02-01
Three new platinum(II) complexes of lidocaine and phenylcyanamide derivative ligands of formula K[Pt(3,5-(NO 2 ) 2 pcyd) 2 (LC)], 1, K[Pt(3,5-(CF 3 ) 2 pcyd) 2 (LC)], 2, K[Pt(3,5-Cl 2 pcyd) 2 (LC)], 3 (LC: lidocaine, 3,5-(NO 2 ) 2 pcyd: 3,5-dinitro phenylcyanamide, 3,5-(CF 3 ) 2 pcyd: 3,5-bis(trifluoromethyl) phenylcyanamide, 3,5-Cl 2 pcyd: 3,5-dichloro phenylcyanamide) have been synthesized and fully characterized. Cellular uptake, DNA platination and cytotoxicity against a panel of human tumor cell lines were evaluated. The complexes 1-3 revealed a significant in vitro antiproliferative activity against human ovarian carcinoma (A2780), colorectal adenocarcinoma (HT29), breast (MCF-7), liver hepatocellular carcinoma (HepG-2) and lung adenocarcinoma (A549) cancer cell lines. All the complexes are more active than cisplatin and follow the trend 1 > 2 > 3. Mechanistic studies showed that the trend in cytotoxicity of the Pt(II) complexes is mainly consistent with their ability to accumulate into cancer cells and to increase intracellular basal reactive oxygen species levels, which consequently results in the loss of mitochondrial membrane potential and apoptosis induction. The complex 1 caused to approximately 80-fold higher DNA platination level with respect to cisplatin. The complexes 1-3 can considerably stimulate the production of hydrogen peroxide in a time-dependent manner. Also, the complexes 1-3 induced an increase in reactive oxygen species (ROS) production that was superior to that induced by antimycin. The complex 1 had the most effect on ROS production in comparison with other complexes.
McConnell, Michael J; Moran, John V; Abyzov, Alexej; Akbarian, Schahram; Bae, Taejeong; Cortes-Ciriano, Isidro; Erwin, Jennifer A; Fasching, Liana; Flasch, Diane A; Freed, Donald; Ganz, Javier; Jaffe, Andrew E; Kwan, Kenneth Y; Kwon, Minseok; Lodato, Michael A; Mills, Ryan E; Paquola, Apua C M; Rodin, Rachel E; Rosenbluh, Chaggai; Sestan, Nenad; Sherman, Maxwell A; Shin, Joo Heon; Song, Saera; Straub, Richard E; Thorpe, Jeremy; Weinberger, Daniel R; Urban, Alexander E; Zhou, Bo; Gage, Fred H; Lehner, Thomas; Senthil, Geetha; Walsh, Christopher A; Chess, Andrew; Courchesne, Eric; Gleeson, Joseph G; Kidd, Jeffrey M; Park, Peter J; Pevsner, Jonathan; Vaccarino, Flora M
2017-04-28
Neuropsychiatric disorders have a complex genetic architecture. Human genetic population-based studies have identified numerous heritable sequence and structural genomic variants associated with susceptibility to neuropsychiatric disease. However, these germline variants do not fully account for disease risk. During brain development, progenitor cells undergo billions of cell divisions to generate the ~80 billion neurons in the brain. The failure to accurately repair DNA damage arising during replication, transcription, and cellular metabolism amid this dramatic cellular expansion can lead to somatic mutations. Somatic mutations that alter subsets of neuronal transcriptomes and proteomes can, in turn, affect cell proliferation and survival and lead to neurodevelopmental disorders. The long life span of individual neurons and the direct relationship between neural circuits and behavior suggest that somatic mutations in small populations of neurons can significantly affect individual neurodevelopment. The Brain Somatic Mosaicism Network has been founded to study somatic mosaicism both in neurotypical human brains and in the context of complex neuropsychiatric disorders. Copyright © 2017, American Association for the Advancement of Science.
NASA Astrophysics Data System (ADS)
Jayamani, Arumugam; Sethupathi, Murugan; Ojwach, Stephen O.; Sengottuvelan, Nallathambi
2018-01-01
Reactions of monoanionic bidentate ligands 5-methylsalicylaldehyde (5-msal), 5-bromosalicylaldehyde (5-brsal), 5-nitrosalicylaldehyde (5-nsal) and 2-hydroxy-1-naphthaldehyde (2-hnap) with nickel perchlorate hexahydrate produced nickel(II) complexes 1-4, respectively. Single crystal X-ray analyses of complexes 1 and 2 confirmed bidentate mode of the ligands with O˄O coordination to give square planar geometry around nickel atoms. Complexes 1-4 showed one quasi-reversible redox peak at cathodic region (-0.67 to -0.80 V) and one redox peak at anodic region (+1.08 to +1.44 V) assignable to the Ni(II)/Ni(I) and Ni(II)/Ni(III) redox couples, respectively. The complexes exhibited good bovine serum albumin (BSA) binding abilities with a maximum binding constant of 1.96 × 105 M-1. The binding of complexes with calf thymus DNA (ctDNA) showed that the binding affinity is consistent with an increase in steric bulk of the ligands. The nuclease activity of the complexes showed efficient oxidative cleavage in the presence of hydrogen peroxide as an oxidizing agent. The complexes showed higher zone of inhibition when screened for antimicrobial activity against bacteria and human pathogenic fungi.
Ku80 Counters Oxidative Stress-Induced DNA Damage and Cataract Formation in the Human Lens.
Smith, Andrew John Oliver; Ball, Simon Sidney Robert; Manzar, Kamal; Bowater, Richard Peter; Wormstone, Ian Michael
2015-12-01
Oxidative stress in the human lens leads to a wide range of damage including DNA strand breaks, which are likely to contribute to cataract formation. The protein Ku80 is a fundamental component of the nonhomologous end-joining pathway that repairs DNA double strand breaks. This study investigates the putative impact of Ku80 in cataract prevention in the human lens. The present study used the human lens epithelial cell line FHL124 and whole human lens organ culture. Targeted siRNA was used to deplete Ku80, with Western blot and immunocytochemistry employed to assess Ku80 expression levels. Oxidative stress was induced with hydrogen peroxide and DNA strand breaks measured by alkaline comet assay and γH2AX foci counts. Visual quality of whole human lenses was measured with image analysis software. Expression of Ku80 was predominately found in the cell nucleus of both FHL124 cells and native human lens epithelium. Treatment of FHL124 cells and whole lens cultures with siRNA targeted against Ku80 resulted in a significant knockdown at the protein level. Application of oxidative stress (30 μM H2O2) created more DNA strand breaks when added to Ku80 knockdown cells than in scrambled siRNA control cells as determined by the alkaline comet assay and the number of γH2AX foci. In whole lens cultures, exposure to 1 mM H2O2 resulted in more lens opacity in Ku80 knockdown lenses than match-paired controls. Depletion of Ku80 in the lens through acute change or a consequence of aging is likely to increase levels of DNA strand breaks, which could negatively influence physiological function and promote lens opacity. It is therefore feasible that Ku80 plays a role in retarding cataract formation.
Test Area C-80 Complex Final Range Environmental Assessment, Revision 1
2009-08-14
C-80 Complex include gaseous chemical materials from current use of ordnance, smokes, and flares, as well as depleted uranium on TA C-80B from...Smoke grenades (various) 430 Flares (various) 430 OS-4 smoke pot 430 C-80B 466 Fog oil 1,000 gallons Ictus nickel foreign weapon exploitation 20...2007b DU = depleted uranium ; ERP = Environmental Restoration Program; LUC = land use control; POI = point of interest A ffected E nvironm ent C hem
NASA Astrophysics Data System (ADS)
Xu, Huidong
Negative differential conductivity (NDC) is a nonlinear property of electronic transport for high electric field strength found in materials and devices such as semiconductor superlattices, bulk GaAs and Gunn diodes. In spatially extended systems, NDC can cause rich dynamics such as static and mobile field domains and moving charge fronts. In this thesis, these phenomena are studied theoretically and numerically for semiconductor superlattices. Two classes of models are considered: a discrete model based on sequential resonant tunneling between neighboring quantum wells is used to described charge transport in weakly-coupled superlattices, and a continuum model based on the miniband transport is used to describe charge transport strongly-coupled superlattices. The superlattice is a spatially extended nonlinear system consisting a periodic arrangement of quantum wells (e.g., GaAs) and barriers (e.g., AlAs). Using a discrete model and only considering one spatial dimension, we find that the boundary condition at the injecting contact has a great influence on the dynamical behavior for both fixed voltage and transient response. Static or moving field domains are usually inevitable in this system. In order to suppress field domains, we add a side shunting layer parallel to the growth direction of the superlattice. In this case, the model includes both vertical and lateral spatial degrees of freedom. We first study a shunted weakly-coupled superlattice for a wide range of material parameters. The field domains are found to be suppressed for superlattices with small lateral size and good connection between the shunt and the quantum wells of the superlattice. As the lateral size of the superlattice increases, the uniform field configuration loses its stability to either static or dynamic field domains, regardless of shunt properties. A lower quality shunt generally leads to regular and chaotic current oscillations and complex spatio-temporal dynamics in the field profile. Bifurcations separating static and dynamic behaviors are characterized and found to be dependent on the shunt properties. Then we adopt the model to study the shunted strongly-coupled superlattice with the continuum model. Key structural parameters associated with both the shunt layer and SL are identified for which the shunt layer stabilizes a uniform electric field profile. These results support the possibility to realize a SL-based THz oscillator with a carefully designed structure. Another important behavior of the static field domains in the weakly-coupled superlattice is bistability, i.e., two possible states (i.e., electric field configurations) for a single voltage. Noise can drive the system from one of these states (the metastable state) to the other one (the globally stable state). The process of escape from the metastable state can be viewed as a stochastic first-passage process in a high-dimensional system that possesses complex stability eigenvalues and for which a global potential energy function does not exist. This process is simulated using a stochastic differential equation system which incorporates shot noise. The mean switching time tau is fitted to an exponential expression e1DVth -Va, where Vth denotes the voltage at the end of the current branch. The exponent alpha in the fitting curve deviates from 1.5 which is predicted for a generic one dimensional system. We develop an algorithm to determine an effective locally valid potential. Principal component analysis is applied to find the most probable path for switching from the metastable current state.
Anjomshoa, Marzieh; Hadadzadeh, Hassan; Torkzadeh-Mahani, Masoud; Fatemi, Seyed Jamilaldin; Adeli-Sardou, Mahboubeh; Rudbari, Hadi Amiri; Nardo, Viviana Mollica
2015-01-01
The copper(II) complex of 1,2,4-triazine derivatives, [Cu(dppt)2(H2O)](PF6)2(dppt is 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine), has been synthesized and fully characterized by spectroscopic methods and single crystal X-ray diffraction. The in vitro DNA-binding studies of the complex have been investigated by several methods. The results showed that the complex intercalates into the base pairs of DNA. The complex also indicated good binding propensity to BSA. The results of molecular docking and molecular dynamic simulation methods confirm the experimental results. Finally, the in vitro cytotoxicity indicate that the complex has excellent anticancer activity against the three human carcinoma cell lines, MCF-7, A-549, and HT-29, with IC50 values of 9.8, 7.80, and 4.50 μM, respectively. The microscopic analyses of the cancer cells demonstrate that the Cu(II) complex apparently induced apoptosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.
2016-01-01
Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753
Diez, M C; Pouleurs, D; Navia, R; Vidal, G
2005-09-01
The effect of ethylenediaminetetracetic acid (EDTA) and Fe-EDTA complex on synthetic totally chlorine-free (TCF) effluent degradability in batch and continuously operating reactors was evaluated. Under batch treatment, the addition of EDTA and Fe-EDTA complex was studied in the range of 80 to 320 mg l(-1). Under continuously operated reactors, the Fe-EDTA complex concentration varied from 20 to 80 mg l(-1), and the hydraulic retention time (HRT) varied from 48 to 24 h. Sludge oxygen uptake rate (OUR) and chemical oxygen demand (COD) removal decreased when EDTA concentration increased in the influent under batch treatment; however, this inhibitory effect was reduced by the addition of Fe-EDTA complex. Without the addition of EDTA, COD removal decreased from 71% to 8%. The most efficient EDTA removal treatment (almost 10%) was the treatment of 80 mg l(-1) Fe-EDTA. Under continuously operated reactors, COD removal was greater than 57% in the synthetic TCF effluent with a Fe-EDTA concentration that varied from 20 to 80 mg l(-1); however, EDTA removal was lower than 25% in all cases. Synthetic TCF effluent with a Fe -EDTA concentration higher than 80 mg l(-1) could not be treated by the activated sludge treatment due to EDTA's inhibitory effect on the sludge.
Gene therapy restores auditory and vestibular function in a mouse model of Usher syndrome type 1c.
Pan, Bifeng; Askew, Charles; Galvin, Alice; Heman-Ackah, Selena; Asai, Yukako; Indzhykulian, Artur A; Jodelka, Francine M; Hastings, Michelle L; Lentz, Jennifer J; Vandenberghe, Luk H; Holt, Jeffrey R; Géléoc, Gwenaëlle S
2017-03-01
Because there are currently no biological treatments for hearing loss, we sought to advance gene therapy approaches to treat genetic deafness. We focused on Usher syndrome, a devastating genetic disorder that causes blindness, balance disorders and profound deafness, and studied a knock-in mouse model, Ush1c c.216G>A, for Usher syndrome type IC (USH1C). As restoration of complex auditory and balance function is likely to require gene delivery systems that target auditory and vestibular sensory cells with high efficiency, we delivered wild-type Ush1c into the inner ear of Ush1c c.216G>A mice using a synthetic adeno-associated viral vector, Anc80L65, shown to transduce 80-90% of sensory hair cells. We demonstrate recovery of gene and protein expression, restoration of sensory cell function, rescue of complex auditory function and recovery of hearing and balance behavior to near wild-type levels. The data represent unprecedented recovery of inner ear function and suggest that biological therapies to treat deafness may be suitable for translation to humans with genetic inner ear disorders.
Hennequin, Martine; Moysan, Véronique; Jourdan, Didier; Dorin, Martine; Nicolas, Emmanuel
2008-01-01
Background Despite wide recognition that children with disability often have poor oral health, few high quality, controlled results are available. Method Twenty-four objective and subjective criteria covering feeding, autonomy, access to dental care, oral hygiene, oral disease, general health and behavior were evaluated in a observational cross-sectional study of 2,487 children with disability (DC group), 4,772 adolescents with disability (DA group) and 1,641 children without disability (NDC group). Five algorithms ranked the subjects according to clinical criteria in three original oral health indices: the Clinical Oral Health Index (COHI), indicating the level of oral health problems, the Clinical Oral Care Needs Index (COCNI) giving dental care need levels, and the Clinical Oral Prevention Index (COPI) determining possible needs in terms of dental education initiatives. Results DC-group children presented poorer oral health and had greater needs in both treatment and preventive oral health actions than NDC-group children (OR = 3.97, 95% CI = 3.25–4.86 for COHI; OR = 2.01, 95% CI = 1.77–2.28 for COCNI; OR = 5.25, 95% CI = 4.55–6.02 for COPI). These conditions were worse again in the DA group comparing to the DC group (OR = 3.52, 95% CI = 2.7–4.6 for COHI; OR = 1.52, 95% CI = 1.38–1.69 for COCNI; OR = 1.53, 95% CI = 1.39–1.69 for COPI). Conclusion Clinical indices generated by algorithmic association of various clinical indicators allow sensitive clinical measurement, and in this study demonstrated inequalities in oral health for children with disabilities schooling in institutions. Questions need now to be addressed as to the measures that could be taken to compensate for this situation. PMID:18575600
Kalifa, Lidza; Quintana, Daniel F; Schiraldi, Laura K; Phadnis, Naina; Coles, Garry L; Sia, Rey A; Sia, Elaine A
2012-03-01
Mitochondrial DNA (mtDNA) deletions are associated with sporadic and inherited diseases and age-associated neurodegenerative disorders. Approximately 85% of mtDNA deletions identified in humans are flanked by short directly repeated sequences; however, mechanisms by which these deletions arise are unknown. A limitation in deciphering these mechanisms is the essential nature of the mitochondrial genome in most living cells. One exception is budding yeast, which are facultative anaerobes and one of the few organisms for which directed mtDNA manipulation is possible. Using this model system, we have developed a system to simultaneously monitor spontaneous direct-repeat-mediated deletions (DRMDs) in the nuclear and mitochondrial genomes. In addition, the mitochondrial DRMD reporter contains a unique KpnI restriction endonuclease recognition site that is not present in otherwise wild-type (WT) mtDNA. We have expressed KpnI fused to a mitochondrial localization signal to induce a specific mitochondrial double-strand break (mtDSB). Here we report that loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs. Furthermore, our data support homologous recombination (HR) as the predominant pathway by which mtDNA deletions arise in yeast, and suggest that the MRX and Ku70/80 complexes are partially redundant in mitochondria.
Kalifa, Lidza; Quintana, Daniel F.; Schiraldi, Laura K.; Phadnis, Naina; Coles, Garry L.; Sia, Rey A.; Sia, Elaine A.
2012-01-01
Mitochondrial DNA (mtDNA) deletions are associated with sporadic and inherited diseases and age-associated neurodegenerative disorders. Approximately 85% of mtDNA deletions identified in humans are flanked by short directly repeated sequences; however, mechanisms by which these deletions arise are unknown. A limitation in deciphering these mechanisms is the essential nature of the mitochondrial genome in most living cells. One exception is budding yeast, which are facultative anaerobes and one of the few organisms for which directed mtDNA manipulation is possible. Using this model system, we have developed a system to simultaneously monitor spontaneous direct-repeat–mediated deletions (DRMDs) in the nuclear and mitochondrial genomes. In addition, the mitochondrial DRMD reporter contains a unique KpnI restriction endonuclease recognition site that is not present in otherwise wild-type (WT) mtDNA. We have expressed KpnI fused to a mitochondrial localization signal to induce a specific mitochondrial double-strand break (mtDSB). Here we report that loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) complexes significantly impacts the rate of spontaneous deletion events in mtDNA, and these proteins contribute to the repair of induced mtDSBs. Furthermore, our data support homologous recombination (HR) as the predominant pathway by which mtDNA deletions arise in yeast, and suggest that the MRX and Ku70/80 complexes are partially redundant in mitochondria. PMID:22214610
Identification of 80K-H as a protein involved in GLUT4 vesicle trafficking
2005-01-01
PKCζ (protein kinase Cζ) is a serine/threonine protein kinase controlled by insulin, various growth factors and phosphoinositide 3-kinase. It has been implicated in controlling glucose transport in response to insulin by the translocation of GLUT4-(glucose transporter 4) containing vesicles to the plasma membrane in stimulated cells. How PKCζ modulates GLUT4 vesicle trafficking remains unknown. A yeast two-hybrid screen using full-length human PKCζ identified 80K-H protein as an interactor with PKCζ. GST (glutathione S-transferase) pull-down assays with GST-tagged 80K-H constructs confirmed the interaction and showed that the N-terminal portion of 80K-H was not required for the interaction. Immunoprecipitates of endogenous PKCζ from Cho cells, 3T3-L1 adipocytes or L6 myotubes contained endogenous 80K-H, demonstrating a physiological interaction. Insulin stimulation enhanced the association 3–5-fold. Immunoprecipitates of endogenous 80K-H contained endogenous munc18c and immunoprecipitates of endogenous munc18c contained endogenous PKCζ, with insulin markedly increasing the amount of co-immunoprecipitated protein in each case. These results show that insulin triggers interactions in vivo between PKCζ, 80K-H and munc18c. Overexpression of 80K-H constructs mimicked the action of insulin in stimulating both glucose uptake and translocation of Myc-tagged GLUT4 in Cho cells, with the level of effect proportional to the ability of the constructs to associate with munc18c. These results identify 80K-H as a new player involved in GLUT4 vesicle transport and identify a link between a kinase involved in the insulin signalling cascade, PKCζ, and a known component of the GLUT4 vesicle trafficking pathway, munc18c. The results suggest a model whereby insulin triggers the formation of a PKCζ–80K-H–munc18c complex that enhances GLUT4 translocation to the plasma membrane. PMID:15707389
Kracker, Sven; Di Virgilio, Michela; Schwartzentruber, Jeremy; Cuenin, Cyrille; Forveille, Monique; Deau, Marie-Céline; McBride, Kevin M.; Majewski, Jacek; Gazumyan, Anna; Seneviratne, Suranjith; Grimbacher, Bodo; Kutukculer, Necil; Herceg, Zdenko; Cavazzana, Marina; Jabado, Nada; Nussenzweig, Michel C.; Fischer, Alain; Durandy, Anne
2015-01-01
Background Immunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level. Objective This study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR). Methods Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR. Results We identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity. Conclusion INO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis. PMID:25312759
Handoffs in care--can we make them safer?
Streitenberger, Kim; Breen-Reid, Karen; Harris, Cheryl
2006-12-01
In today's complex and rapidly changing health care environments, patient harm may result if important patient information is not communicated from one health care provider to another during handoffs in care. Issues involving communication, continuity of care, and care planning are cited as a root cause in more than 80% of reported sentinel events. In light of the inherent risks associated with handoffs in care, the use of strategies that reduce the impact of human factors on effective communication and standardize the communication process is essential to ensure appropriate communication patient information and that a plan of care is continued through the process.
Ishizaki, H; Wheat, R W; Kiel, D P; Conant, N F
1978-01-01
Ethanol-precipitable culture filtrate antigens of 100 strains of 75 species of the Sporothrix-Ceratocystis-Europhium-Graphium complex and 1 species of Botrytis were examined for neutral sugar components and for serological cross-reactivity with S. schenckii rabbit antiserum and human sporotrichosis sera by capillary precipitin and double immunodiffusion assay. Results revealed that cross-reactive species (60 of 77, ca. 80%) produced exoconidial forms and rhamnose- and mannose-containing polysaccharides and included Ceratocystis, the three known Europhium, and several Graphium-form species. Endoconidial-form Ceratocystis species did not cross-react. Images PMID:99369
Zhou, Coral Y; Johnson, Stephanie L; Lee, Laura J; Longhurst, Adam D; Beckwith, Sean L; Johnson, Matthew J; Morrison, Ashby J; Narlikar, Geeta J
2018-02-15
The yeast INO80 chromatin remodeling complex plays essential roles in regulating DNA damage repair, replication, and promoter architecture. INO80's role in these processes is likely related to its ability to slide nucleosomes, but the underlying mechanism is poorly understood. Here we use ensemble and single-molecule enzymology to study INO80-catalyzed nucleosome sliding. We find that the rate of nucleosome sliding by INO80 increases ∼100-fold when the flanking DNA length is increased from 40 to 60 bp. Furthermore, once sliding is initiated, INO80 moves the nucleosome rapidly at least 20 bp without pausing to re-assess flanking DNA length, and it can change the direction of nucleosome sliding without dissociation. Finally, we show that the Nhp10 module of INO80 plays an auto-inhibitory role, tuning INO80's switch-like response to flanking DNA. Our results indicate that INO80 is a highly processive remodeling motor that is tightly regulated by both substrate cues and non-catalytic subunits. Copyright © 2018 Elsevier Inc. All rights reserved.
Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong
2011-01-01
Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457
Minyaev, Mikhail E; Tavtorkin, Alexander N; Korchagina, Sof'ya A; Bondarenko, Galina N; Churakov, Andrei V; Nifant'ev, Ilya E
2018-05-01
Crystals of mononuclear tris[bis(2,6-diisopropylphenyl) phosphato-κO]pentakis(methanol-κO)lanthanide methanol monosolvates of lanthanum, [La(C 24 H 34 O 4 P) 3 (CH 3 OH) 5 ]·CH 3 OH, (1), cerium, [Ce(C 24 H 34 O 4 P) 3 (CH 3 OH) 5 ]·CH 3 OH, (2), and neodymium, [Nd(C 24 H 34 O 4 P) 3 (CH 3 OH) 5 ]·CH 3 OH, (3), have been obtained by reactions between LnCl 3 (H 2 O) n (n = 6 or 7) and lithium bis(2,6-diisopropylphenyl) phosphate in a 1:3 molar ratio in methanol media. Compounds (1)-(3) crystallize in the monoclinic P2 1 /c space group and have isomorphous crystal structures. All three bis(2,6-diisopropylphenyl) phosphate ligands display a κO-monodentate coordination mode. The coordination number of the metal atom is 8. Each [Ln{O 2 P(O-2,6- i Pr 2 C 6 H 3 ) 2 } 3 (CH 3 OH) 5 ] molecular unit exhibits four intramolecular O-H...O hydrogen bonds, forming six-membered rings. The unit forms two intermolecular O-H...O hydrogen bonds with one noncoordinating methanol molecule. All six hydroxy H atoms are involved in hydrogen bonding within the [Ln{O 2 P(O-2,6- i Pr 2 C 6 H 3 ) 2 } 3 (CH 3 OH) 5 ]·CH 3 OH unit. This, along with the high steric hindrance induced by the three bulky diaryl phosphate ligands, prevents the formation of a hydrogen-bond network. Complexes (1)-(3) exhibit disorder of two of the isopropyl groups of the phosphate ligands. The cerium compound (2) demonstrates an essential catalytic inhibition in the thermal decomposition of polydimethylsiloxane in air at 573 K. Catalytic systems based on the neodymium complex tris[bis(2,6-diisopropylphenyl) phosphato-κO]neodymium, (3'), which was obtained as a dry powder of (3) upon removal of methanol, display a high catalytic activity in isoprene and butadiene polymerization.
40 CFR 80.65 - General requirements for refiners and importers.
Code of Federal Regulations, 2014 CFR
2014-07-01
... emissions performance in the case of gasoline certified using the complex model. (C) Benzene content; and (D) In the case of VOC-controlled gasoline or RBOB certified using the complex model, VOC emissions... calculate an emissions performance that the gasoline or RBOB is subject to, under § 80.41(a) through (f). (2...
NASA Astrophysics Data System (ADS)
Rodgers, Allen L.; Jackson, Graham E.
2017-04-01
Chondroitin sulfate (CS) occurs in human urine. It has several potential binding sites for calcium and as such may play an inhibitory role in calcium oxalate and calcium phosphate (kidney stone disease by reducing the supersaturation (SS) and crystallization of these salts. Urinary magnesium is also a role player in determining speciation in stone forming processes. This study was undertaken to determine the thermodynamic parameters for binding of the disaccharide unit of two different CS isomers with calcium and magnesium. These included the binding constant K. Experiments were performed using an isothermal titration calorimeter (ITC) at 3 different pH levels in the physiological range in human urine. Data showed that interactions between the CS isomers and calcium and magnesium occur via one binding site, thought to be sulfate, and that log K values are 1.17-1.93 and 1.77-1.80 for these two metals respectively. Binding was significantly stronger in Mg-CS than in Ca-CS complexes and was found to be dependent on pH in the latter but not in the former. Furthermore, binding in Ca-CS complexes was dependent on the location of the sulfate binding site. This was not the case in the Mg-CS complexes. Interactions were shown to be entropy driven and enthalpy unfavourable. These findings can be used in computational modeling studies to predict the effects of the calcium and magnesium CS complexes on the speciation of calcium and the SS of calcium salts in real urine samples.
Hieb, Aaron R; Halsey, Wayne A; Betterton, Meredith D; Perkins, Thomas T; Kugel, Jennifer F; Goodrich, James A
2007-09-21
Eukaryotic mRNA transcription by RNA polymerase II is a highly regulated complex reaction involving numerous proteins. In order to control tissue and promoter specific gene expression, transcription factors must work in concert with each other and with the promoter DNA to form the proper architecture to activate the gene of interest. The TATA binding protein (TBP) binds to TATA boxes in core promoters and bends the TATA DNA. We have used quantitative solution fluorescence resonance energy transfer (FRET) and gel-based FRET (gelFRET) to determine the effect of TFIIA on the conformation of the DNA in TBP/TATA complexes and on the kinetic stability of these complexes. Our results indicate that human TFIIA decreases the angle to which human TBP bends consensus TATA DNA from 104 degrees to 80 degrees when calculated using a two-kink model. The kinetic stability of TBP/TATA complexes was greatly reduced by increasing the KCl concentration from 50 mM to 140 mM, which is more physiologically relevant. TFIIA significantly enhanced the kinetic stability of TBP/TATA complexes, thereby attenuating the effect of higher salt concentrations. We also found that TBP bent non-consensus TATA DNA to a lesser degree than consensus TATA DNA and complexes between TBP and a non-consensus TATA box were kinetically unstable even at 50 mM KCl. Interestingly, TFIIA increased the calculated bend angle and kinetic stability of complexes on a non-consensus TATA box, making them similar to those on a consensus TATA box. Our data show that TFIIA induces a conformational change within the TBP/TATA complex that enhances its stability under both in vitro and physiological salt conditions. Furthermore, we present a refined model for the effect that TFIIA has on DNA conformation that takes into account potential changes in bend angle as well as twist angle.
Kim, Soo-Jin; Kim, Hyung Kwoun
2016-05-01
An organic solvent-stable lipase from Proteus vulgaris K80 was used to produce the omega-3 polyunsaturated fatty acid ethyl esters (ω-3 PUFA EEs). First, the lyophilized recombinant lipase K80 (LyoK80) was used to perform the transesterification reaction of menhaden oil and ethanol. LyoK80 produced the ω-3 PUFA EEs with a conversion yield of 82 % in the presence of 20 % water content via a three-step ethanol-feeding process; however, in a non-aqueous condition, LyoK80 produced only a slight amount of the ω-3 PUFA EEs. To enhance its reaction properties, the lipase K80 was immobilized on a hydrophobic bead to derive ImmK80; the biochemical properties and substrate specificity of ImmK80 are similar to those of LyoK80. ImmK80 was then used to produce ω-3 PUFA EEs in accordance with the same transesterification reaction. Unlike LyoK80, ImmK80 achieved a high ω-3 PUFA EE conversion yield of 86 % under a non-aqueous system via a one-step ethanol-feeding reaction. The ω-3 PUFA EEs were purified up to 92 % using a urea complexation method.
Salouti, Mojtaba; Babaei, Mohammad Hossein; Rajabi, Hossein; Rasaee, Mohammad javad
2011-08-01
PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. The radiochemical purity and in vitro stability of (177)Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. The radiochemical purity was 91.2±3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1±3.4% and 76.2±3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4±2.4%. The cell toxicity study showed that the complex inhibited 85.2±3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. The results showed that one may consider (177)Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations. Copyright © 2011 Elsevier Inc. All rights reserved.
Structure of palmitoylated BET3: insights into TRAPP complex assembly and membrane localization
Turnbull, Andrew P; Kümmel, Daniel; Prinz, Bianka; Holz, Caterina; Schultchen, Jeffrey; Lang, Christine; Niesen, Frank H; Hofmann, Klaus-Peter; Delbrück, Heinrich; Behlke, Joachim; Müller, Eva-Christina; Jarosch, Ernst; Sommer, Thomas; Heinemann, Udo
2005-01-01
BET3 is a component of TRAPP, a complex involved in the tethering of transport vesicles to the cis-Golgi membrane. The crystal structure of human BET3 has been determined to 1.55-Å resolution. BET3 adopts an α/β-plait fold and forms dimers in the crystal and in solution, which predetermines the architecture of TRAPP where subunits are present in equimolar stoichiometry. A hydrophobic pocket within BET3 buries a palmitate bound through a thioester linkage to cysteine 68. BET3 and yeast Bet3p are palmitoylated in recombinant yeast cells, the mutant proteins BET3 C68S and Bet3p C80S remain unmodified. Both BET3 and BET3 C68S are found in membrane and cytosolic fractions of these cells; in membrane extractions, they behave like tightly membrane-associated proteins. In a deletion strain, both Bet3p and Bet3p C80S rescue cell viability. Thus, palmitoylation is neither required for viability nor sufficient for membrane association of BET3, which may depend on protein–protein contacts within TRAPP or additional, yet unidentified modifications of BET3. A conformational change may facilitate palmitoyl extrusion from BET3 and allow the fatty acid chain to engage in intermolecular hydrophobic interactions. PMID:15692564
21 CFR 80.35 - Color additive mixtures; certification and exemption from certification.
Code of Federal Regulations, 2011 CFR
2011-04-01
... certified if intended for use in foods, drugs, or cosmetics, or in coloring the human body, as the case may... cosmetics which color the human body, 29 FR 18495, Dec. 29, 1964. ... HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE CERTIFICATION Certification Procedures § 80.35 Color...
21 CFR 80.35 - Color additive mixtures; certification and exemption from certification.
Code of Federal Regulations, 2010 CFR
2010-04-01
... certified if intended for use in foods, drugs, or cosmetics, or in coloring the human body, as the case may... cosmetics which color the human body, 29 FR 18495, Dec. 29, 1964. ... HEALTH AND HUMAN SERVICES GENERAL COLOR ADDITIVE CERTIFICATION Certification Procedures § 80.35 Color...
Cai, Wenjia; Hui, Jingxuan; Wang, Can; Zheng, Yixuan; Zhang, Xin; Zhang, Qiang; Gong, Peng
2018-04-01
Except for comparing the implementation costs of the Paris Agreement with potential health benefits at the national levels, previous studies have not explored the health impacts of the nationally determined contributions (NDCs) by countries and in regional details. In this Lancet Countdown study, we aimed to estimate and monetise the health benefits of China's NDCs in the electric power generation sector, and then compare them with the implementation costs, both at the national and regional levels. In this modelling study, we linked the Multi-regional model for Energy Supply system and their Environmental ImpaCts, the Multi-resolution Emission Inventory for China model, the offline-coupled Weather Research and Forecasting model, the Community Multiscale Air Quality model, and the Integrated Health Impact Assessment model with a time scope from 2010 to 2050. We calculated the PM 2·5 concentrations and compared the health impacts and implementation costs between two scenarios that reflect CO 2 and air pollutant emissions-the reference (REF) scenario (no climate policy) and the NDC scenario (100% realisation of NDC targets: CO 2 emission intensity needs to be about 40% below 2010 emissions by 2030 [roughly 35% below 2030 emissions in REF], and about 90% below 2010 emissions by 2050 [roughly 96% below 2050 emissions in REF]). Under a comparatively optimistic health benefits valuation condition, at the national level, 18-62% of implementation costs could be covered by the health benefits in 2030. In 2050, the overall health benefits would substantially increase to 3-9 times of the implementation costs. However, northwest China would require the highest implementation costs and will also have more premature deaths because of a more carbon-intensive energy structure than business as usual. By 2030, people in northwest China (especially in Gansu, Shaanxi, and Xinjiang provinces) would need to bear worse air quality, and 10 083 (95% CI 3419-16 138) more premature deaths annually. This undesirable situation would diminish by about 2050. A solution that assumes no growth in air pollutant emissions in 2030 at the regional level is technically feasible, but would not be cost-effective. Our results suggest that cost-benefit analysis of climate policy that omits regional air pollution could greatly underestimate benefits. A compensation mechanism for inter-regional interests (including financial, technological, and knowledge support) should be established for regions that give up their human health benefits for the sake of the whole nation to realise the climate change targets. National Natural Science Foundation of China and Cyrus Tang Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.
Kracker, Sven; Di Virgilio, Michela; Schwartzentruber, Jeremy; Cuenin, Cyrille; Forveille, Monique; Deau, Marie-Céline; McBride, Kevin M; Majewski, Jacek; Gazumyan, Anna; Seneviratne, Suranjith; Grimbacher, Bodo; Kutukculer, Necil; Herceg, Zdenko; Cavazzana, Marina; Jabado, Nada; Nussenzweig, Michel C; Fischer, Alain; Durandy, Anne
2015-04-01
Immunoglobulin class-switch recombination defects (CSR-D) are rare primary immunodeficiencies characterized by impaired production of switched immunoglobulin isotypes and normal or elevated IgM levels. They are caused by impaired T:B cooperation or intrinsic B cell defects. However, many immunoglobulin CSR-Ds are still undefined at the molecular level. This study's objective was to delineate new causes of immunoglobulin CSR-Ds and thus gain further insights into the process of immunoglobulin class-switch recombination (CSR). Exome sequencing in 2 immunoglobulin CSR-D patients identified variations in the INO80 gene. Functional experiments were performed to assess the function of INO80 on immunoglobulin CSR. We identified recessive, nonsynonymous coding variations in the INO80 gene in 2 patients affected by defective immunoglobulin CSR. Expression of wild-type INO80 in patients' fibroblastic cells corrected their hypersensitivity to high doses of γ-irradiation. In murine CH12-F3 cells, the INO80 complex accumulates at Sα and Eμ regions of the IgH locus, and downregulation of INO80 as well as its partners Reptin and Pontin impaired CSR. In addition, Reptin and Pontin were shown to interact with activation-induced cytidine deaminase. Finally, an abnormal separation of sister chromatids was observed upon INO80 downregulation in CH12-F3 cells, pinpointing its role in cohesin activity. INO80 deficiency appears to be associated with defective immunoglobulin CSR. We propose that the INO80 complex modulates cohesin function that may be required during immunoglobulin switch region synapsis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.
Heyma, P; Harrison, L C
1984-01-01
The thyrotropin (TSH) receptor is a putative target for autoantibodies in Graves' hyperthyroidism and therefore, should be capable of being identified, isolated, and structurally characterized by immunological means. To this end, four sera from patients with hyperthyroidism, three of which inhibited the binding of 125I-TSH to Triton-solubilized human thyroid membranes, were used to isolate TSH receptors by immunoprecipitation. To account for an effect of TSH binding or receptor occupancy on the ability of Graves' immunoglobulins to precipitate TSH receptors, two approaches were taken: (a) specific 125I-TSH binding activity was measured after solubilized thyroid membranes had been incubated with Graves' sera followed by precipitation with Staphylococcus protein A ("receptor depletion"); (b) TSH binding sites were labeled with 125I-TSH and the complexes were precipitated using Graves' sera and Staphylococcus protein A ("receptor precipitation"). The three sera which inhibited 125I-TSH binding depleted 125I-TSH binding activity between 30-80%. Preformed complexes between Staphylococcus protein A and immunoglobulins in these sera were also able to deplete 125I-TSH binding activity. However, after receptor depletion, the one serum that did not inhibit 125I-TSH binding was associated with a significant increase in 125I-TSH binding. All four sera specifically precipitated 80-100% of receptors identified by prelabeling with 125I-TSH. The dilutions of sera that precipitated 50% of 125I-TSH-receptor complexes ranged from 1:150-1:20. Complexes were partially precipitated by high concentrations of control sera (1:20), but the relative potency of control sera was at least fourfold less than Graves' sera. Immunoprecipitates of 125I-labeled thyroid membranes were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography to reveal Graves'-specific bands of reduced molecular weights of 100-110,000, 80-90,000, and 70-75,000. These bands were similar to those obtained from 125I-labeled thyroid membranes purified by TSH affinity chromatography. Thus, Graves' immunoglobulins: (a) precipitate unoccupied and occupied TSH receptors, (b) in one case, neither inhibit binding nor immunodeplete the unoccupied receptor but immunoprecipitate 125I-TSH-receptor complexes, suggesting that binding of TSH may initiate an interaction between the binding site and a separate immunoreactive molecule, and (c) identify the molecular structure of Graves' autoantigens, putatively, the TSH receptor. Images PMID:6088581
Differential association of protein subunits with the human RNase MRP and RNase P complexes.
Welting, Tim J M; Kikkert, Bastiaan J; van Venrooij, Walther J; Pruijn, Ger J M
2006-07-01
RNase MRP is a eukaryotic endoribonuclease involved in nucleolar and mitochondrial RNA processing events. RNase MRP is a ribonucleoprotein particle, which is structurally related to RNase P, an endoribonuclease involved in pre-tRNA processing. Most of the protein components of RNase MRP have been reported to be associated with RNase P as well. In this study we determined the association of these protein subunits with the human RNase MRP and RNase P particles by glycerol gradient sedimentation and coimmunoprecipitation. In agreement with previous studies, RNase MRP sedimented at 12S and 60-80S. In contrast, only a single major peak was observed for RNase P at 12S. The analysis of individual protein subunits revealed that hPop4 (also known as Rpp29), Rpp21, Rpp20, and Rpp25 only sedimented in 12S fractions, whereas hPop1, Rpp40, Rpp38, and Rpp30 were also found in 60-80S fractions. In agreement with their cosedimentation with RNase P RNA in the 12S peak, coimmunoprecipitation with VSV-epitope-tagged protein subunits revealed that hPop4, Rpp21, and in addition Rpp14 preferentially associate with RNase P. These data show that hPop4, Rpp21, and Rpp14 may not be associated with RNase MRP. Furthermore, Rpp20 and Rpp25 appear to be associated with only a subset of RNase MRP particles, in contrast to hPop1, Rpp40, Rpp38, and Rpp30 (and possibly also hPop5), which are probably associated with all RNase MRP complexes. Our data are consistent with a transient association of Rpp20 and Rpp25 with RNase MRP, which may be inversely correlated to its involvement in pre-rRNA processing.
An Evaluation of North Korea’s Nuclear Test by Belbasi Nuclear Tests Monitoring Center-KOERI
NASA Astrophysics Data System (ADS)
Necmioglu, O.; Meral Ozel, N.; Semin, K.
2009-12-01
Bogazici University and Kandilli Observatory and Earthquake Research Institute (KOERI) is acting as the Turkish National Data Center (NDC) and responsible for the operation of the International Monitoring System (IMS) Primary Seismic Station (PS-43) under Belbasi Nuclear Tests Monitoring Center for the verification of compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT) since February 2000. The NDC is responsible for operating two arrays which are part of the IMS, as well as for transmitting data from these stations to the International Data Centre (IDC) in Vienna. The Belbasi array was established in 1951, as a four-element (Benioff 1051) seismic array as part of the United States Atomic Energy Detection System (USAEDS). Turkish General Staff (TGS) and U.S. Air Force Technical Application Center (AFTAC) under the Defense and Economic Cooperation Agreement (DECA) jointly operated this short period array. The station was upgraded and several seismometers were added to array during 1951 and 1994 and the station code was changed from BSRS (Belbasi Seismic Research Station) to BRTR-PS43 later on. PS-43 is composed of two sub-arrays (Ankara and Keskin): the medium-period array with a ~40 km radius located in Ankara and the short-period array with a ~3 km radius located in Keskin. Each array has a broadband element located at the middle of the circular geometry. Short period instruments are installed at depth 30 meters from the surface while medium and broadband instruments are installed at depth 60 meters from surface. On 25 May 2009, The Democratic People’s Republic of Korea (DPRK) claimed that it had conducted a nuclear test. Corresponding seismic event was recorded by IMS and IDC released first automatic estimation of time (00:54:43 GMT), location (41.2896°N and 129.0480°E) and the magnitude (4.52 mb) of the event in less than two hours time (USGS: 00:54:43 GMT; 41.306°N, 129.029°E; 4.7 mb) During our preliminary analysis of the 25th May 2009 DPRK event, we saw a very clear P arrival at 01:05:47 (GMT) at BRTR SP array. The result of the f-k analysis performed in Geotool software, installed at NDC facilities in 2008 and is in full use currently, was also indicating that the arrival belongs to the DPRK event. When comparing our f-k results (calculated at 1-2 Hz) with IDC-REB, however, we have noticed that our calculation and therefore corresponding residuals (calculated with reference to REB residuals) are much better in comparison to REB. The reasons of this ambiguity have been explored and for the first time a comprehensive seismological analysis of a Nuclear Test has been conducted in Turkey. CTBT has an important role for the implementation of the non-proliferation of nuclear weapons and it is a key element for the pursuit of nuclear disarmament. In this study, we would like to reflect the technical and scientific aspects of the 25 May 2009 DPRK event analysis, together with our involvement in CTBT(O) affairs, which we believe it brings new dimensions to Turkey especially in the area of Geophysics.
Self-Reliability and Motivation in a Nuclear Security Culture Enhancement Program
DOE Office of Scientific and Technical Information (OSTI.GOV)
Crawford, Cary E.; de Boer, Gloria; De Castro, Kara
2010-10-01
The threat of nuclear terrorism has become a global concern. Many countries continue to make efforts to strengthen nuclear security by enhancing systems of nuclear material protection, control, and accounting (MPC&A). Though MPC&A systems can significantly upgrade nuclear security, they do not eliminate the “human factor.” Gen. Eugene Habiger, a former “Assistant Secretary for Safeguards and Security” at the U.S. Department of Energy’s (DOE) nuclear-weapons complex and a former commander of U.S. strategic nuclear forces, has observed that “good security is 20% equipment and 80% people.”1 Although eliminating the “human factor” is not possible, accounting for and mitigating the riskmore » of the insider threat is an essential element in establishing an effective nuclear security culture. This paper will consider the organizational role in mitigating the risk associated with the malicious insider through monitoring and enhancing human reliability and motivation as well as enhancing the nuclear security culture.« less
Self-Reliability and Motivation in a Nuclear Security Culture Enhancement Program
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rogers,E.; deBoer,G.; Crawford, C.
2009-10-19
The threat of nuclear terrorism has become a global concern. Many countries continue to make efforts to strengthen nuclear security by enhancing systems of nuclear material protection, control, and accounting (MPC&A). Though MPC&A systems can significantly upgrade nuclear security, they do not eliminate the "human factor." Gen. Eugene Habiger, a former "Assistant Secretary for Safeguards and Security" at the U.S. Department of Energy’s (DOE) nuclear-weapons complex and a former commander of U.S. strategic nuclear forces, has observed that "good security is 20% equipment and 80% people." Although eliminating the "human factor" is not possible, accounting for and mitigating the riskmore » of the insider threat is an essential element in establishing an effective nuclear security culture. This paper will consider the organizational role in mitigating the risk associated with the malicious insider through monitoring and enhancing human reliability and motivation as well as enhancing the nuclear security culture.« less
Khaĭrulina, Iu S; Molotkov, M V; Bulygin, K N; Graĭfer, D M; Ven'iaminova, A G; Karpova, G G
2008-01-01
Protein S15 is a characteristic component of the mammalian 80S ribosome that neighbors mRNA codon at the decoding site and the downstream triplets. In this study we determined S15 protein fragments located close to mRNA positions +4 to +12 with respect to the first nucleotide of the P site codon on the human ribosome. For cross-linking to ribosomal protein S15, a set of mRNA was used that contained triplet UUU/UUC at the 5'-termini and a perfluorophenyl azide-modified uridine in position 3' of this triplet. The locations of mRNA analogues on the ribosome were governed by tRNAPhe cognate to the UUU/UUC triplet targeted to the P site. Cross-linked S15 protein was isolated from the irradiated with mild UV light complexes of 80S ribosomes with tRNAPhe and mRNA analogues with subsequent cleavage with CNBr that splits polypeptide chain after methionines. Analysis of modified oligopeptides resulted from the cleavage revealed that in all cases cross-linking site was located in C-terminal fragment 111-145 of protein S15 indicating that this fragment is involved in formation of decoding site of the eukaryotic ribosome.
Kim, Kyoung Mi; Cho, Hana; Choi, Kobong; Kim, Jaedong; Kim, Bong-Woo; Ko, Young-Gyu; Jang, Sung Key; Kim, Yoon Ki
2009-01-01
During or right after mRNA export via the nuclear pore complex (NPC) in mammalian cells, mRNAs undergo translation mediated by nuclear cap-binding proteins 80 and 20 (CBP80/20). After CBP80/20-dependent translation, CBP80/20 is replaced by cytoplasmic cap-binding protein eIF4E, which directs steady-state translation. Nonsense-mediated mRNA decay (NMD), one of the best-characterized mRNA surveillance mechanisms, has been shown to occur on CBP80/20-bound mRNAs. However, despite the tight link between CBP80/20-dependent translation and NMD, the underlying molecular mechanism and cellular factors that mediate CBP80/20-dependent translation remain obscure. Here, we identify a new MIF4G domain-containing protein, CTIF (CBP80/20-dependent translation initiation factor). CTIF interacts directly with CBP80 and is part of the CBP80/20-dependent translation initiation complex. Depletion of endogenous CTIF from an in vitro translation system selectively blocks the translation of CBP80-bound mRNAs, while addition of purified CTIF restores it. Accordingly, down-regulation of endogenous CTIF abrogates NMD. Confocal microscopy shows that CTIF is localized to the perinuclear region. Our observations demonstrate the existence of CBP80/20-dependent translation and support the idea that CBP80/20-dependent translation is mechanistically different from steady-state translation through identification of a specific cellular protein, CTIF. PMID:19648179
Choe, Junho; Oh, Nara; Park, Sungjin; Lee, Ye Kyung; Song, Ok-Kyu; Locker, Nicolas; Chi, Sung-Gil; Kim, Yoon Ki
2012-05-25
In the cytoplasm of mammalian cells, either cap-binding proteins 80 and 20 (CBP80/20) or eukaryotic translation initiation factor (eIF) 4E can direct the initiation of translation. Although the recruitment of ribosomes to mRNAs during eIF4E-dependent translation (ET) is well characterized, the molecular mechanism for CBP80/20-dependent translation (CT) remains obscure. Here, we show that CBP80/20-dependent translation initiation factor (CTIF), which has been shown to be preferentially involved in CT but not ET, specifically interacts with eIF3g, a component of the eIF3 complex involved in ribosome recruitment. By interacting with eIF3g, CTIF serves as an adaptor protein to bridge the CBP80/20 and the eIF3 complex, leading to efficient ribosome recruitment during CT. Accordingly, down-regulation of CTIF using a small interfering RNA causes a redistribution of CBP80 from polysome fractions to subpolysome fractions, without significant consequence to eIF4E distribution. In addition, down-regulation of eIF3g inhibits the efficiency of nonsense-mediated mRNA decay, which is tightly coupled to CT but not to ET. Moreover, the artificial tethering of CTIF to an intercistronic region of dicistronic mRNA results in translation of the downstream cistron in an eIF3-dependent manner. These findings support the idea that CT mechanistically differs from ET.
NASA Technical Reports Server (NTRS)
Aoyagi, Kiyoshi; Olson, Lawrence E.; Peterson, Randall L.; Yamauchi, Gloria K.; Ross, James C.; Norman, Thomas R.
1987-01-01
Time-averaged aerodynamic loads are estimated for each of the vane sets in the National Full-Scale Aerodynamic Complex (NFAC). The methods used to compute global and local loads are presented. Experimental inputs used to calculate these loads are based primarily on data obtained from tests conducted in the NFAC 1/10-Scale Vane-Set Test Facility and from tests conducted in the NFAC 1/50-Scale Facility. For those vane sets located directly downstream of either the 40- by 80-ft test section or the 80- by 120-ft test section, aerodynamic loads caused by the impingement of model-generated wake vortices and model-generated jet and propeller wakes are also estimated.
Williams, Gareth J.; Hammel, Michal; Radhakrishnan, Sarvan Kumar; Ramsden, Dale; Lees-Miller, Susan P.; Tainer, John A.
2014-01-01
Non-homologous end joining (NHEJ) is the major pathway for repair of DNA double-strand breaks (DSBs) in human cells. NHEJ is also needed for V(D)J recombination and the development of T and B cells in vertebrate immune systems, and acts in both the generation and prevention of non-homologous chromosomal translocations, a hallmark of genomic instability and many human cancers. X-ray crystal structures, cryo-electron microscopy envelopes, and small angle X-ray scattering (SAXS) solution conformations and assemblies are defining most of the core protein components for NHEJ: Ku70/Ku80 heterodimer; the DNA dependent protein kinase catalytic subunit (DNA-PKcs); the structure-specific endonuclease Artemis along with polynucleotide kinase/phosphatase (PNKP), aprataxin and PNKP related protein (APLF); the scaffolding proteins XRCC4 and XLF (XRCC4-like factor); DNA polymerases, and DNA ligase IV (Lig IV). The dynamic assembly of multi-protein NHEJ complexes at DSBs is regulated in part by protein phosphorylation. The basic steps of NHEJ have been biochemically defined to require: 1) DSB detection by the Ku heterodimer with subsequent DNA-PKcs tethering to form the DNA-PKcs-Ku-DNA complex (termed DNA-PK), 2) lesion processing, and 3) DNA end ligation by Lig IV, which functions in complex with XRCC4 and XLF. The current integration of structures by combined methods is resolving puzzles regarding the mechanisms, coordination and regulation of these three basic steps. Overall, structural results suggest the NHEJ system forms a flexing scaffold with the DNA-PKcs HEAT repeats acting as compressible macromolecular springs suitable to store and release conformational energy to apply forces to regulate NHEJ complexes and the DNA substrate for DNA end protection, processing, and ligation. PMID:24656613
First U.S. near-total human face transplantation: a paradigm shift for massive complex injuries.
Siemionow, Maria Z; Papay, Frank; Djohan, Risal; Bernard, Steven; Gordon, Chad R; Alam, Daniel; Hendrickson, Mark; Lohman, Robert; Eghtesad, Bijan; Fung, John
2010-01-01
Severe complex facial injuries are difficult to reconstruct and require multiple surgical procedures. The potential of performing complex craniofacial reconstruction in one surgical procedure is appealing, and composite face allograft transplantation may be considered an alternative option. The authors describe establishment of the Cleveland Clinic face transplantation program that led them to perform the first U.S. near-total face transplantation. In November of 2004, the authors received the world's first institutional review board approval to perform a face transplant in humans. In December of 2008, after a 22-hour operation, the authors performed the first near-total face transplantation in the United States, replacing 80 percent of the patient's traumatic facial deficit with a composite allograft from a brain-dead donor. This largest, and most complex, face allograft in the world included over 535 cm2 of facial skin; functional units of full nose with nasal lining and bony skeleton; lower eyelids and upper lip; underlying muscles and bones, including orbital floor, zygoma, maxilla, alveolus with teeth, hard palate, and parotid glands; and pertinent nerves, arteries, and veins. Immunosuppressive treatment consisted of thymoglobulin, tacrolimus, mycophenolate mofetil, and prednisone. The patient tolerated the procedure and immunosuppression well. At day 47 after transplantation, routine biopsy showed rejection of the graft mucosa without clinical evidence of skin or graft rejection. The patient's physical and psychological recovery went well. The functional outcome has been excellent, including optimal return of breathing through the nose, smelling, tasting, speaking, drinking from a cup, and eating solid foods. The functional outcome thus far at 8 months is rewarding and confirms the feasibility of performing complex reconstruction of severely disfigured patients in a single surgical procedure of facial allotransplantation.
21 CFR 110.80 - Processes and controls.
Code of Federal Regulations, 2010 CFR
2010-04-01
... HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN MANUFACTURING, PACKING, OR HOLDING HUMAN FOOD Production and Process Controls § 110.80 Processes and controls. All operations in the receiving, inspecting, transporting, segregating, preparing, manufacturing, packaging, and storing of food shall be conducted in...
Origin and Evolution of European Community-Acquired Methicillin-Resistant Staphylococcus aureus
Wirth, Thierry; Andersen, Paal S.; Skov, Robert L.; De Grassi, Anna; Simões, Patricia Martins; Tristan, Anne; Petersen, Andreas; Aziz, Maliha; Kiil, Kristoffer; Cirković, Ivana; Udo, Edet E.; del Campo, Rosa; Vuopio-Varkila, Jaana; Ahmad, Norazah; Tokajian, Sima; Peters, Georg; Schaumburg, Frieder; Olsson-Liljequist, Barbro; Givskov, Michael; Driebe, Elizabeth E.; Vigh, Henrik E.; Shittu, Adebayo; Ramdani-Bougessa, Nadjia; Rasigade, Jean-Philippe; Price, Lance B.; Vandenesch, Francois; Larsen, Anders R.; Laurent, Frederic
2014-01-01
ABSTRACT Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. PMID:25161186
Basrai, M A; Kingsbury, J; Koshland, D; Spencer, F; Hieter, P
1996-01-01
A chromosome transmission fidelity (ctf) mutant, s138, of Saccharomyces cerevisiae was identified by its centromere (CEN) transcriptional readthrough phenotype, suggesting perturbed kinetochore integrity in vivo. The gene complementing the s138 mutation was found to be identical to the S. cerevisiae SPT4 gene. The s138 mutation is a missense mutation in the second of four conserved cysteine residues positioned similarly to those of zinc finger proteins, and we henceforth refer to the mutation of spt4-138. Both spt4-138 and spt4 delta strains missegregate a chromosome fragment at the permissive temperature, are temperature sensitive for growth at 37 degrees C, and upon a shift to the nonpermissive temperature show an accumulation of large budded cells, each with a nucleus. Previous studies suggest that Spt4p functions in a complex with Spt5p and Spt6p, and we determined that spt6-140 also causes missegregation of a chromosome fragment. Double mutants carrying spt4 delta 2::HIS3 and kinetochore mutation ndc10-42 or ctf13-30 show a synthetic conditional phenotype. Both spt4-138 and spt4 delta strains exhibit synergistic chromosome instability in combination with CEN DNA mutations and show in vitro defects in microtubule binding to minichromosomes. These results indicate that Spt4p plays a role in chromosome segregation. The results of in vivo genetic interactions with mutations in kinetochore proteins and CEN DNA and of in vitro biochemical assays suggest that Spt4p is important for kinetochore function. PMID:8649393
DOE Office of Scientific and Technical Information (OSTI.GOV)
Saijo, Shinya; Sato, Takao; Kumasaka, Takashi
The reaction center–light-harvesting 1 core complex from R. viridis was crystallized and X-ray diffraction data were collected to 8.0 Å resolution. The reaction center–light-harvesting 1 (RC–LH1) core complex is the photosynthetic apparatus in the membrane of the purple photosynthetic bacterium Rhodopseudomonas viridis. The RC is surrounded by an LH1 complex that is constituted of oligomers of three types of apoproteins (α, β and γ chains) with associated bacteriochlorophyll bs and carotenoid. It has been crystallized by the sitting-drop vapour-diffusion method. A promising crystal diffracted to beyond 8.0 Å resolution. It belonged to space group P1, with unit-cell parameters a =more » 141.4, b = 136.9, c = 185.3 Å, α = 104.6, β = 94.0, γ = 110.7°. A Patterson function calculated using data between 15.0 and 8.0 Å resolution suggested that the LH1 complex is distributed with quasi-16-fold rotational symmetry around the RC.« less
Pérez-Arnaiz, Cristina; Busto, Natalia; Santolaya, Javier; Leal, José M; Barone, Giampaolo; García, Begoña
2018-03-01
Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in >80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. UV-Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na + or K + . T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K + buffer, "hybrid 1" conformation yields kinetic constants on interaction with TMPyP4 one order lower than "hybrid 2". The binding involves π-π stacking with external loop bases. For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable. G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules. Copyright © 2017 Elsevier B.V. All rights reserved.
Romanian Complex Data Center for Dense Seismic network
NASA Astrophysics Data System (ADS)
Neagoe, Cristian; Ionescu, Constantin; Marius Manea, Liviu
2010-05-01
Since 2002 the National Institute for Earth Physics (NIEP) developed its own real-time digital seismic network: consisting of 96 seismic stations of which 35 are broadband sensors and 24 stations equipped with short period sensors and two arrays earthquakes that transmit data in real time at the National Data Center (NDC) and Eforie Nord (EFOR) Seismic Observatory. EFOR is the back-up for the NDC and also a monitoring center for Black Sea tsunamis. Seismic stations are equipped with Quanterra Q330 and K2 digitizers, broadband seismometers (STS2, CMG40T, CMG 3ESP, CMG3T) and acceleration sensors Episensor Kinemetrics (+ / - 2G). SeedLink who is a part of Seiscomp2.5 and Antelope are software packages used for acquisition in real time (RT) and for data exchange. Communication of digital seismic stations to the National Data Center in Bucharest and Seismic Observatory Eforie Nord is assured by 5 providers (GPRS, VPN, satellite radio and Internet communication). For acquisition and data processing at the two centers of reception and processing is used AntelopeTM 4.11 running on 2 workstations: one for real-time and other for offline processing and also a Seiscomp 3 server that works as back-up for Antelope 4.11 Both acquisition and analysis of seismic data systems produced information about local and global parameters of earthquakes, in addition Antelope is used for manual processing (association events, the calculation of magnitude, creating a database, sending seismic bulletins, calculation of PGA and PGV , etc.), generating ShakeMap products and interacts with global data centers. In order to make all this information easily available across the Web and also lay the grounds for a more modular and flexible development environment the National Data Center developed tools to enable centralizing of data from software such as Antelope which is using a dedicated database system ( Datascope, a database system based on text files ) to a more general-purpose database, MySQL which acts like a hub between the different acquisition and analysis systems used in the data center while also providing better connectivity at no expense in security. Mirroring certain data to MySQL also allows the National Data Center to easily share information to the public via the new application which is being developed and also mix in data collected from the public (e.g. information about the damages observed after an earthquake which intern is being used to produce macroseismic intensity indices which are then stored in the database and also made available via the web application). For internal usage there is also a web application which using data stored in the database displays earthquake information like location, magnitude and depth in semi-real-time thus aiding the personnel on duty. Another usage for the collected data is to create and maintain contact lists to which the datacenter sends notifications (SMS and emails) based on the parameters of the earthquake. For future development, amongst others the Data Center plans to develop the means to crosscheck the generated data between the different acquisition and analysis systems (e.g. comparing data generated by Antelope with data generated by Seiscomp).
Effects of freezing on the bactericidal activity of human milk.
Takci, Sahin; Gulmez, Dolunay; Yigit, Sule; Dogan, Ozlem; Dik, Kezban; Hascelik, Gulsen
2012-08-01
Storage of human milk by freezing has been recommended for long-term storage. The present study analyzed the bactericidal activity of human milk on Escherichia coli and Pseudomonas aeruginosa and determined the changes in bactericidal activity following freezing at -20°C and -80°C for 1 month and 3 months. Forty-eight milk samples were collected from 48 lactating mothers. Each sample was divided into 10 aliquots. Two of the samples were processed immediately and the others were stored at both -20°C and -80°C until analysis after 1 month and 3 months of freezing. All of the fresh milk samples showed bactericidal activity against E coli and P aeruginosa. Freezing at -20°C for 1 month did not cause statistically significant alteration in bactericidal activity (P > 0.017), whereas storage for 3 months lowered the degree of bactericidal activity significantly (P < 0.017) against E coli. Bactericidal activity was protected when the samples were stored at -80°C. There was no statistically significant difference in the bactericidal activity of human milk against E coli between freezing at -20°C and -80°C for 1 month (P > 0.017); however, when milk was stored for 3 months, -80°C was significantly more protective (P < 0.017). Freezing at -20°C and -80°C for 1 month and 3 months did not cause any significant change in bactericidal activity against P aeruginosa (P > 0.05). Storage by freezing at -80°C is more appropriate to keep bactericidal capacity of stored human milk >1 month if affordable and available, especially in intensive care settings.
The complex fabric of public opinion on space
NASA Astrophysics Data System (ADS)
A. Roy, Stephanie; C. Gresham, Elaine; Christensen, Carissa Bryce
2000-07-01
Survey questions can be useful tools in gauging public interest. An historical analysis of U.S. public opinion on space-related issues presents some valuable results. Space-related poll questions closely track major events in the history of the U.S. space program. Funding questions are consistently asked, although program-related questions are becoming increasingly popular. Support for space funding has remained remarkably stable at approximately 80% since 1965, with only one significant dip in support in the early 1970s. However, responses on funding questions are extremely sensitive to question wording and should be used cautiously. Around 75% of the American public generally approve of the job that NASA is doing. Human space flight wins out over robotic space programs when put head-to-head, although support for a human Mars mission is on the decline. Despite dramatic increases in commercial space activities, in general opinion polls fail to reflect this increasingly dominant sector of the space economy.
Discrete domains of gene expression in germinal layers distinguish the development of gyrencephaly
de Juan Romero, Camino; Bruder, Carl; Tomasello, Ugo; Sanz-Anquela, José Miguel; Borrell, Víctor
2015-01-01
Gyrencephalic species develop folds in the cerebral cortex in a stereotypic manner, but the genetic mechanisms underlying this patterning process are unknown. We present a large-scale transcriptomic analysis of individual germinal layers in the developing cortex of the gyrencephalic ferret, comparing between regions prospective of fold and fissure. We find unique transcriptional signatures in each germinal compartment, where thousands of genes are differentially expressed between regions, including ∼80% of genes mutated in human cortical malformations. These regional differences emerge from the existence of discrete domains of gene expression, which occur at multiple locations across the developing cortex of ferret and human, but not the lissencephalic mouse. Complex expression patterns emerge late during development and map the eventual location of folds or fissures. Protomaps of gene expression within germinal layers may contribute to define cortical folds or functional areas, but our findings demonstrate that they distinguish the development of gyrencephalic cortices. PMID:25916825
Fuchs, Gabriele; Petrov, Alexey N; Marceau, Caleb D; Popov, Lauren M; Chen, Jin; O'Leary, Seán E; Wang, Richard; Carette, Jan E; Sarnow, Peter; Puglisi, Joseph D
2015-01-13
Translation initiation can occur by multiple pathways. To delineate these pathways by single-molecule methods, fluorescently labeled ribosomal subunits are required. Here, we labeled human 40S ribosomal subunits with a fluorescent SNAP-tag at ribosomal protein eS25 (RPS25). The resulting ribosomal subunits could be specifically labeled in living cells and in vitro. Using single-molecule Förster resonance energy transfer (FRET) between RPS25 and domain II of the hepatitis C virus (HCV) internal ribosome entry site (IRES), we measured the rates of 40S subunit arrival to the HCV IRES. Our data support a single-step model of HCV IRES recruitment to 40S subunits, irreversible on the initiation time scale. We furthermore demonstrated that after binding, the 40S:HCV IRES complex is conformationally dynamic, undergoing slow large-scale rearrangements. Addition of translation extracts suppresses these fluctuations, funneling the complex into a single conformation on the 80S assembly pathway. These findings show that 40S:HCV IRES complex formation is accompanied by dynamic conformational rearrangements that may be modulated by initiation factors.
Immobile defects in ferroelastic walls: Wall nucleation at defect sites
NASA Astrophysics Data System (ADS)
He, X.; Salje, E. K. H.; Ding, X.; Sun, J.
2018-02-01
Randomly distributed, static defects are enriched in ferroelastic domain walls. The relative concentration of defects in walls, Nd, follows a power law distribution as a function of the total defect concentration C: N d ˜ C α with α = 0.4 . The enrichment Nd/C ranges from ˜50 times when C = 10 ppm to ˜3 times when C = 1000 ppm. The resulting enrichment is due to nucleation at defect sites as observed in large scale MD simulations. The dynamics of domain nucleation and switching is dependent on the defect concentration. Their energy distribution follows the power law with exponents during yield between ɛ ˜ 1.82 and 2.0 when the defect concentration increases. The power law exponent is ɛ ≈ 2.7 in the plastic regime, independent of the defect concentration.
45 CFR 80.3 - Discrimination prohibited.
Code of Federal Regulations, 2011 CFR
2011-10-01
... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.3 Discrimination prohibited. (a) General. No person in the...
45 CFR 80.3 - Discrimination prohibited.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.3 Discrimination prohibited. (a) General. No person in the...
45 CFR 80.3 - Discrimination prohibited.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.3 Discrimination prohibited. (a) General. No person in the...
45 CFR 80.3 - Discrimination prohibited.
Code of Federal Regulations, 2012 CFR
2012-10-01
... Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.3 Discrimination prohibited. (a) General. No person in the...
Ahmedov, Merdin Lyutviev; Kemerdere, Rahsan; Baran, Oguz; Inal, Berrin Bercik; Gumus, Alper; Coskun, Cihan; Yeni, Seher Naz; Eren, Bulent; Uzan, Mustafa; Tanriverdi, Taner
2017-10-01
We sought to simply demonstrate how levels of soluble human epoxide hydrolase-2 show changes in both temporal the cortex and hippocampal complex in patients with temporal lobe epilepsy. A total of 20 patients underwent anterior temporal lobe resection due to temporal lobe epilepsy. The control group comprised 15 people who died in traffic accidents or by falling from a height, and their autopsy findings were included. Adequately sized temporal cortex and hippocampal samples were removed from each patient during surgery, and the same anatomic structures were removed from the control subjects during the autopsy procedures. Each sample was stored at -80°C as rapidly as possible until the enzyme assay. The temporal cortex in the epilepsy patients had a significantly higher enzyme level than did the temporal cortex of the control group (P = 0.03). Correlation analysis showed that as the enzyme level increases in the temporal cortex, it also increases in the hippocampal complex (r 2 = 0.06, P = 0.00001). More important, enzyme tissue levels showed positive correlations with seizure frequency in both the temporal cortex and hippocampal complex in patients (r 2 = 0.7, P = 0.00001 and r 2 = 0.4, P = 0.003, respectively). The duration of epilepsy was also positively correlated with the hippocampal enzyme level (r 2 = 0.06, P = 0.00001). Soluble human epoxy hydrolase enzyme-2 is increased in both lateral and medial temporal tissues in temporal lobe epilepsy. Further studies should be conducted as inhibition of this enzyme has resulted in a significant decrease in or stopping of seizures and attenuated neuroinflammation in experimental epilepsy models in the current literature. Copyright © 2017 Elsevier Inc. All rights reserved.
Structural Protein 4.1 in the Nucleus of Human Cells: Dynamic Rearrangements during Cell Division
Krauss, Sharon Wald; Larabell, Carolyn A.; Lockett, Stephen; Gascard, Philippe; Penman, Sheldon; Mohandas, Narla; Chasis, Joel Anne
1997-01-01
Structural protein 4.1, first identified as a crucial 80-kD protein in the mature red cell membrane skeleton, is now known to be a diverse family of protein isoforms generated by complex alternative mRNA splicing, variable usage of translation initiation sites, and posttranslational modification. Protein 4.1 epitopes are detected at multiple intracellular sites in nucleated mammalian cells. We report here investigations of protein 4.1 in the nucleus. Reconstructions of optical sections of human diploid fibroblast nuclei using antibodies specific for 80-kD red cell 4.1 and for 4.1 peptides showed 4.1 immunofluorescent signals were intranuclear and distributed throughout the volume of the nucleus. After sequential extractions of cells in situ, 4.1 epitopes were detected in nuclear matrix both by immunofluorescence light microscopy and resinless section immunoelectron microscopy. Western blot analysis of fibroblast nuclear matrix protein fractions, isolated under identical extraction conditions as those for microscopy, revealed several polypeptide bands reactive to multiple 4.1 antibodies against different domains. Epitope-tagged protein 4.1 was detected in fibroblast nuclei after transient transfections using a construct encoding red cell 80-kD 4.1 fused to an epitope tag. Endogenous protein 4.1 epitopes were detected throughout the cell cycle but underwent dynamic spatial rearrangements during cell division. Protein 4.1 was observed in nucleoplasm and centrosomes at interphase, in the mitotic spindle during mitosis, in perichromatin during telophase, as well as in the midbody during cytokinesis. These results suggest that multiple protein 4.1 isoforms may contribute significantly to nuclear architecture and ultimately to nuclear function. PMID:9128242
Andries, K; Dewindt, B; Snoeks, J; Willebrords, R; van Eemeren, K; Stokbroekx, R; Janssen, P A
1992-01-01
Pirodavir (R 77975) is the prototype of a novel class of broad-spectrum antipicornavirus compounds. Although its predecessor, R 61837, a substituted phenyl-pyridazinamine, was effective in inhibiting 80% of 100 serotypes tested (EC80) at concentrations above 32 micrograms/ml, pirodavir inhibits the same percentage of viruses at 0.064 micrograms/ml. Whereas R 61837 was active almost exclusively against rhinovirus serotypes of antiviral group B, pirodavir is broad spectrum in that it is highly active against both group A and group B rhinovirus serotypes. Pirodavir is also effective in inhibiting 16 enteroviruses, with an EC80 of 1.3 micrograms/ml. Susceptible rhinovirus serotypes were rendered noninfectious by direct contact with the antiviral compound. Their infectivity was not restored by dilution of virus-drug complexes, but was regained by organic solvent extraction of the compound for most serotypes. Neutralized viruses became stabilized to acid and heat, strongly suggesting a direct interaction of the compounds with viral capsid proteins. Mutants resistant to R 61837 (up to 85 times the MIC) were shown to bear some cross-resistance (up to 23 times the MIC) to the new compound, indicating that pirodavir also binds into the hydrophobic pocket beneath the canyon floor of rhinoviruses. Pirodavir acts at an early stage of the viral replication cycle (up to 40 min after infection) and reduces the yield of selected rhinoviruses 1,000- to 100,000-fold in a single round of replication. The mode of action appears to be serotype specific, since pirodavir was able to inhibit the adsorption of human rhinovirus 9 but not that of human rhinovirus 1A. Pirodavir is a novel capsid-binding antipicornavirus agent with potent in vitro activity against both group A and group B rhinovirus serotypes. PMID:1317142
45 CFR 80.11 - Judicial review.
Code of Federal Regulations, 2012 CFR
2012-10-01
... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.11 Judicial review. Action taken pursuant to section 602 of the Act...
45 CFR 80.11 - Judicial review.
Code of Federal Regulations, 2014 CFR
2014-10-01
... Welfare Department of Health and Human Services GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.11 Judicial review. Action taken pursuant to section 602 of the Act...
45 CFR 80.11 - Judicial review.
Code of Federal Regulations, 2010 CFR
2010-10-01
... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.11 Judicial review. Action taken pursuant to section 602 of the Act...
45 CFR 80.11 - Judicial review.
Code of Federal Regulations, 2013 CFR
2013-10-01
... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.11 Judicial review. Action taken pursuant to section 602 of the Act...
45 CFR 80.11 - Judicial review.
Code of Federal Regulations, 2011 CFR
2011-10-01
... Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING FEDERAL ASSISTANCE THROUGH THE DEPARTMENT OF HEALTH AND HUMAN SERVICES EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.11 Judicial review. Action taken pursuant to section 602 of the Act...
Code of Federal Regulations, 2010 CFR
2010-10-01
... 42 Public Health 2 2010-10-01 2010-10-01 false Basic rules. 408.80 Section 408.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM PREMIUMS FOR SUPPLEMENTARY MEDICAL INSURANCE Direct Remittance: Group Payment § 408.80 Basic rules. (a...
Vasireddi, Mugdha
2012-01-01
B virus of the family Herpesviridae is endemic to rhesus macaques but results in 80% fatality in untreated humans who are zoonotically infected. Downregulation of major histocompatibility complex (MHC) class I in order to evade CD8+ T-cell activation is characteristic of most herpesviruses. Here we examined the cell surface presence and total protein expression of MHC class I molecules in B virus-infected human foreskin fibroblast cells and macaque kidney epithelial cells in culture, which are representative of foreign and natural host initial target cells of B virus. Our results show <20% downregulation of surface MHC class I molecules in either type of host cells infected with B virus, which is statistically insignificantly different from that observed in uninfected cells. We also examined the surface expression of MHC class Ib molecules, HLA-E and HLA-G, involved in NK cell inhibition. Our results showed significant upregulation of HLA-E and HLA-G in host cells infected with B virus relative to the amounts observed in other herpesvirus-infected cells. These results suggest that B virus-infected cell surfaces maintain normal levels of MHC class Ia molecules, a finding unique among simplex viruses. This is a unique divergence in immune evasion for B virus, which, unlike human simplex viruses, does not inhibit the transport of peptides for loading onto MHC class Ia molecules because B virus ICP47 lacks a transporter-associated protein binding domain. The fact that MHC class Ib molecules were significantly upregulated has additional implications for host-pathogen interactions. PMID:22973043
Breast tumor targeting with (99m)Tc-HYNIC-PR81 complex as a new biologic radiopharmaceutical.
Salouti, Mojtaba; Rajabi, Hossein; Babaei, Mohammad Hossein; Rasaee, Mohammad Javad
2008-10-01
Human epithelial mucin, MUC1, is commonly overexpressed in adenocarcinoma that includes more than 80% of breast cancers. The PR81 is a murine anti-MUC1 monoclonal antibody (MAb) that was prepared against the human breast cancer. We developed an indirect method for labeling of this antibody with (99m)Tc in order to use the new preparation in immunoscintigraphy studies of BALB/c mice bearing breast tumors. The (99m)Tc-PR81 complex was prepared using the HYNIC as a chelator and tricine as a coligand. The labeling efficiency determined by instant thin-layer chromatography (ITLC) was 89.2%+/-4.7%, and radiocolloides measured by cellulose nitrate electrophoresis were 3.4%+/-0.9%. The in vitro stability of labeled product was determined at room temperature by ITLC and in human serum by gel filtration chromatography - 88.3%+/-4.6% and 79.8%+/-5.7% over 24 h, respectively. The integrity of labeled MAb was checked by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis, and no significant fragmentation was seen. The results of cell binding studies showed that both labeled and unlabeled PR81 were able to compete for binding to MCF 7 cells. Biodistribution studies performed in female BALB/c mice with breast tumor xenografts at 4, 16 and 24 h after the (99m)Tc-HYNIC-PR81 injection demonstrated a specific localization of the compound at the site of tumors and minimum accumulation in non target organs. The tumor imaging was performed in BALB/c mice with breast xenograft tumors at 4, 8, 12, 16, 20, 24, 28, 32 and 36 h after the complex injection. The tumors were visualized with high sensitivity after 8 h. The findings showed that the new radiopharmaceutical is a promising candidate for radioimmunoscintigraphy of the human breast cancer.
NASA Astrophysics Data System (ADS)
Amerikheirabadi, Fatemeh
Organic Donor-Acceptor complexes form the main component of the organic photovoltaic devices (OPVs). The open circuit voltage of OPVs is directly related to the charge transfer excited state energies of these complexes. Currently a large number of different molecular complexes are being tested for their efficiency in photovoltaic devices. In this work, density functional theory as implemented in the NRLMOL code is used to investigate the electronic structure and related properties of these donor-acceptor complexes. The charge transfer excitation energies are calculated using the perturbative delta self-consistent field method recently developed in our group as the standard time dependent density functional approaches fail to accurately provide them. The model photovoltaics systems analyzed are as follows: Sc3N C 80--ZnTPP, Y3 N C80-- ZnTPP and Sc3 N C80-- ZnPc. In addition, a thorough analysis of the isolated donor and acceptor molecules is also provided. The studied acceptors are chosen from a class of fullerenes named trimetallic nitride endohedral fullerenes. These molecules have shown to possess advantages as acceptors such as long lifetimes of the charge-separated states.
21 CFR 172.623 - Carrageenan with polysorbate 80.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Carrageenan with polysorbate 80. 172.623 Section 172.623 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Gums, Chewing Gum...
Kazemi, Zahra; Amiri Rudbari, Hadi; Mirkhani, Valiollah; Sahihi, Mehdi; Moghadam, Majid; Tangestaninejad, Shahram; Mohammadpoor-Baltork, Iraj; Kajani, Abolghasem Abbasi; Azimi, Gholamhassan
2017-07-28
The reaction of a racemic mixture of Schiff base tridentate ligand with vanadium(V) affords homochiral vanadium complex, (VO(R-L)) 2 O and (VO(S-L)) 2 O due to ligand "self-recognition" process. The formation of homochiral vanadium complex was confirmed by 1 H NMR, 13 C NMR and X-ray diffraction. The HSA- and DNA-binding of the resultant complex is assessed by absorption, fluorescence and circular dichroism (CD) spectroscopy methods. Based on the results, the HSA- and DNA-binding constant, K b , were found to be 8.0 × 10 4 and 1.9 × 10 5 M -1 , respectively. Interestingly, in vitro cytotoxicity assay revealed the potent anticancer activity of this complex on two prevalent cancer cell lines of MCF-7 (IC50 value of 14 μM) and HeLa (IC50 value of 36 μM), with considerably low toxicity on normal human fibroblast cells. The maximum cell mortality of 12.3% obtained after 48 h incubation of fibroblast cells with 100 μM of the complex. Additionally, the specific DNA- and HSA-binding was also shown using molecular docking method. The synthesized complex displayed high potential for biomedical applications especially for development of novel and efficient anticancer agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Parameterization models for pesticide exposure via crop consumption.
Fantke, Peter; Wieland, Peter; Juraske, Ronnie; Shaddick, Gavin; Itoiz, Eva Sevigné; Friedrich, Rainer; Jolliet, Olivier
2012-12-04
An approach for estimating human exposure to pesticides via consumption of six important food crops is presented that can be used to extend multimedia models applied in health risk and life cycle impact assessment. We first assessed the variation of model output (pesticide residues per kg applied) as a function of model input variables (substance, crop, and environmental properties) including their possible correlations using matrix algebra. We identified five key parameters responsible for between 80% and 93% of the variation in pesticide residues, namely time between substance application and crop harvest, degradation half-lives in crops and on crop surfaces, overall residence times in soil, and substance molecular weight. Partition coefficients also play an important role for fruit trees and tomato (Kow), potato (Koc), and lettuce (Kaw, Kow). Focusing on these parameters, we develop crop-specific models by parametrizing a complex fate and exposure assessment framework. The parametric models thereby reflect the framework's physical and chemical mechanisms and predict pesticide residues in harvest using linear combinations of crop, crop surface, and soil compartments. Parametric model results correspond well with results from the complex framework for 1540 substance-crop combinations with total deviations between a factor 4 (potato) and a factor 66 (lettuce). Predicted residues also correspond well with experimental data previously used to evaluate the complex framework. Pesticide mass in harvest can finally be combined with reduction factors accounting for food processing to estimate human exposure from crop consumption. All parametric models can be easily implemented into existing assessment frameworks.
Fisher, R P; Topper, J N; Clayton, D A
1987-07-17
Selective transcription of human mitochondrial DNA requires a transcription factor (mtTF) in addition to an essentially nonselective RNA polymerase. Partially purified mtTF is able to sequester promoter-containing DNA in preinitiation complexes in the absence of mitochondrial RNA polymerase, suggesting a DNA-binding mechanism for factor activity. Functional domains, required for positive transcriptional regulation by mtTF, are identified within both major promoters of human mtDNA through transcription of mutant promoter templates in a reconstituted in vitro system. These domains are essentially coextensive with DNA sequences protected from nuclease digestion by mtTF-binding. Comparison of the sequences of the two mtTF-responsive elements reveals significant homology only when one sequence is inverted; the binding sites are in opposite orientations with respect to the predominant direction of transcription. Thus mtTF may function bidirectionally, requiring additional protein-DNA interactions to dictate transcriptional polarity. The mtTF-responsive elements are arrayed as direct repeats, separated by approximately 80 bp within the displacement-loop region of human mitochondrial DNA; this arrangement may reflect duplication of an ancestral bidirectional promoter, giving rise to separate, unidirectional promoters for each strand.
Hypersensitivity reaction to human papillomavirus vaccine due to polysorbate 80.
Badiu, Iuliana; Geuna, Massimo; Heffler, Enrico; Rolla, Giovanni
2012-05-08
A 17-year-old girl reported generalised urticaria, eyelid angioedema, rhino-conjunctivitis, dyspnoea and wheezing 1 h after third intramuscular administration of quadrivalent human papilloma virus vaccine (Gardasil). She was treated with antihistamine, and corticosteroids with prompt relief of rhinitis and dyspnoea, while urticaria and angioedema lasted 24 h. Intradermal test with Gardasil, which contains polysorbate 80 (PS80), resulted positive, while skin tests with the bivalent vaccine were negative. Prick test performed with PS80 resulted positive in the patient and negative in ten healthy controls. The CD203 basophil activation test result was negative for PS80 at all the tested dilutions and specific IgE was not found. As flu vaccine was recommended, the authors skin tested two flu vaccine, one containing PS80 (Fluarix, GSK), which resulted positive and another flu vaccine with no adjuvant or preservative (Vaxigrip, Sanofi Pasteur MSD), which gave negative results. The patient then received Vaxigrip without adverse reactions.
Hofling-Lima, Ana Luisa; Pignatari, Antonio C. C.
2014-01-01
Staphylococcus epidermidis is an abundant member of the microbiota of the human skin and wet mucosa, which is commonly associated with sight-threatening infections in eyes with predisposing factors. Ocular S. epidermidis has become notorious because of its capability to form biofilms on different ocular devices and due to the evolving rates of antimicrobial resistance. In this study, the molecular epidemiology of 30 ocular methicillin-resistant S. epidermidis (MRSE) isolates was assessed using multilocus sequence typing (MLST). Antimicrobial resistance, accessory gene-regulator and staphylococcal cassette chromosome mec (SCCmec) types, biofilm formation, and the occurrence of biofilm-associated genes were correlated with MLST clonal complexes. Sequence types (STs) frequently found in the hospital setting were rarely found in our collection. Overall, 12 different STs were detected with a predominance of ST59 (30%), ST5 and ST6 (13.3% each). Most of the isolates (93.3%) belonged to the clonal complex 2 (CC2) and grouped mainly within subcluster CC2-II (92.9%). Isolates grouped within this subcluster were frequently biofilm producers (92.3%) with a higher occurrence of the aap (84.5%) and bhp (46.1%) genes compared to icaA (19.2%). SCCmec type IV (53.8%) was predominant within CC2-II strains, while 38.4% were nontypeable. In addition, CC2-II strains were frequently multidrug resistant (80.7%) and demonstrated to be particularly resistant to ciprofloxacin (80.8%), ofloxacin (77%), azithromycin (61.5%), and gentamicin (57.7%). Our findings demonstrate the predominance of a particular MRSE cluster causing ocular infections, which was associated with high rates of antimicrobial resistance and particularly the carriage of biofilm-related genes coding for proteinaceous factors implicated in biofilm accumulation. PMID:24523473
Microtubule Depolymerization as a Driver for Chromosome Motion
NASA Astrophysics Data System (ADS)
McIntosh, Richard
2014-03-01
Microtubules (MTs) are rigid polymers of the protein, tubulin, which function as intracellular struts. They are also tracks along which motor enzymes can run, carrying cargo to specific cellular locations. Most MTs are dynamic; they assemble and disassemble rapidly, particularly during cell division when the cell forms the ``mitotic spindle,'' a machine that organizes the duplicated chromosomes into a planar disk, then pulls the duplicate copies apart, moving them to opposite ends of the cell. This process is necessary for the daughter cells to have a full complement of DNA. The mitotic spindle is a labile framework that exerts several kinds of forces on the chromosomes to move them in well organized ways. It contains many motor enzymes that contribute to spindle formation, but genetic evidence shows that the motors that attach to chromosomes and might contribute to chromosome motion are dispensable for normal mitosis. Apparently MT dynamics can also serve as a motor and is an important source of force for chromosome motion. We have studied this process and find that MTs can be coupled to a load by specific spindle proteins so that MT depolymerization can exert substantial force. With the yeast protein, Dam1, a single MT can generate 30 pN, about 5-fold more than is generated by a motor enzyme like kinesin or myosin. The resulting motions are processive, so a depolymerizing MT can carry its load for many micrometers. However, Dam1 is found only in fungi. We have therefore sought other proteins that can serve as analogous couplers. Several MT-dependent motor enzymes can do the job in ways that do not require ATP, their normal source of energy. Some non-motor MT-associated proteins will also work, e.g., the kinetochore proteins NDC80 and CENP-F. Data will be presented that show the strengths and weaknesses of each coupler, allowing some generalization about how the mitotic machinery works. Supported by NIH GM033787.
19. Power plant engine pipinglower level plan, sheet 80 of ...
19. Power plant engine piping-lower level plan, sheet 80 of 130 - Naval Air Station Fallon, Power Plant, 800 Complex, off Carson Road near intersection of Pasture & Berney Roads, Fallon, Churchill County, NV
Competing endogenous RNA and interactome bioinformatic analyses on human telomerase.
Arancio, Walter; Pizzolanti, Giuseppe; Genovese, Swonild Ilenia; Baiamonte, Concetta; Giordano, Carla
2014-04-01
We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT. The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex. Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres. Telomere dysfunctions have been widely reported to be involved in aging, cancer, and cellular senescence. The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid.org/) and related analysis tools such as Osprey (http://biodata.mshri.on.ca/osprey/servlet/Index) and GeneMANIA (http://genemania.org/). The network of interaction of hTERT transcripts has been further analyzed following the competing endogenous (ce) RNA hypotheses (messenger [m] RNAs cross-talk via micro [mi] RNAs) using the miRWalk database and tools (www.ma.uni-heidelberg.de/apps/zmf/mirwalk/). These analyses suggest a role for Akt, nuclear factor-κB (NF-κB), heat shock protein 90 (HSP90), p70/p80 autoantigen, 14-3-3 proteins, and dynein in telomere functions. Roles for histone acetylation/deacetylation and proteoglycan metabolism are also proposed.
Testosterone, oxytocin, and the development of human parental care.
Gordon, Ilanit; Pratt, Maayan; Bergunde, Katharina; Zagoory-Sharon, Orna; Feldman, Ruth
2017-07-01
The steroid testosterone (T) and neuropeptide oxytocin (OT) have each been implicated in the development of parental care in humans and animals, yet very little research addressed the interaction between these hormones at the transition to parenthood in mothers and fathers. One hundred and sixty mothers and fathers (80 couples) were visited 1 and 6months after the birth of their first child, plasma OT and T were assayed at each time-point, and interactions between each parent and the infant were observed and micro-coded for two key parental behaviors; affectionate touch and parent-infant synchrony. T showed gender-specific effects. While paternal T was individually stable across the first six months of parenting and predicted lower father-infant synchrony, maternal T was neither stable nor predictive of maternal behavior. An interaction of OT and T showed that T has complex modulatory effects on the relations of OT and parenting. Slope analysis revealed that among fathers, only when T was high (+1SD), negative associations emerged between OT and father affectionate touch. In contrast, among mothers, the context of high T was related to a positive association between OT and maternal touch. Our findings, the first to test the interaction of OT and T in relation to observed maternal behavior, underscore the need for much further research on the complex bidirectional effects of steroid and neuropeptide systems on human mothering and fathering. Copyright © 2017 Elsevier Inc. All rights reserved.
Measurement of angular velocity in the perception of rotation.
Barraza, José F; Grzywacz, Norberto M
2002-09-01
Humans are sensitive to the parameters of translational motion, namely, direction and speed. At the same time, people have special mechanisms to deal with more complex motions, such as rotations and expansions. One wonders whether people may also be sensitive to the parameters of these complex motions. Here, we report on a series of experiments that explore whether human subjects can use angular velocity to evaluate how fast a rotational motion is. In four experiments, subjects were required to perform a task of speed-of-rotation discrimination by comparing two annuli of different radii in a temporal 2AFC paradigm. Results showed that humans could rely on a sensitive measurement of angular velocity to perform this discrimination task. This was especially true when the quality of the rotational signal was high (given by the number of dots composing the annulus). When the signal quality decreased, a bias towards linear velocity of 5-80% appeared, suggesting the existence of separate mechanisms for angular and linear velocity. This bias was independent from the reference radius. Finally, we asked whether the measurement of angular velocity required a rigid rotation, that is, whether the visual system makes only one global estimate of angular velocity. For this purpose, a random-dot disk was built such that all the dots were rotating with the same tangential speed, irrespectively of radius. Results showed that subjects do not estimate a unique global angular velocity, but that they perceive a non-rigid disk, with angular velocity falling inversely proportionally with radius.
Irradiation-induced damage evolution in concentrated Ni-based alloys
Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou; ...
2017-06-06
Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less
Irradiation-induced damage evolution in concentrated Ni-based alloys
DOE Office of Scientific and Technical Information (OSTI.GOV)
Velisa, Gihan; Ullah, Mohammad Wali; Xue, Haizhou
Understanding the effects of chemical complexity from the number, type and concentration of alloying elements in single-phase concentred solid-solution alloys (SP-CSAs) on defect dynamics and microstructure evolution is pivotal for developing next-generation radiation-tolerant structural alloys. A specially chosen set of SP-CSAs with different chemical complexity (Ni 80Fe 20, Ni 80Cr 20 and Ni 40Fe 40Cr 20) are investigated using 1.5 MeV Mn ions over a wide fluence range, from 2 × 10 13 to 1 × 10 16 ions cm –2 at room temperature. Based on an integrated study of Rutherford backscattering spectroscopy in channeling geometry and molecular dynamics simulations,more » the results demonstrate that Ni 40Fe 40Cr 20 is more radiation tolerant than Ni 80Fe 20, Ni 80Cr 20 and elemental Ni in the low fluence regime. While chemical complexity of this set of SP-CSAs is clearly demonstrated to affect defect evolution through suppressed defect production and enhanced recombination at early stages, the effect of the mixed ferro- and anti-ferromagnetic interactions is not the only controlling factor responsible for the improved radiation performance. As a result, the observed strong alloying effect on defect evolution is attributed to the altered defect migration mobilities of defect clusters in these alloys, an intrinsic characteristic of the complex energy landscapes in CSAs.« less
NASA Technical Reports Server (NTRS)
George, Kerry; Hada, Megumi; Cucinotta, F. A.
2011-01-01
Chromosomal aberrations were measured in human peripheral blood lymphocytes after in vitro exposure to neon ions at energies of 64, 89, 142, or 267. The corresponding LET values for these energies of neon ranged from 38-103 keV/micrometers and doses delivered were in the 10 to 80 cGy range. Chromosome exchanges were assessed in metaphase and G2 phase cells at first division after exposure using fluorescence in situ hybridization (FISH) with whole chromosome probes and dose response curves were generated for different types of chromosomal exchanges. The yields of total chromosome exchanges were similar for the 64, 89, and 142 MeV exposures, whereas the 267 MeV/u neon with LET of 38 keV/micrometers produced about half as many exchanges per unit dose. The induction of complex type chromosome exchanges (exchanges involving three or more breaks and two or more chromosomes) showed a clear LET dependence for all energies. The ratio of simple to complex type exchanges increased with LET from 18 to 51%. The relative biological effectiveness (RBE) was estimated from the initial slope of the dose response curve for chromosome damage with respect to gamma-rays. The RBE(sub max) values for total chromosome exchanges for the 64 MeV/u was around 30.
Cichy, Radoslaw Martin; Pantazis, Dimitrios; Oliva, Aude
2016-01-01
Every human cognitive function, such as visual object recognition, is realized in a complex spatio-temporal activity pattern in the brain. Current brain imaging techniques in isolation cannot resolve the brain's spatio-temporal dynamics, because they provide either high spatial or temporal resolution but not both. To overcome this limitation, we developed an integration approach that uses representational similarities to combine measurements of magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) to yield a spatially and temporally integrated characterization of neuronal activation. Applying this approach to 2 independent MEG–fMRI data sets, we observed that neural activity first emerged in the occipital pole at 50–80 ms, before spreading rapidly and progressively in the anterior direction along the ventral and dorsal visual streams. Further region-of-interest analyses established that dorsal and ventral regions showed MEG–fMRI correspondence in representations later than early visual cortex. Together, these results provide a novel and comprehensive, spatio-temporally resolved view of the rapid neural dynamics during the first few hundred milliseconds of object vision. They further demonstrate the feasibility of spatially unbiased representational similarity-based fusion of MEG and fMRI, promising new insights into how the brain computes complex cognitive functions. PMID:27235099
Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle
NASA Astrophysics Data System (ADS)
Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu; Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin
2013-10-01
A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly( d, l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.
Konarev, Dmitri V.; Zorina, Leokadiya V.; Khasanov, Salavat S.; Popov, Alexey A.; Otsuka, Akihiro; Yamochi, Hideki; Saito, Gunzi; Lyubovskaya, Rimma N.
2017-01-01
Reduction of scandium nitride clusterfullerene, Sc3N@Ih-C80, by sodium fluorenone ketyl in the presence of cryptand[2,2,2] allows the crystallization of the {cryptand[2,2,2](Na+)}2(Sc3N@Ih-C80−)2·2.5C6H4Cl2 (1) salt. The Sc3N@Ih-C80•− radical anions are dimerized to form single-bonded (Sc3N@Ih-C80−)2 dimers. PMID:27511304
Kankowski, Svenja; Förstera, Benjamin; Winkelmann, Aline; Knauff, Pina; Wanker, Erich E.; You, Xintian A.; Semtner, Marcus; Hetsch, Florian; Meier, Jochen C.
2018-01-01
C-to-U RNA editing of glycine receptors (GlyR) can play an important role in disease progression of temporal lobe epilepsy (TLE) as it may contribute in a neuron type-specific way to neuropsychiatric symptoms of the disease. It is therefore necessary to develop tools that allow identification of neuron types that express RNA-edited GlyR protein. In this study, we identify NH4 as agonist of C-to-U RNA edited GlyRs. Furthermore, we generated a new molecular C-to-U RNA editing sensor tool that detects Apobec-1- dependent RNA editing in HEPG2 cells and rat primary hippocampal neurons. Using this sensor combined with NH4 application, we were able to identify C-to-U RNA editing-competent neurons and expression of C-to-U RNA-edited GlyR protein in neurons. Bioinformatic analysis of 1,000 Genome Project Phase 3 allele frequencies coding for human Apobec-1 80M and 80I variants showed differences between populations, and the results revealed a preference of the 80I variant to generate RNA-edited GlyR protein. Finally, we established a new PCR-based restriction fragment length polymorphism (RFLP) approach to profile mRNA expression with regard to the genetic APOBEC1 dimorphism of patients with intractable temporal lobe epilepsy (iTLE) and found that the patients fall into two groups. Patients with expression of the Apobec-1 80I variant mostly suffered from simple or complex partial seizures, whereas patients with 80M expression exhibited secondarily generalized seizure activity. Thus, our method allows the characterization of Apobec-1 80M and 80l variants in the brain and provides a new way to epidemiologically and semiologically classify iTLE according to the two different APOBEC1 alleles. Together, these results demonstrate Apobec-1-dependent expression of RNA-edited GlyR protein in neurons and identify the APOBEC1 80I/M-coding alleles as new genetic risk factors for iTLE patients. PMID:29375302
Ocean commitments under the Paris Agreement
NASA Astrophysics Data System (ADS)
Gallo, Natalya D.; Victor, David G.; Levin, Lisa A.
2017-11-01
Under the Paris Agreement nations made pledges known as nationally determined contributions (NDCs), which indicate how national governments are evaluating climate risks and policy opportunities. We find that NDCs reveal important systematic patterns reflecting national interests and capabilities. Because the ocean plays critical roles in climate mitigation and adaptation, we created a quantitative marine focus factor (MFF) to evaluate how governments address marine issues. In contrast to the past, when oceans received minimal attention in climate negotiations, 70% of 161 NDCs we analysed include marine issues. The percentage of the population living in low-lying areas--vulnerable to rising seas--positively influences the MFF, but negotiating group (Annex 1 or small island developing states) is equally important, suggesting political motivations are crucial to NDC development. The analysis reveals gaps between scientific and government attention, including on ocean deoxygenation, which is barely mentioned. Governments display a keen interest in expanding marine research on climate priorities.
Gene silencing activity of siRNA polyplexes based on thiolated N,N,N-trimethylated chitosan.
Varkouhi, Amir K; Verheul, Rolf J; Schiffelers, Raymond M; Lammers, Twan; Storm, Gert; Hennink, Wim E
2010-12-15
N,N,N-Trimethylated chitosan (TMC) is a biodegradable polymer emerging as a promising nonviral vector for nucleic acid and protein delivery. In the present study, we investigated whether the introduction of thiol groups in TMC enhances the extracellular stability of the complexes based on this polymer and promotes the intracellular release of siRNA. The gene silencing activity and the cellular cytotoxicity of polyplexes based on thiolated TMC were compared with those based on the nonthiolated counterpart and the regularly used lipidic transfection agent Lipofectamine. Incubation of H1299 human lung cancer cells expressing firefly luciferase with siRNA/thiolated TMC polyplexes resulted in 60-80% gene silencing activity, whereas complexes based on nonthiolated TMC showed less silencing (40%). The silencing activity of the complexes based on Lipofectamine 2000 was about 60-70%. Importantly, the TMC-SH polyplexes retained their silencing activity in the presence of hyaluronic acid, while nonthiolated TMC polyplexes hardly showed any silencing activity, demonstrating their stability against competing anionic macromolecules. Under the experimental conditions tested, the cytotoxicity of the thiolated and nonthiolated siRNA complexes was lower than those based on Lipofectamine. Given the good extracellular stability and good silencing activity, it is concluded that polyplexes based on TMC-SH are attractive systems for further in vivo evaluations.
Zhao, Ling-Jun; Loewenstein, Paul M; Green, Maurice
2016-12-01
The adenovirus E1A 243R oncoprotein targets TRRAP, a scaffold protein that assembles histone acetyltransferase (HAT) complexes, such as the NuA4/Tip60 complex which mediates transcriptional activity of the proto-oncogene MYC and helps determine the cancer cell phenotype. How E1A transforms cells through TRRAP remains obscure. We performed proteomic analysis with the N-terminal transcriptional repression domain of E1A 243R (E1A 1-80) and showed that E1A 1-80 interacts with TRRAP, p400, and three other members of the NuA4 complex - DMAP1, RUVBL1 and RUVBL2 - not previously shown to associate with E1A 243R. E1A 1-80 interacts with these NuA4 components and MYC through the E1A TRRAP-targeting domain. E1A 243R association with the NuA4 complex was demonstrated by co-immunoprecipitation and analysis with DMAP1, Tip60, and MYC. Significantly, E1A 243R promotes association of MYC/MAX with the NuA4/Tip60 complex, implicating the importance of the MYC/NuA4 pathway in cellular transformation by both MYC and E1A. Copyright © 2016 Elsevier Inc. All rights reserved.
A negative regulatory role in mouse cardiac transplantation for a splice variant of CD80.
Bugeon, Laurence; Wong, Kenneth K; Rankin, Alasdair M; Hargreaves, Roseanna E G; Dallman, Margaret J
2006-11-27
Members of the B7 costimulatory protein family (CD80 and CD86) play a determining role in allograft rejection. Both CD80 and CD86 have naturally occurring splice variants whose roles in transplantation are unknown. Full length CD80 has two immunoglobulin (Ig)-like domains in the extracellular portion, IgC and IgV. In mouse, the isoform IgV-CD80 lacks the IgC-like domain. Here we analyzed the role of mouse IgV-CD80 in heart allograft rejection and search for equivalent splice variants in human. Mice made deficient for full-length CD80 but which retain expression of the shorter IgV-CD80 (CD80 mice) were used as donor or recipient of a heart allograft. Recipient animals were untreated or pretreated with alloantigen expressing cells and/or treated with CD80 and CTLA4 monoclonal antibodies (mAbs). Recipients expressing IgV-CD80 but not full length CD80 exhibited a slight prolongation in survival of either wild-type (Wt) or CD80 grafts. More dramatically, CD80 animals pretreated with donor alloantigen exhibited permanent graft survival, whereas their Wt counterparts rejected their grafts with a median survival of 24 days. This prolonged survival was due to the expression of IgV-CD80 in recipients since treatment with CD80 mAb abrogated the beneficial effect observed. We identified and report here a similar isoform of CD80 from human cDNA encoding a putative soluble, IgV-containing protein. IgV-CD80 bearing recipients show enhanced allograft survival especially after donor alloantigen pretreatment. This together with data from other species suggests that regulation delivered by splice variants of CD80 significantly modulates immunity and may be common across the species.
40 CFR 165.80 - General provisions.
Code of Federal Regulations, 2014 CFR
2014-07-01
... subpart is to protect human health and the environment from exposure to agricultural pesticides which may....80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Standards for Pesticide Containment Structures § 165.80 General provisions. (a) What...
40 CFR 165.80 - General provisions.
Code of Federal Regulations, 2012 CFR
2012-07-01
... subpart is to protect human health and the environment from exposure to agricultural pesticides which may....80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Standards for Pesticide Containment Structures § 165.80 General provisions. (a) What...
40 CFR 165.80 - General provisions.
Code of Federal Regulations, 2011 CFR
2011-07-01
... subpart is to protect human health and the environment from exposure to agricultural pesticides which may....80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Standards for Pesticide Containment Structures § 165.80 General provisions. (a) What...
40 CFR 165.80 - General provisions.
Code of Federal Regulations, 2013 CFR
2013-07-01
... subpart is to protect human health and the environment from exposure to agricultural pesticides which may....80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Standards for Pesticide Containment Structures § 165.80 General provisions. (a) What...
40 CFR 165.80 - General provisions.
Code of Federal Regulations, 2010 CFR
2010-07-01
... subpart is to protect human health and the environment from exposure to agricultural pesticides which may....80 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS PESTICIDE MANAGEMENT AND DISPOSAL Standards for Pesticide Containment Structures § 165.80 General provisions. (a) What...
42 CFR 476.80 - Coordination with Medicare fiscal intermediaries and carriers.
Code of Federal Regulations, 2010 CFR
2010-10-01
... and carriers. 476.80 Section 476.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) QUALITY IMPROVEMENT ORGANIZATIONS UTILIZATION AND QUALITY CONTROL REVIEW Review Responsibilities of Utilization and Quality Control Quality Improvement...
NASA Technical Reports Server (NTRS)
Boulanger, Richard; Overland, David
2004-01-01
Technologies that facilitate the design and control of complex, hybrid, and resource-constrained systems are examined. This paper focuses on design methodologies, and system architectures, not on specific control methods that may be applied to life support subsystems. Honeywell and Boeing have estimated that 60-80Y0 of the effort in developing complex control systems is software development, and only 20-40% is control system development. It has also been shown that large software projects have failure rates of as high as 50-65%. Concepts discussed include the Unified Modeling Language (UML) and design patterns with the goal of creating a self-improving, self-documenting system design process. Successful architectures for control must not only facilitate hardware to software integration, but must also reconcile continuously changing software with much less frequently changing hardware. These architectures rely on software modules or components to facilitate change. Architecting such systems for change leverages the interfaces between these modules or components.
Masaki, S; Sugimori, G; Okamoto, A; Imose, J; Hayashi, Y
1991-01-01
The effects of Tween 80 supplementation of liquid culture medium on the formation of the superficial L1 layer of the Mycobacterium avium-Mycobacterium intracellulare complex (MAC) were examined by serological and scanning electron microscopic experiments. Specific antiserum to the glycopeptidolipids on the L1 layer of M. avium S-139, made in a rabbit, was used for seroagglutination reactions with antigens prepared from strain S-139 grown in medium supplemented with various levels of Tween 80 (0, 0.05, 0.5, 5, and 50 mg/ml). The agglutination titers gradually decreased as the concentration of Tween 80 rose. Scanning electron microscopy showed that the fibrillar materials consisting mainly of glycopeptidolipids on the L1 layer of strain S-139 also disappeared with increases in the concentration of Tween 80. In addition, there was no obvious correlation between (i) the plasmid DNAs and serotypes of MAC and (ii) formation of the L1 layer of MAC. It is therefore concluded that Tween 80 used to supplement liquid culture medium affects formation of the L1 layer, which has been considered to be one of the pathogenic factors of MAC. Images PMID:1885740
45 CFR 80.8 - Procedure for effecting compliance.
Code of Federal Regulations, 2011 CFR
2011-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.8 Procedure for effecting compliance. (a) General... appropriate. (Secs. 601, 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d, 2000d-1; sec. 182, 80... 80.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION...
45 CFR 80.8 - Procedure for effecting compliance.
Code of Federal Regulations, 2013 CFR
2013-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.8 Procedure for effecting compliance. (a) General... appropriate. (Secs. 601, 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d, 2000d-1; sec. 182, 80... 80.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION...
45 CFR 80.8 - Procedure for effecting compliance.
Code of Federal Regulations, 2010 CFR
2010-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.8 Procedure for effecting compliance. (a) General... appropriate. (Secs. 601, 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d, 2000d-1; sec. 182, 80... 80.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION...
45 CFR 80.8 - Procedure for effecting compliance.
Code of Federal Regulations, 2012 CFR
2012-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.8 Procedure for effecting compliance. (a) General... appropriate. (Secs. 601, 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d, 2000d-1; sec. 182, 80... 80.8 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION...
45 CFR 80.8 - Procedure for effecting compliance.
Code of Federal Regulations, 2014 CFR
2014-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.8 Procedure for effecting compliance. (a) General... appropriate. (Secs. 601, 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d, 2000d-1; sec. 182, 80... 80.8 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION NONDISCRIMINATION...
Substance Abuse by Elders and Self-Enhancement Bias
ERIC Educational Resources Information Center
Kane, Michael N.; Green, Diane
2009-01-01
Human service professionals regularly do not recognize the symptoms of substance abuse in older populations and are unlikely to provide intervention. In this study, human service students (N = 242) were given one of three vignettes in which the main character was an 80-year-old man, an 80-year-old woman, or they were asked to imagine themselves at…
21 CFR 1250.80 - Applicability.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Applicability. 1250.80 Section 1250.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION INTERSTATE CONVEYANCE...
21 CFR 1250.80 - Applicability.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Applicability. 1250.80 Section 1250.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION INTERSTATE CONVEYANCE...
Nucleolar proteins Bfr2 and Enp2 interact with DEAD-box RNA helicase Dbp4 in two different complexes
Soltanieh, Sahar; Lapensée, Martin; Dragon, François
2014-01-01
Different pre-ribosomal complexes are formed during ribosome biogenesis, and the composition of these complexes is highly dynamic. Dbp4, a conserved DEAD-box RNA helicase implicated in ribosome biogenesis, interacts with nucleolar proteins Bfr2 and Enp2. We show that, like Dbp4, Bfr2 and Enp2 are required for the early processing steps leading to the production of 18S ribosomal RNA. We also found that Bfr2 and Enp2 associate with the U3 small nucleolar RNA (snoRNA), the U3-specific protein Mpp10 and various pre-18S ribosomal RNA species. Thus, we propose that Bfr2, Dbp4 and Enp2 are components of the small subunit (SSU) processome, a large complex of ∼80S. Sucrose gradient sedimentation analyses indicated that Dbp4, Bfr2 and Enp2 sediment in a peak of ∼50S and in a peak of ∼80S. Bfr2, Dbp4 and Enp2 associate together in the 50S complex, which does not include the U3 snoRNA; however, they associate with U3 snoRNA in the 80S complex (SSU processome). Immunoprecipitation experiments revealed that U14 snoRNA associates with Dbp4 in the 50S complex, but not with Bfr2 or Enp2. The assembly factor Tsr1 is not part of the ‘50S’ complex, indicating this complex is not a pre-40S ribosome. A combination of experiments leads us to propose that Bfr2, Enp2 and Dbp4 are recruited at late steps during assembly of the SSU processome. PMID:24357410
Youmans, Daniel T; Schmidt, Jens C; Cech, Thomas R
2018-06-01
Polycomb-repressive complex 2 (PRC2) is a histone methyltransferase that promotes epigenetic gene silencing, but the dynamics of its interactions with chromatin are largely unknown. Here we quantitatively measured the binding of PRC2 to chromatin in human cancer cells. Genome editing of a HaloTag into the endogenous EZH2 and SUZ12 loci and single-particle tracking revealed that ∼80% of PRC2 rapidly diffuses through the nucleus, while ∼20% is chromatin-bound. Short-term treatment with a small molecule inhibitor of the EED-H3K27me3 interaction had no immediate effect on the chromatin residence time of PRC2. In contrast, separation-of-function mutants of SUZ12, which still form the core PRC2 complex but cannot bind accessory proteins, revealed a major contribution of AEBP2 and PCL homolog proteins to chromatin binding. We therefore quantified the dynamics of this chromatin-modifying complex in living cells and separated the contributions of H3K27me3 histone marks and various PRC2 subunits to recruitment of PRC2 to chromatin. © 2018 Youmans et al.; Published by Cold Spring Harbor Laboratory Press.
Pathogenicity of a Human Laminin β2 Mutation Revealed in Models of Alport Syndrome.
Funk, Steven D; Bayer, Raymond H; Malone, Andrew F; McKee, Karen K; Yurchenco, Peter D; Miner, Jeffrey H
2018-03-01
Pierson syndrome is a congenital nephrotic syndrome with eye and neurologic defects caused by mutations in laminin β 2 ( LAMB2 ), a major component of the glomerular basement membrane (GBM). Pathogenic missense mutations in human LAMB2 cluster in or near the laminin amino-terminal (LN) domain, a domain required for extracellular polymerization of laminin trimers and basement membrane scaffolding. Here, we investigated an LN domain missense mutation, LAMB2-S80R, which was discovered in a patient with Pierson syndrome and unusually late onset of proteinuria. Biochemical data indicated that this mutation impairs laminin polymerization, which we hypothesized to be the cause of the patient's nephrotic syndrome. Testing this hypothesis in genetically altered mice showed that the corresponding amino acid change (LAMB2-S83R) alone is not pathogenic. However, expression of LAMB2-S83R significantly increased the rate of progression to kidney failure in a Col4a3 -/- mouse model of autosomal recessive Alport syndrome and increased proteinuria in Col4a5 +/- females that exhibit a mild form of X-linked Alport syndrome due to mosaic deposition of collagen α 3 α 4 α 5(IV) in the GBM. Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This finding could help explain the wide range of Alport syndrome onset and severity observed in patients with Alport syndrome, even for family members who share the same COL4 mutation. Our results also show the complexities of using model organisms to investigate genetic variants suspected of being pathogenic in humans. Copyright © 2018 by the American Society of Nephrology.
21 CFR 211.80 - General requirements.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 4 2013-04-01 2013-04-01 false General requirements. 211.80 Section 211.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of Components and Drug...
21 CFR 211.80 - General requirements.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 4 2011-04-01 2011-04-01 false General requirements. 211.80 Section 211.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of Components and Drug...
21 CFR 211.80 - General requirements.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 4 2012-04-01 2012-04-01 false General requirements. 211.80 Section 211.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of Components and Drug...
21 CFR 211.80 - General requirements.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 4 2014-04-01 2014-04-01 false General requirements. 211.80 Section 211.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of Components and Drug...
21 CFR 1250.80 - Applicability.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Applicability. 1250.80 Section 1250.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... and the sanitary conditions on vessels engaged in interstate traffic shall comply with the...
21 CFR 1250.80 - Applicability.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Applicability. 1250.80 Section 1250.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... and the sanitary conditions on vessels engaged in interstate traffic shall comply with the...
21 CFR 1250.80 - Applicability.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Applicability. 1250.80 Section 1250.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS... and the sanitary conditions on vessels engaged in interstate traffic shall comply with the...
21 CFR 211.80 - General requirements.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 4 2010-04-01 2010-04-01 false General requirements. 211.80 Section 211.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of Components and Drug...
Shiohira, Hideo; Kitaoka, Akira; Enjoji, Munechika; Uno, Tsukasa; Nakashima, Manabu
2012-01-01
Am80, a synthetic retinoid, has been used in differentiation therapy for acute promyelocytic leukemia (APL). All-trans retinoic acid (ATRA) as one of natural retinoid has been also used to treat APL. ATRA treatment causes neuronal differentiation by inducing tropomyosin-related kinase B (TrkB) expression and increasing the sensitivity to brain-derived neurotrophic factor (BDNF), a TrkB ligand. In the present study, we investigated the effects of Am80 on neuronal differentiation, BDNF sensitivity and TrkB expression in human neuroblastoma SH-SY5Y cells. Treatment with Am80 induced morphological differentiation of neurite outgrowth and increased the expression of GAP43 mRNA, a neuronal differentiation marker. Additionally, TrkB protein was also increased, and exogenous BDNF stimulation after treatment with Am80 induced greater neurite outgrowth than without BDNF treatment. These results suggest that Am80 induced neuronal differentiation by increasing TrkB expression and BDNF sensitivity.
Seismological investigation of the National Data Centre Preparedness Exercise 2013
NASA Astrophysics Data System (ADS)
Gestermann, Nicolai; Hartmann, Gernot; Ross, J. Ole; Ceranna, Lars
2015-04-01
The Comprehensive Nuclear-Test-Ban Treaty (CTBT) prohibits all kinds of nuclear explosions conducted on Earth - underground, underwater or in the atmosphere. The verification regime of the CTBT is designed to detect any treaty violation. While the data of the International Monitoring System (IMS) is collected, processed and technically analyzed at the International Data Centre (IDC) of the CTBT-Organization, National Data Centres (NDC) of the member states provide interpretation and advice to their government concerning suspicious detections. The NDC Preparedness Exercises (NPE) are regularly performed dealing with fictitious treaty violations to practice the combined analysis of CTBT verification technologies. These exercises should help to evaluate the effectiveness of analysis procedures applied at NDCs and the quality, completeness and usefulness of IDC products for example. The exercise trigger of NPE2013 is a combination of a tempo-spatial indication pointing to a certain waveform event and simulated radionuclide concentrations generated by forward Atmospheric Transport Modelling based on a fictitious release. For the waveform event the date (4 Sept. 2013) is given and the region is communicated in a map showing the fictitious state of "Frisia" at the Coast of the North Sea in Central Europe. The potential connection between the waveform and radionuclide evidence remains unclear for exercise participants. The verification task was to identify the waveform event and to investigate potential sources of the radionuclide findings. The final question was whether the findings are CTBT relevant and justify a request for On-Site-Inspection in "Frisia". The seismic event was not included in the Reviewed Event Bulletin (REB) of the IDC. The available detections from the closest seismic IMS stations lead to a epicenter accuracy of about 24 km which is not sufficient to specify the 1000 km2 inspection area in case of an OSI. With use of data from local stations and adjusted velocity models the epicenter accuracy could be improved to less than 2 km, which demonstrates the crucial role of national technical means for verification tasks. The seismic NPE2013 event could be identified as induced from natural gas production in the source region. Similar waveforms and comparable spectral characteristic as a set of events in the same region are clear indications. The scenario of a possible treaty violation at the location of the seismic NPE2013 event could be disproved.
Recent development of infrasound monitoring network in Romania
NASA Astrophysics Data System (ADS)
Ghica, Daniela; Popa, Mihaela; Ionescu, Constantin
2017-04-01
The second half of 2016 was marked at National Institute for Earth Physics (NIEP) by a significant development of infrasound monitoring infrastructure in Romania. In addition to IPLOR, the 6-element acoustic array installed at Plostina, in the central part of Romania, since 2009, two other four-element arrays were deployed. The first one, BURARI infrasound research array, was deployed in late July 2016, under a joint effort of AFTAC, USA and NIEP, in the northern part of Romania, in Bucovina region. The sites, placed in vicinity of the central elements of BURAR seismic array (over 1.2 km aperture), are equipped with Chaparral Physics Model 21 microbarometers and Reftek RT 130 data loggers. The data, used mainly for research purposes within the scientific collaboration project between NIEP and AFTAC, are available to scientific community. The second one is a PTS portable infrasound array (I67RO) deployed for one year, starting with the end of September 2016, within a collaboration project between NIEP and PTS of the Preparatory Commission for CTBTO. This array is located in the western part of Romania, at Marisel, Cluj County, covering a 0.9 km aperture and being equipped with CEA/DAM MB2005 microbarometers and Reftek RT 130 data loggers. This joint experiment aims to contribute both to advanced understanding of infrasound sources in Central-Europe and to ARISE design study project, as an expansion of the spatial coverage of the European infrasound network. The data recorded by the three infrasound arrays deployed in Romania, during a same time interval (October - December 2016) were processed into detection arrival bulletins applying CEA/DASE PMCC algorithm embedded in DTK-GPMCC (extended CTBTO NDC-in-a-box) and WinPMCC software applications. The results were plotted and analyzed using DTK-DIVA software (extended CTBTO NDC-in-a-box), in order to assess detectability of each station, as well as the capacity of fusing detections into support of infrasound monitoring activity at NIEP. We present infrasound signals generated by an impulsive event (accidental explosion of a train carrying liquid petroleum gas in Hitrino, Bulgaria) recorded on these three arrays. The features calculated for the arrivals detected (backazimuth, arrival time, frequency and celerity) are used to associate signals with event and observe individually array performance.
45 CFR 80.12 - Effect on other regulations; forms and instructions.
Code of Federal Regulations, 2010 CFR
2010-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.12 Effect on other regulations; forms and... this Department. (Sec. 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d-10)) [29 FR 16298... instructions. 80.12 Section 80.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...
45 CFR 80.12 - Effect on other regulations; forms and instructions.
Code of Federal Regulations, 2012 CFR
2012-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.12 Effect on other regulations; forms and... this Department. (Sec. 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d-10)) [29 FR 16298... instructions. 80.12 Section 80.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...
45 CFR 80.12 - Effect on other regulations; forms and instructions.
Code of Federal Regulations, 2011 CFR
2011-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.12 Effect on other regulations; forms and... this Department. (Sec. 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d-10)) [29 FR 16298... instructions. 80.12 Section 80.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...
45 CFR 80.12 - Effect on other regulations; forms and instructions.
Code of Federal Regulations, 2013 CFR
2013-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.12 Effect on other regulations; forms and... this Department. (Sec. 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d-10)) [29 FR 16298... instructions. 80.12 Section 80.12 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION...
45 CFR 80.12 - Effect on other regulations; forms and instructions.
Code of Federal Regulations, 2014 CFR
2014-10-01
... EFFECTUATION OF TITLE VI OF THE CIVIL RIGHTS ACT OF 1964 § 80.12 Effect on other regulations; forms and... this Department. (Sec. 602, Civil Rights Act of 1964, 78 Stat. 252 (42 U.S.C. 2000d-10)) [29 FR 16298... instructions. 80.12 Section 80.12 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION...
The Complexity of Human Walking: A Knee Osteoarthritis Study
Kotti, Margarita; Duffell, Lynsey D.; Faisal, Aldo A.; McGregor, Alison H.
2014-01-01
This study proposes a framework for deconstructing complex walking patterns to create a simple principal component space before checking whether the projection to this space is suitable for identifying changes from the normality. We focus on knee osteoarthritis, the most common knee joint disease and the second leading cause of disability. Knee osteoarthritis affects over 250 million people worldwide. The motivation for projecting the highly dimensional movements to a lower dimensional and simpler space is our belief that motor behaviour can be understood by identifying a simplicity via projection to a low principal component space, which may reflect upon the underlying mechanism. To study this, we recruited 180 subjects, 47 of which reported that they had knee osteoarthritis. They were asked to walk several times along a walkway equipped with two force plates that capture their ground reaction forces along 3 axes, namely vertical, anterior-posterior, and medio-lateral, at 1000 Hz. Data when the subject does not clearly strike the force plate were excluded, leaving 1–3 gait cycles per subject. To examine the complexity of human walking, we applied dimensionality reduction via Probabilistic Principal Component Analysis. The first principal component explains 34% of the variance in the data, whereas over 80% of the variance is explained by 8 principal components or more. This proves the complexity of the underlying structure of the ground reaction forces. To examine if our musculoskeletal system generates movements that are distinguishable between normal and pathological subjects in a low dimensional principal component space, we applied a Bayes classifier. For the tested cross-validated, subject-independent experimental protocol, the classification accuracy equals 82.62%. Also, a novel complexity measure is proposed, which can be used as an objective index to facilitate clinical decision making. This measure proves that knee osteoarthritis subjects exhibit more variability in the two-dimensional principal component space. PMID:25232949
Turbulence Intensity at Inlet of 80- by 120-Foot Wind Tunnel Caused by Upwind Blockage
NASA Technical Reports Server (NTRS)
Salazar, Denise; Yuricich, Jillian
2014-01-01
In order to estimate the magnitude of turbulence in the National Full-Scale Aerodynamics Complex (NFAC) 80- by 120-Foot Wind Tunnel (80 x 120) caused by buildings located upwind from the 80 x 120 inlet, a 150th-scale study was performed that utilized a nominal two-dimensional blockage placed ahead of the inlet. The distance of the blockage ahead of the inlet was varied. This report describes velocity measurements made in the plane of the 80 x 120 model inlet for the case of zero ambient (atmospheric) wind.
Inferring genome-wide interplay landscape between DNA methylation and transcriptional regulation.
Tang, Binhua; Wang, Xin
2015-01-01
DNA methylation and transcriptional regulation play important roles in cancer cell development and differentiation processes. Based on the currently available cell line profiling information from the ENCODE Consortium, we propose a Bayesian inference model to infer and construct genome-wide interaction landscape between DNA methylation and transcriptional regulation, which sheds light on the underlying complex functional mechanisms important within the human cancer and disease context. For the first time, we select all the currently available cell lines (>=20) and transcription factors (>=80) profiling information from the ENCODE Consortium portal. Through the integration of those genome-wide profiling sources, our genome-wide analysis detects multiple functional loci of interest, and indicates that DNA methylation is cell- and region-specific, due to the interplay mechanisms with transcription regulatory activities. We validate our analysis results with the corresponding RNA-sequencing technique for those detected genomic loci. Our results provide novel and meaningful insights for the interplay mechanisms of transcriptional regulation and gene expression for the human cancer and disease studies.
Cloning of polymorphisms (COP): enrichment of polymorphic sequences from complex genomes
Li, Jingfeng; Wang, Fuli; Zabarovska, Veronika; Wahlestedt, Claes; Zabarovsky, Eugene R.
2000-01-01
Here we describe a new procedure (cloning of polymorphisms, COP) for enrichment of single nucleotide polymorphisms (SNPs) that represent restriction fragment length polymorphisms (RFLPs). COP would be applicable to the isolation of SNPs from particular regions of the genome, e.g. CpG islands, chromosomal bands, YACs or PAC contigs. A combination of digestion with restriction enzymes, treatment with uracil-DNA glycosylase and mung bean nuclease, PCR amplification and purification with streptavidin magnetic beads was used to isolate polymorphic sequences from the genomes of two human samples. After only two cycles of enrichment, 80% of the isolated clones were found to contain RFLPs. A simple method for the PCR detection of these polymorphisms was also developed. PMID:10606669
Totten, P A; Amsel, R; Hale, J; Piot, P; Holmes, K K
1982-01-01
New selective and differential human blood bilayer agar media with Tween 80 (HBT medium) or without Tween 80 (HB medium), developed for the isolation of Gardnerella (Haemophilus) vaginalis, permitted significantly higher G. vaginalis isolation rates than have been obtained for other media used for this purpose. HB medium consists of a basal layer of Columbia agar base containing colistin and naladixic acid with added amphotericin B and an overlayer of the same composition plus 5% human blood. HBT agar also contains Proteose Peptone No. 3 (Difco Laboratories) and Tween 80 in the basal layer and the overlayer. Both Tween 80 and the bilayer composition enhanced G. vaginalis production of human blood hemolysis, permitting detection of this organism even in the presence of heavy growth of other vaginal flora. The use of HB or HBT medium thus permitted the demonstration that G. vaginalis was present in vaginal fluid from a large percentage (up to 68%) of normal women. However, the concentration of G. vaginalis was found by semiquantitative analysis to be significantly higher in vaginal fluid from women with nonspecific vaginitis than in fluid from normal women. Images PMID:6764766
Code of Federal Regulations, 2012 CFR
2012-10-01
... CIVIL RIGHTS ACT OF 1964 § 80.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a..., insofar as this regulation is concerned, shall be made in accordance with § 80.10. (Sec. 602, Civil Rights... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING...
Code of Federal Regulations, 2013 CFR
2013-10-01
... CIVIL RIGHTS ACT OF 1964 § 80.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a..., insofar as this regulation is concerned, shall be made in accordance with § 80.10. (Sec. 602, Civil Rights... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING...
Code of Federal Regulations, 2011 CFR
2011-10-01
... CIVIL RIGHTS ACT OF 1964 § 80.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a..., insofar as this regulation is concerned, shall be made in accordance with § 80.10. (Sec. 602, Civil Rights... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING...
Code of Federal Regulations, 2010 CFR
2010-10-01
... CIVIL RIGHTS ACT OF 1964 § 80.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a..., insofar as this regulation is concerned, shall be made in accordance with § 80.10. (Sec. 602, Civil Rights... DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING...
Code of Federal Regulations, 2014 CFR
2014-10-01
... CIVIL RIGHTS ACT OF 1964 § 80.9 Hearings. (a) Opportunity for hearing. Whenever an opportunity for a..., insofar as this regulation is concerned, shall be made in accordance with § 80.10. (Sec. 602, Civil Rights... Department of Health and Human Services GENERAL ADMINISTRATION NONDISCRIMINATION UNDER PROGRAMS RECEIVING...
45 CFR 287.80 - What is the process for plan review and approval?
Code of Federal Regulations, 2010 CFR
2010-10-01
... Division of Tribal Services, Office of Community Services, Administration for Children and Families...? 287.80 Section 287.80 Public Welfare Regulations Relating to Public Welfare OFFICE OF FAMILY ASSISTANCE (ASSISTANCE PROGRAMS), ADMINISTRATION FOR CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN...
45 CFR 98.80 - General procedures and requirements.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 98.80 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Indian Tribes § 98.80 General procedures and requirements. An Indian Tribe or tribal... programs for the purpose of increasing the availability, affordability, and quality of child care and...
45 CFR 98.80 - General procedures and requirements.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 98.80 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Indian Tribes § 98.80 General procedures and requirements. An Indian Tribe or tribal... programs for the purpose of increasing the availability, affordability, and quality of child care and...
45 CFR 98.80 - General procedures and requirements.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 98.80 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Indian Tribes § 98.80 General procedures and requirements. An Indian Tribe or tribal... programs for the purpose of increasing the availability, affordability, and quality of child care and...
45 CFR 98.80 - General procedures and requirements.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 98.80 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CHILD CARE AND DEVELOPMENT FUND Indian Tribes § 98.80 General procedures and requirements. An Indian Tribe or tribal... programs for the purpose of increasing the availability, affordability, and quality of child care and...
47 CFR 80.227 - Special requirements for protection from RF radiation.
Code of Federal Regulations, 2012 CFR
2012-10-01
... radiation. 80.227 Section 80.227 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... requirements for protection from RF radiation. As part of the information provided with transmitters for ship... help prevent human exposure to radiofrequency (RF) radiation in excess of the RF exposure guidelines...
47 CFR 80.227 - Special requirements for protection from RF radiation.
Code of Federal Regulations, 2013 CFR
2013-10-01
... radiation. 80.227 Section 80.227 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... requirements for protection from RF radiation. As part of the information provided with transmitters for ship... help prevent human exposure to radiofrequency (RF) radiation in excess of the RF exposure guidelines...
47 CFR 80.227 - Special requirements for protection from RF radiation.
Code of Federal Regulations, 2011 CFR
2011-10-01
... radiation. 80.227 Section 80.227 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... requirements for protection from RF radiation. As part of the information provided with transmitters for ship... help prevent human exposure to radiofrequency (RF) radiation in excess of the RF exposure guidelines...
47 CFR 80.227 - Special requirements for protection from RF radiation.
Code of Federal Regulations, 2014 CFR
2014-10-01
... radiation. 80.227 Section 80.227 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... requirements for protection from RF radiation. As part of the information provided with transmitters for ship... help prevent human exposure to radiofrequency (RF) radiation in excess of the RF exposure guidelines...
42 CFR 409.80 - Inpatient deductible and coinsurance: General provisions.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 42 Public Health 2 2010-10-01 2010-10-01 false Inpatient deductible and coinsurance: General provisions. 409.80 Section 409.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES MEDICARE PROGRAM HOSPITAL INSURANCE BENEFITS Hospital Insurance Deductibles and...
47 CFR 80.227 - Special requirements for protection from RF radiation.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 47 Telecommunication 5 2010-10-01 2010-10-01 false Special requirements for protection from RF radiation. 80.227 Section 80.227 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... help prevent human exposure to radiofrequency (RF) radiation in excess of the RF exposure guidelines...
Lakshminarasimhan, Mahadevan; Boanca, Gina; Banks, Charles A. S.; Hattem, Gaye L.; Gabriel, Ana E.; Groppe, Brad D.; Smoyer, Christine; Malanowski, Kate E.; Peak, Allison; Florens, Laurence; Washburn, Michael P.
2016-01-01
The highly conserved yeast R2TP complex, consisting of Rvb1, Rvb2, Pih1, and Tah1, participates in diverse cellular processes ranging from assembly of protein complexes to apoptosis. Rvb1 and Rvb2 are closely related proteins belonging to the AAA+ superfamily and are essential for cell survival. Although Rvbs have been shown to be associated with various protein complexes including the Ino80 and Swr1chromatin remodeling complexes, we performed a systematic quantitative proteomic analysis of their associated proteins and identified two additional complexes that associate with Rvb1 and Rvb2: the chaperonin-containing T-complex and the 19S regulatory particle of the proteasome complex. We also analyzed Rvb1 and Rvb2 purified from yeast strains devoid of PIH1 and TAH1. These analyses revealed that both Rvb1 and Rvb2 still associated with Hsp90 and were highly enriched with RNA polymerase II complex components. Our analyses also revealed that both Rvb1 and Rvb2 were recruited to the Ino80 and Swr1 chromatin remodeling complexes even in the absence of Pih1 and Tah1 proteins. Using further biochemical analysis, we showed that Rvb1 and Rvb2 directly interacted with Hsp90 as well as with the RNA polymerase II complex. RNA-Seq analysis of the deletion strains compared with the wild-type strains revealed an up-regulation of ribosome biogenesis and ribonucleoprotein complex biogenesis genes, down-regulation of response to abiotic stimulus genes, and down-regulation of response to temperature stimulus genes. A Gene Ontology analysis of the 80 proteins whose protein associations were altered in the PIH1 or TAH1 deletion strains found ribonucleoprotein complex proteins to be the most enriched category. This suggests an important function of the R2TP complex in ribonucleoprotein complex biogenesis at both the proteomic and genomic levels. Finally, these results demonstrate that deletion network analyses can provide novel insights into cellular systems. PMID:26831523
Salcedo, Jaime; Gormaz, Maria; López-Mendoza, Maria C; Nogarotto, Elisabetta; Silvestre, Dolores
2015-04-01
Lyophilization appears to be a viable method for storing human milk, assuring no microbiological contamination and preserving its health benefits and antibacterial properties. The aim of the study is to evaluate and compare the effects of different storage methods (lyophilization and freezing at -20°C and -80°C) and maternal factors (gestational length or time postpartum) upon the microbiological contents and bactericidal activity of human milk. The possible relation between bactericidal activity and the content of certain nutrients and functional components is also investigated. Microbiological content, bactericidal activity, sialic acid, and ganglioside contents, as well as protein, fat, and lactose concentrations were assessed in 125 human milk samples from 65 healthy donors in the Human Milk Bank of La Fe (Valencia, Spain). Lyophilization and storage at -80°C significantly reduced the content of mesophilic aerobic microorganisms and Staphylococcus epidermidis when compared with storage at -20°C. Bactericidal activity was not significantly modified by lyophilization when compared with freezing at either -20°C or -80°C. Bactericidal activity was not correlated with fat, protein, or lactose content, but was significantly correlated to ganglioside content. The bactericidal activity was significantly greater (P < 0.05) in mature milk and in milk from women with term delivery than in milk from early lactation (days 1-7 postpartum) and milk from women with preterm delivery, respectively. Lyophilization and storage at -80°C of human milk yields similar results and are superior to storage at -20C with regard to microbial and bactericidal capacities, being a feasible alternative for human milk banks.
Molecular Basis for Phosphorylation-dependent SUMO Recognition by the DNA Repair Protein RAP80.
Anamika; Spyracopoulos, Leo
2016-02-26
Recognition and repair of double-stranded DNA breaks (DSB) involves the targeted recruitment of BRCA tumor suppressors to damage foci through binding of both ubiquitin (Ub) and the Ub-like modifier SUMO. RAP80 is a component of the BRCA1 A complex, and plays a key role in the recruitment process through the binding of Lys(63)-linked poly-Ub chains by tandem Ub interacting motifs (UIM). RAP80 also contains a SUMO interacting motif (SIM) just upstream of the tandem UIMs that has been shown to specifically bind the SUMO-2 isoform. The RAP80 tandem UIMs and SIM function collectively for optimal recruitment of BRCA1 to DSBs, although the molecular basis of this process is not well understood. Using NMR spectroscopy, we demonstrate that the RAP80 SIM binds SUMO-2, and that both specificity and affinity are enhanced through phosphorylation of the canonical CK2 site within the SIM. The affinity increase results from an enhancement of electrostatic interactions between the phosphoserines of RAP80 and the SIM recognition module within SUMO-2. The NMR structure of the SUMO-2·phospho-RAP80 complex reveals that the molecular basis for SUMO-2 specificity is due to isoform-specific sequence differences in electrostatic SIM recognition modules. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Bdf1 Bromodomains Are Essential for Meiosis and the Expression of Meiotic-Specific Genes
Perot, Jonathan; Arlotto, Marie; Mietton, Flore; Boland, Anne; Deleuze, Jean-François; Ferro, Myriam; Govin, Jérôme
2017-01-01
Bromodomain and Extra-terminal motif (BET) proteins play a central role in transcription regulation and chromatin signalling pathways. They are present in unicellular eukaryotes and in this study, the role of the BET protein Bdf1 has been explored in Saccharomyces cerevisiae. Mutation of Bdf1 bromodomains revealed defects on both the formation of spores and the meiotic progression, blocking cells at the exit from prophase, before the first meiotic division. This phenotype is associated with a massive deregulation of the transcription of meiotic genes and Bdf1 bromodomains are required for appropriate expression of the key meiotic transcription factor NDT80 and almost all the Ndt80-inducible genes, including APC complex components. Bdf1 notably accumulates on the promoter of Ndt80 and its recruitment is dependent on Bdf1 bromodomains. In addition, the ectopic expression of NDT80 during meiosis partially bypasses this dependency. Finally, purification of Bdf1 partners identified two independent complexes with Bdf2 or the SWR complex, neither of which was required to complete sporulation. Taken together, our results unveil a new role for Bdf1 –working independently from its predominant protein partners Bdf2 and the SWR1 complex–as a regulator of meiosis-specific genes. PMID:28068333
21 CFR 500.80 - Scope of this subpart.
Code of Federal Regulations, 2010 CFR
2010-04-01
... Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Scope of this subpart. 500.80 Section 500.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL...
42 CFR 460.80 - Fiscal soundness.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 42 Public Health 4 2011-10-01 2011-10-01 false Fiscal soundness. 460.80 Section 460.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE...
42 CFR 460.80 - Fiscal soundness.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 42 Public Health 4 2010-10-01 2010-10-01 false Fiscal soundness. 460.80 Section 460.80 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE...
21 CFR 336.80 - Professional labeling.
Code of Federal Regulations, 2010 CFR
2010-04-01
... labeling. The labeling provided to health professionals (but not to the general public) may contain the... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Professional labeling. 336.80 Section 336.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...
21 CFR 349.80 - Professional labeling.
Code of Federal Regulations, 2010 CFR
2010-04-01
... labeling. The labeling of any OTC ophthalmic demulcent drug product provided to health professionals (but... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Professional labeling. 349.80 Section 349.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR...
42 CFR 102.80 - Calculation of medical benefits.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 42 Public Health 1 2013-10-01 2013-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...
42 CFR 102.80 - Calculation of medical benefits.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 42 Public Health 1 2012-10-01 2012-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...
42 CFR 102.80 - Calculation of medical benefits.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 42 Public Health 1 2014-10-01 2014-10-01 false Calculation of medical benefits. 102.80 Section 102.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX... medical items and services that are reasonable and necessary to diagnose or treat a smallpox vaccine...
42 CFR 84.80 - Interchangeability of oxygen and air prohibited.
Code of Federal Regulations, 2011 CFR
2011-10-01
... 42 Public Health 1 2011-10-01 2011-10-01 false Interchangeability of oxygen and air prohibited. 84.80 Section 84.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...
42 CFR 84.80 - Interchangeability of oxygen and air prohibited.
Code of Federal Regulations, 2010 CFR
2010-10-01
... 42 Public Health 1 2010-10-01 2010-10-01 false Interchangeability of oxygen and air prohibited. 84.80 Section 84.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...
42 CFR 84.80 - Interchangeability of oxygen and air prohibited.
Code of Federal Regulations, 2012 CFR
2012-10-01
... 42 Public Health 1 2012-10-01 2012-10-01 false Interchangeability of oxygen and air prohibited. 84.80 Section 84.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...
42 CFR 84.80 - Interchangeability of oxygen and air prohibited.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 42 Public Health 1 2014-10-01 2014-10-01 false Interchangeability of oxygen and air prohibited. 84.80 Section 84.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...
42 CFR 84.80 - Interchangeability of oxygen and air prohibited.
Code of Federal Regulations, 2013 CFR
2013-10-01
... 42 Public Health 1 2013-10-01 2013-10-01 false Interchangeability of oxygen and air prohibited. 84.80 Section 84.80 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES OCCUPATIONAL SAFETY AND HEALTH RESEARCH AND RELATED ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self...
21 CFR 110.80 - Processes and controls.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Processes and controls. 110.80 Section 110.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... extraneous-material testing procedures shall be used where necessary to identify sanitation failures or...
21 CFR 110.80 - Processes and controls.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Processes and controls. 110.80 Section 110.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... extraneous-material testing procedures shall be used where necessary to identify sanitation failures or...
21 CFR 110.80 - Processes and controls.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Processes and controls. 110.80 Section 110.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... extraneous-material testing procedures shall be used where necessary to identify sanitation failures or...
Nonlocal atlas-guided multi-channel forest learning for human brain labeling
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ma, Guangkai; Gao, Yaozong; Wu, Guorong
Purpose: It is important for many quantitative brain studies to label meaningful anatomical regions in MR brain images. However, due to high complexity of brain structures and ambiguous boundaries between different anatomical regions, the anatomical labeling of MR brain images is still quite a challenging task. In many existing label fusion methods, appearance information is widely used. However, since local anatomy in the human brain is often complex, the appearance information alone is limited in characterizing each image point, especially for identifying the same anatomical structure across different subjects. Recent progress in computer vision suggests that the context features canmore » be very useful in identifying an object from a complex scene. In light of this, the authors propose a novel learning-based label fusion method by using both low-level appearance features (computed from the target image) and high-level context features (computed from warped atlases or tentative labeling maps of the target image). Methods: In particular, the authors employ a multi-channel random forest to learn the nonlinear relationship between these hybrid features and target labels (i.e., corresponding to certain anatomical structures). Specifically, at each of the iterations, the random forest will output tentative labeling maps of the target image, from which the authors compute spatial label context features and then use in combination with original appearance features of the target image to refine the labeling. Moreover, to accommodate the high inter-subject variations, the authors further extend their learning-based label fusion to a multi-atlas scenario, i.e., they train a random forest for each atlas and then obtain the final labeling result according to the consensus of results from all atlases. Results: The authors have comprehensively evaluated their method on both public LONI-LBPA40 and IXI datasets. To quantitatively evaluate the labeling accuracy, the authors use the dice similarity coefficient to measure the overlap degree. Their method achieves average overlaps of 82.56% on 54 regions of interest (ROIs) and 79.78% on 80 ROIs, respectively, which significantly outperform the baseline method (random forests), with the average overlaps of 72.48% on 54 ROIs and 72.09% on 80 ROIs, respectively. Conclusions: The proposed methods have achieved the highest labeling accuracy, compared to several state-of-the-art methods in the literature.« less
Nonlocal atlas-guided multi-channel forest learning for human brain labeling
Ma, Guangkai; Gao, Yaozong; Wu, Guorong; Wu, Ligang; Shen, Dinggang
2016-01-01
Purpose: It is important for many quantitative brain studies to label meaningful anatomical regions in MR brain images. However, due to high complexity of brain structures and ambiguous boundaries between different anatomical regions, the anatomical labeling of MR brain images is still quite a challenging task. In many existing label fusion methods, appearance information is widely used. However, since local anatomy in the human brain is often complex, the appearance information alone is limited in characterizing each image point, especially for identifying the same anatomical structure across different subjects. Recent progress in computer vision suggests that the context features can be very useful in identifying an object from a complex scene. In light of this, the authors propose a novel learning-based label fusion method by using both low-level appearance features (computed from the target image) and high-level context features (computed from warped atlases or tentative labeling maps of the target image). Methods: In particular, the authors employ a multi-channel random forest to learn the nonlinear relationship between these hybrid features and target labels (i.e., corresponding to certain anatomical structures). Specifically, at each of the iterations, the random forest will output tentative labeling maps of the target image, from which the authors compute spatial label context features and then use in combination with original appearance features of the target image to refine the labeling. Moreover, to accommodate the high inter-subject variations, the authors further extend their learning-based label fusion to a multi-atlas scenario, i.e., they train a random forest for each atlas and then obtain the final labeling result according to the consensus of results from all atlases. Results: The authors have comprehensively evaluated their method on both public LONI_LBPA40 and IXI datasets. To quantitatively evaluate the labeling accuracy, the authors use the dice similarity coefficient to measure the overlap degree. Their method achieves average overlaps of 82.56% on 54 regions of interest (ROIs) and 79.78% on 80 ROIs, respectively, which significantly outperform the baseline method (random forests), with the average overlaps of 72.48% on 54 ROIs and 72.09% on 80 ROIs, respectively. Conclusions: The proposed methods have achieved the highest labeling accuracy, compared to several state-of-the-art methods in the literature. PMID:26843260
29 CFR 1601.80 - Certified designated FEP agencies.
Code of Federal Regulations, 2013 CFR
2013-07-01
... Commission Madison Equal Opportunity Commission Maine Human Rights Commission Maryland Commission on Human... Commission West Virginia Human Rights Commission Wisconsin Equal Rights Division, Department of Industry...
29 CFR 1601.80 - Certified designated FEP agencies.
Code of Federal Regulations, 2012 CFR
2012-07-01
... Commission Madison Equal Opportunity Commission Maine Human Rights Commission Maryland Commission on Human... Commission West Virginia Human Rights Commission Wisconsin Equal Rights Division, Department of Industry...
29 CFR 1601.80 - Certified designated FEP agencies.
Code of Federal Regulations, 2014 CFR
2014-07-01
... Commission Madison Equal Opportunity Commission Maine Human Rights Commission Maryland Commission on Human... Commission West Virginia Human Rights Commission Wisconsin Equal Rights Division, Department of Industry...
Sarria, André Lucio Franceschini; Vilela, Adriana Ferreira Lopes; Frugeri, Bárbara Mammana; Fernandes, João Batista; Carlos, Rose Maria; da Silva, Maria Fátima das Graças Fernandes; Cass, Quezia Bezerra; Cardoso, Carmen Lúcia
2016-11-01
Metal chelates strongly influence the nature and magnitude of pharmacological activities in flavonoids. In recent years, studies have shown that a promising class of flavanone-metal ion complexes can act as selective cholinesterase inhibitors (ChEIs), which has led our group to synthesize a new series of flavanone derivatives (hesperidin, hesperetin, naringin, and naringenin) complexed to either copper (II) or zinc (II) and to evaluate their potential use as selective ChEIs. Most of the synthesized complexes exhibited greater inhibitory activity against acetylcholinesterase (AChE) than against butyrylcholinesterase (BChE). Nine of these complexes constituted potent, reversible, and selective ChEIs with inhibitory potency (IC 50 ) and inhibitory constant (K i ) ranging from 0.02 to 4.5μM. Copper complexes with flavanone-bipyridine derivatives afforded the best inhibitory activity against AChE and BChE. The complex Cu(naringin)(2,2'-bipyridine) (11) gave IC 50 and K i values of 0.012±0.002 and 0.07±0.01μM for huAChE, respectively, which were lower than the inhibitory values obtained for standard galanthamine (IC 50 =206±30.0 and K i =126±18.0μM). Evaluation of the inhibitory activity of this complex against butyrylcholinesterase from human serum (huBChE) gave IC 50 and K i values of 8.0±1.4 and 2.0±0.1μM, respectively. A Liquid Chromatography-Immobilized Capillary Enzyme Reactor by UV detection (LC-ICER-UV) assay allowed us to determine the IC 50 and K i values and the type of mechanism for the best inhibitors. Copyright © 2016 Elsevier Inc. All rights reserved.
Development of a human-specific B. thetaiotaomicron IMS ...
Immunomagnetic separation/adenosine triphosphate (IMS/ATP) assays utilize paramagnetic beads and target-specific antibodies to isolate target organisms. Following isolation, adenosine tri-phosphate (ATP) is extracted from the target population and quantified. An inversely-coupled (Inv-IMS/ATP)assay for detection of Bacteroides thetaiotaomicron was developed and applied for rapid detection of human-associated fecal contamination in surface waters in Baja California. Specificity of the assay was tested against challenge solutions of varying concentrations of dog, gull, horse and chicken feces, and a field validation survey of coastal and WWTP effluent water quality in Rosarito and Enseneda, Baja California was conducted. Inv IMS/ATP measurements made shown to be specific and sensitive to human fecal contamination. At test concentrations of less than 1000 MPN ENT/100 mL, sensitivity and specificity of the assay both exceeded 80%. Moreover, the Inv-IMS/ATP assay yielded measurements of viable B. thetaiotaomicron that were comparable to the HF183 human marker in complex surface waters impacted with both wastewater and runoff, and the Inv-IMS/ATP assay was able to effectively differentiate between surface waters impacted with adequately and inadequately treated wastewater. The Inv-IMS/ATP assays shows promise for rapid evaluation of recreational water quality in areas where access to more expensive methods is limited and in areas where water quality in unpredicta
NASA Astrophysics Data System (ADS)
Li, Caiyun; Wei, Huajiang; Zhao, Yanping; Wu, Guoyong; Gu, Huaimin; Guo, Zhouyi; Yang, Hongqin; He, Yonghong; Xie, Shusen
2018-07-01
The purpose of this study is to illustrate experimentally the optical coherence tomography (OCT) signal slope and diffuse reflectance (DR) spectra of 30% and 80% glycerol combined with electroporation (EP) diffusion in normal, benign and cancerous human gastric tissues in vitro. The results of OCT showed that the permeability coefficients of 80% and 30% glycerol (both with and without EP) have the following trend: human cancerous gastric tissue > human benign gastric tissue > human normal gastric tissue under the same conditions. The permeability coefficient of the 30% glycerol group is larger than that of the 80% glycerol group under the same circumstances; the permeability coefficient of glycerol combined with the EP group is larger than that without the EP group under the same conditions. The permeability coefficient and the reduction of the DR spectra have perfect linear correlation (R2 = 0.9745). The research results suggest that OCT and the DR spectra combined with an optical clearing agent (glycerol) and the EP method can potentially become a powerful tool for the early diagnosis and monitoring of human gastric cancer.
Akbari, Majid; Bakhshi, Bita; Najar Peerayeh, Shahin
2016-01-01
Based on biochemical properties, Enterobacter cloacae represents a large complex of at least 13 variant species, subspecies, and genotypes that progressively identified as the most species causing hospital-acquired infections. The aim of this study was to determine the relevance between phylogenetically related strains within the E. cloacae complex and the frequency of urinary tract infection caused by them. A 268-bp fragment was obtained from hsp60 gene for 50 clinical E. cloacae isolates from urine cultures of inpatients that admitted to six hospitals in Tehran, Iran during December 2012 to November 2013. The 107 nucleotide sequences were analyzed and the evolutionary distances of sequences were computed and neighbor-joining tree was calculated. It showed that all of the genetic clusters have not an equal involvement in pathogenesis of urinary tract infections. Three superior clusters were found, together representing more than two third (80%) of the isolates (cluster VI with 25 members; clusters III and VIII with 9 and 6 members, respectively) and some genetic clusters were absent (IV, X, XII, and xiii), some of which are supposed to be associated with plants and no human infection has been reported. This study, for the first time, reports the unequal contribution of E. cloacae complex subspecies and clusters in urinary tract infections in Iran and together with studies from other countries suggest that the subspecies of E.hormaechei subsp. Oharae is the most prevalent E. cloacae complex subspecies regardless of country under study.
Martínez-Salazar, Martha; López-Urrutia, Eduardo; Arechaga-Ocampo, Elena; Bonilla-Moreno, Raul; Martínez-Castillo, Macario; Díaz-Hernández, Job; Del Moral-Hernández, Oscar; Cedillo-Barrón, Leticia; Martines-Juarez, Víctor; De Nova-Ocampo, Monica; Valdes, Jesús; Berumen, Jaime; Villegas-Sepúlveda, Nicolás
2014-12-05
The human papillomavirus type 16 (HPV-16) E6/E7 spliced transcripts are heterogeneously expressed in cervical carcinoma. The heterogeneity of the E6/E7 splicing profile might be in part due to the intrinsic variation of splicing factors in tumor cells. However, the splicing factors that bind the E6/E7 intron 1 (In-1) have not been defined. Therefore, we aimed to identify these factors; we used HeLa nuclear extracts (NE) for in vitro spliceosome assembly. The proteins were allowed to bind to an RNA/DNA hybrid formed by the In-1 transcript and a 5'-biotinylated DNA oligonucleotide complementary to the upstream exon sequence, which prevented interference in protein binding to the intron. The hybrid probes bound with the nuclear proteins were coupled to streptavidin magnetic beads for chromatography affinity purification. Proteins were eluted and identified by mass spectrometry (MS). Approximately 170 proteins were identified by MS, 80% of which were RNA binding proteins, including canonical spliceosome core components, helicases and regulatory splicing factors. The canonical factors were identified as components of the spliceosomal B-complex. Although 35-40 of the identified factors were cognate splicing factors or helicases, they have not been previously detected in spliceosome complexes that were assembled using in vivo or in vitro models. Copyright © 2014 Elsevier B.V. All rights reserved.
80. DETAIL OF TYPICAL PRESSURE GAUGE IN NITROGEN AND HELIUM ...
80. DETAIL OF TYPICAL PRESSURE GAUGE IN NITROGEN AND HELIUM STORAGE AND TRANSFER CONTROL SKIDS ON NORTH END OF SLC-3W FUEL APRON - Vandenberg Air Force Base, Space Launch Complex 3, Launch Pad 3 West, Napa & Alden Roads, Lompoc, Santa Barbara County, CA
Stopa, E G; Koh, E T; Svendsen, C N; Rogers, W T; Schwaber, J S; King, J C
1991-06-01
Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.
21 CFR 226.80 - Packaging and labeling.
Code of Federal Regulations, 2014 CFR
2014-04-01
... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...
21 CFR 226.80 - Packaging and labeling.
Code of Federal Regulations, 2013 CFR
2013-04-01
... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...
21 CFR 226.80 - Packaging and labeling.
Code of Federal Regulations, 2012 CFR
2012-04-01
... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...
21 CFR 226.80 - Packaging and labeling.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...
21 CFR 80.38 - Treatment of batch after certification.
Code of Federal Regulations, 2011 CFR
2011-04-01
... person requesting certification may use such color additive for the purpose of coloring a food, drug, or... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Treatment of batch after certification. 80.38 Section 80.38 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...
21 CFR 80.38 - Treatment of batch after certification.
Code of Federal Regulations, 2010 CFR
2010-04-01
... person requesting certification may use such color additive for the purpose of coloring a food, drug, or... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Treatment of batch after certification. 80.38 Section 80.38 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL...
21 CFR 226.80 - Packaging and labeling.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Packaging and labeling. 226.80 Section 226.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... Type A medicated article(s) with lot or control numbers that permit determination of the history of the...
21 CFR 80.10 - Fees for certification services.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Fees for certification services. 80.10 Section 80.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL COLOR...) Method of payment. All deposits and fees required by this section shall be paid by money order, bank...
21 CFR 820.80 - Receiving, in-process, and finished device acceptance.
Code of Federal Regulations, 2011 CFR
2011-04-01
... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Receiving, in-process, and finished device acceptance. 820.80 Section 820.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria...
21 CFR 820.80 - Receiving, in-process, and finished device acceptance.
Code of Federal Regulations, 2010 CFR
2010-04-01
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Receiving, in-process, and finished device acceptance. 820.80 Section 820.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria...
Karmakar, Souvik; Zhang, Weidong; Ahmad, Gul; Torben, Workineh; Alam, Mayeen U.; Le, Loc; Damian, Raymond T.; Wolf, Roman F.; White, Gary L.; Carey, David W.; Carter, Darrick; Reed, Steven G.; Siddiqui, Afzal A.
2014-01-01
No vaccines are available for human use for any parasitic infections, including the helminthic disease schistosomiasis. Sm-p80, the large subunit of Schistosoma mansoni calpain, is a leading antigen candidate for a schistosomiasis vaccine. Prophylactic and antifecundity efficacies of Sm-p80 have been tested using a variety of vaccine approaches in both rodent and nonhuman primate models. However, the therapeutic efficacy of a Sm-p80–based vaccine had not been determined. In this study, we evaluated the therapeutic efficacy of Sm-p80 by using 2 different strategies and 3 Sm-p80–based vaccine formulations in baboons. Vaccine formulations were able to decrease established adult worms by 10%–36%, reduce retention of eggs in tissues by 10%–57%, and decrease egg excretion in feces by 13%–33%, compared with control formulations. Marked differences were observed in B and T cell immune correlates between vaccinated and control animals. This is the first report of killing of established adult schistosome worms by a vaccine. In addition to distinct prophylactic efficacy of Sm-p80, this study adds to the evidence that Sm-p80 is a potentially important antigen with both substantial prophylactic and therapeutic efficacies. These data reinforce that Sm-p80 should be moved forward along the path toward human clinical trials. PMID:24436452
NASA Astrophysics Data System (ADS)
Salem, A. A.
2006-09-01
New sensitive, reliable and reproducible fluorimetric methods for determining microgram amounts of nucleic acids based on their reactions with Fe(II), Os(III) or Sm(III) complexes of 4,7-diphenyl-1,10-phenanthroline are proposed. Two complementary single stranded synthetic DNA sequences based on calf thymus as well as their hybridized double stranded were used. Nucleic acids were found to react instantaneously at room temperature in Tris-Cl buffer pH 7, with the investigated complexes resulting in decreasing their fluorescence emission. Two fluorescence peaks around 388 and 567 nm were obtained for the three complexes using excitation λmax of 280 nm and were used for this investigation. Linear calibration graphs in the range 1-6 μg/ml were obtained. Detection limits of 0.35-0.98 μg/ml were obtained. Using the calibration graphs for the synthetic dsDNA, relative standard deviations of 2.0-5.0% were obtained for analyzing DNA in the extraction products from calf thymus and human blood. Corresponding Recovery% of 80-114 were obtained. Student's t-values at 95% confidence level showed insignificant difference between the real and measured values. Results obtained by these methods were compared with the ethidium bromide method using the F-test and satisfactory results were obtained. The association constants and number of binding sites of synthetic ssDNA and dsDNA with the three complexes were estimated using Rosenthanl graphic method. The interaction mechanism was discussed and an intercalation mechanism was suggested for the binding reaction between nucleic acids and the three complexes.
Jhan, J-K; Chung, Y-C; Chen, G-H; Chang, C-H; Lu, Y-C; Hsu, C-K
2016-06-01
The seed coat of black soya bean (SCBS) contains high amount of anthocyanins and shows antioxidant and anti-mushroom tyrosinase activities. The objectives of this study were to analyse the anthocyanins in SCBS with different solvents and to find the relationship between anthocyanin profile with anti-human and anti-mushroom tyrosinase activities. SCBS was extracted with hot water, 50 and 80% ethanol, 50 and 80% acetone and 50 and 80% acidified acetone. Total phenol and total flavonoid contents in the extracts were determined. Anthocyanins in the extracts were analysed using HPLC and LC/MS/MS. A genetically engineered human tyrosinase was used to evaluate the anti-tyrosinase potential of the extracts from SCBS. 80% acetone extract from SCBS obtained the highest total phenol, total flavonoid and cyanidin-3-O-glucoside (C3G) contents among all the extracts, whereas the hot water extract showed the lowest antioxidant contents. Three anthocyanin compounds were found in all the extracts from SCBS, and the analysis of HPLC and LC/MS/MS indicated that they were C3G, delphinidin-3-O-glucoside (D3G) and peonidin-3-O-glucoside (P3G). The ratios of C3G (2.84 mg g(-1) ), D3G (0.34 mg g(-1) ) and P3G (0.35 mg g(-1) ) in 80% acidified acetone extract were 76.6, 9.1 and 9.3%, respectively. All the extracts from SCBS possessed anti-human tyrosinase activity. Moreover, a good correlation was found between the anti-human tyrosinase activities and C3G contents in the extracts. Antioxidants in SCBS also possess anti-human and anti-mushroom tyrosinase activities. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.