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Sample records for 2a figure 2b

  1. Rf2a and rf2b transcription factors

    DOEpatents

    Beachy, Roger N.; Petruccelli, Silvana; Dai, Shunhong

    2007-10-02

    A method of activating the rice tungro bacilliform virus (RTBV) promoter in vivo is disclosed. The RTBV promoter is activated by exposure to at least one protein selected from the group consisting of Rf2a and Rf2b.

  2. INSAT-2A and 2B development mechanisms

    NASA Technical Reports Server (NTRS)

    Sathyanarayan, M. N.; Rao, M. Nageswara; Nataraju, B. S.; Viswanatha, N.; Chary, M. Laxmana; Balan, K. S.; Murthy, V. Sridhara; Aller, Raju; Kumar, H. N. Suresha

    1994-01-01

    The Indian National Satellite (INSAT) 2A and 2B have deployment mechanisms for deploying the solar array, two C/S band antenna reflectors and a coilable lattice boom with sail. The mechanisms have worked flawlessly on both satellites. The configuration details, precautions taken during the design phase, the test philosophy, and some of the critical analysis activities are discussed.

  3. Distinct roles of NR2A and NR2B cytoplasmic tails in long term potentiation

    PubMed Central

    Foster, Kelly A.; McLaughlin, Nathan; Edbauer, Dieter; Phillips, Marnie; Bolton, Andrew; Constantine-Paton, Martha; Sheng, Morgan

    2010-01-01

    NMDA receptors (NMDARs) are critical mediators of activity-dependent synaptic plasticity, but the differential roles of NR2A- versus NR2B-containing NMDARs have been controversial. Here, we investigate the roles of NR2A and NR2B in LTP in organotypic hippocampal slice cultures using RNAi and overexpression, to complement pharmacological approaches. In young slices, when NR2B is the predominant subunit expressed, LTP is blocked by the NR2B-selective antagonist Ro25-6981. As slices mature, and NR2A expression rises, activation of NR2B receptors became no longer necessary for LTP induction. LTP was blocked, however, by RNAi knockdown of NR2B, and this was rescued by coexpression of an RNAi-resistant NR2B (NR2B*) cDNA. Interestingly, a chimeric NR2B subunit in which the C-terminal cytoplasmic tail was replaced by that of NR2A failed to rescue LTP while the reverse chimera, NR2A channel with NR2B tail, was able to restore LTP. Thus expression of NR2B with its intact cytoplasmic tail is required for LTP induction, at an age when channel activity of NR2B-NMDARs is not required for LTP. Overexpression of wildtype NR2A failed to rescue LTP in neurons transfected with NR2B-RNAi construct, despite restoring NMDA-EPSC amplitude to a similar level as NR2B*. Surprisingly, an NR2A construct lacking its entire C-terminal cytoplasmic tail regained its ability to restore LTP. Together these data suggest that the NR2B subunit plays a critical role for LTP, presumably by recruiting relevant molecules important for LTP via its cytoplasmic tail. By contrast, NR2A is not essential for LTP and its cytoplasmic tail seems to carry inhibitory factors for LTP. PMID:20164351

  4. Solution structure of the isolated histone H2A-H2B heterodimer

    PubMed Central

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1–β1–α2–β2–α3–αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {1H}-15N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27–34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  5. Solution structure of the isolated histone H2A-H2B heterodimer.

    PubMed

    Moriwaki, Yoshihito; Yamane, Tsutomu; Ohtomo, Hideaki; Ikeguchi, Mitsunori; Kurita, Jun-Ichi; Sato, Masahiko; Nagadoi, Aritaka; Shimojo, Hideaki; Nishimura, Yoshifumi

    2016-01-01

    During chromatin-regulated processes, the histone H2A-H2B heterodimer functions dynamically in and out of the nucleosome. Although detailed crystal structures of nucleosomes have been established, that of the isolated full-length H2A-H2B heterodimer has remained elusive. Here, we have determined the solution structure of human H2A-H2B by NMR coupled with CS-Rosetta. H2A and H2B each contain a histone fold, comprising four α-helices and two β-strands (α1-β1-α2-β2-α3-αC), together with the long disordered N- and C-terminal H2A tails and the long N-terminal H2B tail. The N-terminal αN helix, C-terminal β3 strand, and 310 helix of H2A observed in the H2A-H2B nucleosome structure are disordered in isolated H2A-H2B. In addition, the H2A α1 and H2B αC helices are not well fixed in the heterodimer, and the H2A and H2B tails are not completely random coils. Comparison of hydrogen-deuterium exchange, fast hydrogen exchange, and {(1)H}-(15)N hetero-nuclear NOE data with the CS-Rosetta structure indicates that there is some conformation in the H2A 310 helical and H2B Lys11 regions, while the repression domain of H2B (residues 27-34) exhibits an extended string-like structure. This first structure of the isolated H2A-H2B heterodimer provides insight into its dynamic functions in chromatin. PMID:27181506

  6. Fabrication Report for the AFC-2A and AFC-2B Capsule Irradiations in the ATR

    SciTech Connect

    Timothy A. Hyde

    2007-10-01

    This document provides a general narrative description of the AFC-2A and 2B fuel fabrication processes for the AFC 2A and AFC 2B fuel irradiation experiments fabricated at the Idaho National Laboratory’s Materials and Fuels Complex (MFC) for irradiation in the Advanced Test Reactor (ATR).

  7. Pathogenesis of PCV2a and PCV2b virus in germ-free pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic analysis of porcine circovirus type 2 (PCV2) reveals 2 subgroups that will be referred to as PCV2a and PCV2b representing the North American and European prototypes respectfully. This paper summarizes 3 studies comparing the pathogenesis of 2a and 2b viruses in germ-free pigs. In this PCV2...

  8. Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly

    PubMed Central

    Kweon, Hae-Jin; Kim, Dong-Il; Bae, Yeonju; Park, Jae-Yong; Suh, Byung-Chang

    2016-01-01

    Acid-sensing ion channels (ASICs) are proton-activated cation channels that play important roles as typical proton sensors during pathophysiological conditions and normal synaptic activities. Among the ASIC subunits, ASIC2a and ASIC2b are alternative splicing products from the same gene, ACCN1. It has been shown that ASIC2 isoforms have differential subcellular distribution: ASIC2a targets the cell surface by itself, while ASIC2b resides in the ER. However, the underlying mechanism for this differential subcellular localization remained to be further elucidated. By constructing ASIC2 chimeras, we found that the first transmembrane (TM1) domain and the proximal post-TM1 domain (17 amino acids) of ASIC2a are critical for membrane targeting of the proteins. We also observed that replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b. We finally confirmed that ASIC2b is delivered to the cell surface from the ER by forming heteromers with ASIC2a, and that the N-terminal region of ASIC2a is additionally required for the ASIC2a-dependent membrane targeting of ASIC2b. Together, our study supports an important role of ASIC2a in membrane targeting of ASIC2b. PMID:27477936

  9. Acid-Sensing Ion Channel 2a (ASIC2a) Promotes Surface Trafficking of ASIC2b via Heteromeric Assembly.

    PubMed

    Kweon, Hae-Jin; Kim, Dong-Il; Bae, Yeonju; Park, Jae-Yong; Suh, Byung-Chang

    2016-01-01

    Acid-sensing ion channels (ASICs) are proton-activated cation channels that play important roles as typical proton sensors during pathophysiological conditions and normal synaptic activities. Among the ASIC subunits, ASIC2a and ASIC2b are alternative splicing products from the same gene, ACCN1. It has been shown that ASIC2 isoforms have differential subcellular distribution: ASIC2a targets the cell surface by itself, while ASIC2b resides in the ER. However, the underlying mechanism for this differential subcellular localization remained to be further elucidated. By constructing ASIC2 chimeras, we found that the first transmembrane (TM1) domain and the proximal post-TM1 domain (17 amino acids) of ASIC2a are critical for membrane targeting of the proteins. We also observed that replacement of corresponding residues in ASIC2b by those of ASIC2a conferred proton-sensitivity as well as surface expression to ASIC2b. We finally confirmed that ASIC2b is delivered to the cell surface from the ER by forming heteromers with ASIC2a, and that the N-terminal region of ASIC2a is additionally required for the ASIC2a-dependent membrane targeting of ASIC2b. Together, our study supports an important role of ASIC2a in membrane targeting of ASIC2b. PMID:27477936

  10. Project Description Advanced Fuel Cycle Initiative AFC-2A and AFC-2B Experiments

    SciTech Connect

    AFCI AFC-2A and AFC-2B Experiments Project Executi

    2007-03-01

    The proposed AFC-2A and AFC-2B irradiation experiments are a continuation of the AFC-1 fuel test series currently in progress in the ATR. This document discusses the experiments and the planned activities that will take place.

  11. 49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  12. 49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  13. 49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  14. 49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  15. 49 CFR Figure 2b to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2B Figure 2B to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  16. Ni(II) affects ubiquitination of core histones H2B and H2A

    SciTech Connect

    Karaczyn, Aldona A.; Golebiowski, Filip; Kasprzak, Kazimierz S. . E-mail: kasprkaz@mail.ncifcrf.gov

    2006-10-15

    The molecular mechanisms of nickel-induced malignant cell transformation include effects altering the structure and covalent modifications of core histones. Previously, we found that exposure of cells to Ni(II) resulted in truncation of histones H2A and H2B and thus elimination of some modification sites. Here, we investigated the effect of Ni(II) on one such modification, ubiquitination, of histones H2B and H2A in nuclei of cultured 1HAEo- and HPL1D human lung cells. After 1-5 days of exposure, Ni(II) up to 0.25 mM stimulated mono-ubiquitination of both histones, while at higher concentrations a suppression was found. Di-ubiquitination of H2A was not affected except for a drop after 5 days at 0.5 mM Ni(II). The decrease in mono-ubiquitination coincided with the appearance of truncated H2B that lacks the K120 ubiquitination site. However, prevention of truncation did not avert the decrease of H2B ubiquitination, indicating mechanistic independence of these effects. The changes in H2B ubiquitination did not fully coincide with concurrent changes in the nuclear levels of the ubiquitin-conjugating enzymes Rad6 and UbcH6. Overall, our results suggest that dysregulation of H2B ubiquitination is a part of Ni(II) adverse effects on gene expression and DNA repair which may assist in cell transformation.

  17. Localization of sulfonylurea receptor subunits, SUR2A and SUR2B, in rat heart.

    PubMed

    Zhou, Ming; He, Hui-Jing; Suzuki, Ryoji; Liu, Ke-Xiang; Tanaka, Osamu; Sekiguchi, Masaki; Itoh, Hideaki; Kawahara, Katsumasa; Abe, Hiroshi

    2007-08-01

    To understand the possible functions and subcellular localizations of sulfonylurea receptors (SURs) in cardiac muscle, polyclonal anti-SUR2A and anti-SUR2B antisera were raised. Immunoblots revealed both SUR2A and SUR2B expression in mitochondrial fractions of rat heart and other cellular fractions such as microsomes and cell membranes. Immunostaining detected ubiquitous expression of both SUR2A and SUR2B in rat heart in the atria, ventricles, interatrial and interventricular septa, and smooth muscles and endothelia of the coronary arteries. Electron microscopy revealed SUR2A immunoreactivity in the cell membrane, endoplasmic reticulum (ER), and mitochondria. SUR2B immunoreactivity was mainly localized in the mitochondria as well as in the ER and cell membrane. Thus, SUR2A and SUR2B are not only the regulatory subunits of sarcolemmal K(ATP) channels but may also function as regulatory subunits in mitochondrial K(ATP) channels and play important roles in cardioprotection. PMID:17438353

  18. Summary report on the fuel performance modeling of the AFC-2A, 2B irradiation experiments

    SciTech Connect

    Pavel G. Medvedev

    2013-09-01

    The primary objective of this work at the Idaho National Laboratory (INL) is to determine the fuel and cladding temperature history during irradiation of the AFC-2A, 2B transmutation metallic fuel alloy irradiation experiments containing transuranic and rare earth elements. Addition of the rare earth elements intends to simulate potential fission product carry-over from pyro-metallurgical reprocessing. Post irradiation examination of the AFC-2A, 2B rodlets revealed breaches in the rodlets and fuel melting which was attributed to the release of the fission gas into the helium gap between the rodlet cladding and the capsule which houses six individually encapsulated rodlets. This release is not anticipated during nominal operation of the AFC irradiation vehicle that features a double encapsulated design in which sodium bonded metallic fuel is separated from the ATR coolant by the cladding and the capsule walls. The modeling effort is focused on assessing effects of this unanticipated event on the fuel and cladding temperature with an objective to compare calculated results with the temperature limits of the fuel and the cladding.

  19. Structural evidence for Nap1-dependent H2A-H2B deposition and nucleosome assembly.

    PubMed

    Aguilar-Gurrieri, Carmen; Larabi, Amédé; Vinayachandran, Vinesh; Patel, Nisha A; Yen, Kuangyu; Reja, Rohit; Ebong, Ima-O; Schoehn, Guy; Robinson, Carol V; Pugh, B Franklin; Panne, Daniel

    2016-07-01

    Nap1 is a histone chaperone involved in the nuclear import of H2A-H2B and nucleosome assembly. Here, we report the crystal structure of Nap1 bound to H2A-H2B together with in vitro and in vivo functional studies that elucidate the principles underlying Nap1-mediated H2A-H2B chaperoning and nucleosome assembly. A Nap1 dimer provides an acidic binding surface and asymmetrically engages a single H2A-H2B heterodimer. Oligomerization of the Nap1-H2A-H2B complex results in burial of surfaces required for deposition of H2A-H2B into nucleosomes. Chromatin immunoprecipitation-exonuclease (ChIP-exo) analysis shows that Nap1 is required for H2A-H2B deposition across the genome. Mutants that interfere with Nap1 oligomerization exhibit severe nucleosome assembly defects showing that oligomerization is essential for the chaperone function. These findings establish the molecular basis for Nap1-mediated H2A-H2B deposition and nucleosome assembly. PMID:27225933

  20. Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

    PubMed

    Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

    2014-09-22

    Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. PMID:25148778

  1. Conical intersections between X2A1 and A2B2 electronic states of NO

    NASA Astrophysics Data System (ADS)

    Sardar, Subhankar; Mukherjee, Saikat; Paul, Amit Kumar; Adhikari, Satrajit

    2013-04-01

    We explore both the general symmetry-allowed accidental (SAA) conical intersections (CIs) and Renner-Teller (RT) interactions prevailed between the ground (X2A1) and first excited (A2B2) electronic states of NO in the configuration space of normal mode coordinates. Global ab initio potential-energy surfaces and Non Adiabatic Coupling Term (NACT) between those states are reported. For each of the three pairs of normal mode (Q1,Q2,Q3), calculated NACT show singularity at different positions, which are used to calculate Adiabatic-to-Diabatic Transformation (ADT) angles and thereby, the diagonal elements of ADT matrix display (i) sign change for odd number of SAA CI (s) and (ii) no sign change for even number of SAA CIs as well as Renner-Teller interactions. Similar to Jahn-Teller CI, the existence of SAA CIs are, further, confirmed by Longuet-Higgins' phase change.

  2. Impaired hippocampal synaptic plasticity and NR2A/2B expression ratio in remifentanil withdrawal rats.

    PubMed

    Wang, Yi-Yi; Liu, Shichang; Zhang, Nan; Yang, Jing; Zhang, Yinguo

    2016-03-01

    Remifentanil is a kind of synthetic opioid which has gained wide clinical acceptance by anesthesiologists. In this study, we attempted to test whether withdrawal effects on learning mechanisms can be triggered by repeated low-dose remifentanil treatment. Male Sprague-Dawley (SD) rats were subjected to remifentanil (50μg/kgs.c.) twice per day at 12h intervals for 15 days. When the animals of remifentanil group were withdrawn from remifentanil at 10h after the last injection, changes in open field test, Morris water maze test (MWM) and synaptic efficacy were examined in each group. We demonstrated that repeated exposure to 50μg/kg remifentanil produced enhanced locomotor activity indicating that a remifentanil addiction animal model in rats was established. MWM results showed that exposure to remifentanil had no influence on the spatial cognition. After withdrawal of remifentanil rats showed impaired spatial cognition. In electrophysiology test, remifentanil group rats showed a trend for a rightward shift of input/output relationship and significant deficits in maintenance of STP and LTP. Immunohistochemistry results demonstrated increased NR2A/NR2B ratio that should be included depression of LTP. In the whole-cell patch-clamp recording, after elimination from remifentanil incubation, mEPSC frequency was down regulated in hippocampal CA1 neurons, indicating that basal synaptic transmission were affected by remifentanil withdrawal. Taken together, the current findings demonstrate that the remifentanil withdrawn rats exhibit obvious impairment of hippocampus-dependent memory and synaptic plasticity. Increased hippocampal NR2A/NR2B expression ratio and the changes of basal synaptic transmission may participate in the impairment of LTP. PMID:26777139

  3. Neutron scattering studies of the H2a-H2b and (H3-H4)/sub 2/ histone complexes

    SciTech Connect

    Carlson, R.D.

    1982-01-01

    Neutron scattering experiments have shown that both the (H3-H4)/sub 2/ and H2a-H2b histone complexes are quite asymmetric in solution. The (H3-H4)/sub 2/ tetramer is an oblate or flattened structure, with a radius of gyration almost as large as that of the core octamer. If the tetramer is primarily globular, it must have an axial ratio of about 1:5. It is more likely, however, that this asymmetry results in part from N-terminal arms that extend outward approximately within the major plane of the particle. If this is the case, less asymmetric models for the globular part of the tetramer, including a dislocated disk, can be made consistent with the scattering data. The H2a-H2b dimer, on the other hand, is an elongated structure. 48 references, 12 figures, 1 table.

  4. 3D-pharmacophore models for selective A2A and A2B adenosine receptor antagonists.

    PubMed

    Wei, Jing; Wang, Songqing; Gao, Shaofen; Dai, Xuedong; Gao, Qingzhi

    2007-01-01

    Three-dimensional pharmacophore models were generated for A2A and A2B adenosine receptors (ARs) based on highly selective A2A and A2B antagonists using the Catalyst program. The best pharmacophore model for selective A2A antagonists (Hypo-A2A) was obtained through a careful validation process. Four features contained in Hypo-A2A (one ring aromatic feature (R), one positively ionizable feature (P), one hydrogen bond acceptor lipid feature (L), and one hydrophobic feature (H)) seem to be essential for antagonists in terms of binding activity and A2A AR selectivity. The best pharmacophore model for selective A2B antagonists (Hypo-A2B) was elaborated by modifying the Catalyst common features (HipHop) hypotheses generated from the selective A2B antagonists training set. Hypo-A2B also consists of four features: one ring aromatic feature (R), one hydrophobic aliphatic feature (Z), and two hydrogen bond acceptor lipid features (L). All features play an important role in A2B AR binding affinity and are essential for A2B selectivity. Both A2A and A2B pharmacophore models have been validated toward a wide set of test molecules containing structurally diverse selective antagonists of all AR subtypes. They are capable of identifying correspondingly high potent antagonists and differentiating antagonists between subtypes. The results of our study will act as a valuable tool for retrieving structurally diverse compounds with desired biological activities and designing novel selective adenosine receptor ligands. PMID:17330954

  5. Capsid proteins from PCV2a genotype confer greater protection against a PCV2b strain than those from PCV2b genotype in pigs: evidence for PCV2b strains becoming more predominant than PCV2a strains from 2000 to 2010s.

    PubMed

    Huang, Liping; Wang, Yiping; Wei, Yanwu; Chen, Dongjie; Liu, Dan; Du, Wenjuan; Xia, Deli; Wu, Hongli; Feng, Li; Liu, Changming

    2016-07-01

    Two major porcine circovirus type 2 (PCV2) genotypes, PCV2a and PCV2b, are recognized. PCV2a was predominant in the global pig population until 2000 while PCV2b became predominant from 2003 onward. The aim of this study was to analyze the immune protection conferred by two PCV2a and two PCV2b capsid proteins (Caps) in pigs challenged with a mutant PCV2b/YJ (mPCV2b/YJ) strain. Pigs vaccinated with PCV2a/LG-Cap and PCV2a/CL-Cap elicited significantly higher levels of PCV2-specific antibodies and neutralizing antibodies compared with PCV2b/JF-Cap and mPCV2b/YJ-Cap. Following a mPCV2b/YJ challenge, no viremia was detected in the PCV2a/LG-Cap and PCV2a/CL-Cap groups, while viremias were found in 20 and 40 % of the pigs in the PCV2b/JF-Cap and mPCV2b/YJ-Cap groups, respectively. Viral loads in the inguinal lymph nodes of pigs from the PCV2b/JF-Cap and mPCV2b/YJ-Cap groups were significantly higher than those in the PCV2a/LG-Cap and PCV2a/CL-Cap groups, but significantly lower than those of the challenge control group. Furthermore, PCV2 antigens were not detected in the inguinal lymph nodes of pigs from commercial vaccine groups, as well as the PCV2a/LG-Cap and PCV2a/CL-Cap groups, but were found in the challenge control (100 %, 5/5), PCV2b/JF-Cap (20 %, 1/5), and mPCV2b/YJ-Cap (20 %, 1/5) groups. These findings suggest that mPCV2b/YJ-Cap and PCV2b/JF-Cap were less immunogenic than PCV2a/LG-Cap and PCV2a/CL-Cap. We speculate that a genotypic shift from PCV2a to PCV2b might be the result of the majority of PCV2a strains being more immunogenic than the majority of PCV2b strains. These results provide a possible explanation for why PCV2b strains are more likely to cause epidemics than PCV2a strains. It tells us that PCV2 pathogenesis may be associated with its immunogenicity to some extent. PMID:27020283

  6. Acute hypoxia differentially affects the NMDA receptor NR1, NR2A and NR2B subunit mRNA levels in the developing chick optic tectum: stage-dependent plasticity in the 2B-2A ratio.

    PubMed

    Vacotto, Marina; Rapacioli, Melina; Flores, Vladimir; de Plazas, Sara Fiszer

    2010-10-01

    It is known that the NMDA-R NR1 subunit is needed for the receptor activity and that under hypoxia the evolution toward apoptosis or neuronal survival depends on the balance NR2A/NR2B subunits. This paper analyzes the effect of acute hypoxia on the above mentioned subunits mRNAs during development. The mean percentage of NR1+ neurons displayed the higher plasticity during development while the NR2A+ neurons the higher stability. Acute hypoxia increased the mean percentage of NR1+ and NR2B+ neurons at ED12 but only that of NR1+ neurons at ED18. Acute hypoxia increased the levels of expression of NR1 and NR2B mRNAs at ED12 without changes in the NR2A mRNA. During early stages there is a higher sensitivity to change the subunits mRNA levels under a hypoxic treatment. At ED12 acute hypoxia increased the probability of co-expression of the NR1-NR2A and NR1-NR2B subunits combinations, the level of NR1 and NR2B and the ratio NR2B/NR2A. These conditions facilitate the evolution towards apoptosis. PMID:20596770

  7. Identification of natural recombinants derived from PCV2a and PCV2b.

    PubMed

    Hu, J; Zhai, S L; Zeng, S Y; Sun, B B; Deng, S F; Chen, H L; Zheng, Y; Wang, H X; Li, X P; Liu, J K; Cheng, S; Zhou, X; Zhai, J Q; Luo, M L

    2015-01-01

    Porcine circovirus type 2 (PCV2) is considered to be the main pathogen in PC-associated diseases, and significantly affects the global pig-producing industry. PCV2 continuously evolves by point mutations and genome recombinations. In the present study, we aimed to further identify recombinant PCV2 strains. We used polymerase chain reaction to detect PCV2 in the carcasses of pigs with suspected infections from different regions of Guangdong Province in China. DNA was extracted from samples with confirmed infection and full- genome amplification, sequencing, phylogenetic tree construction, gene recombination detection, and sequence alignment were performed in gene recombination analysis. Our results show that recombination occurred between the strains SHC (DQ104421) and ZhuJi2003 (AY579893). The recombination resulted in three recombinants: GD003 (KM503044), GD005 (KM487708), and GD008 (KM487709). Further analyses revealed that these novel recombinants appeared to result from recombination between the PCV2a and PCV2b strains, with crossover regions located in ORF2. This study was a comprehensive analysis that used several different methods, which demonstrated that a cluster of PCV2 strains resulted from the same type of inter-genotypic recombination pattern, with a breakpoint in the structural protein coding region. The results of our study provide both information on the recombination mechanism and disease pathogenesis and useful data for the prevention of PCV2 in the swine industry. PMID:26436503

  8. The real factor for polypeptide elongation in Dictyostelium cells is EF-2B, not EF-2A

    SciTech Connect

    Yoshino, Tomoko; Maeda, Yasuo; Amagai, Aiko . E-mail: aiamagai@mail.tains.tohoku.ac.jp

    2007-08-03

    Polypeptide elongation factor 2 (EF-2) plays an essential role in protein synthesis and is believed to be indispensable for cell proliferation. Recently, it has been demonstrated that there are two kinds of EF-2 (EF-2A and EF-2B with 76.6% of sequence identity at the amino acid level) in Dictyostelium discoideum. Although the knockout of EF-2A slightly impaired cytokinesis, EF-2A null cells exhibited almost normal protein synthesis and cell growth, suggesting that there is another molecule capable of compensating for EF-2 function. Since EF-2B is the most likely candidate, we examined its function using ef-2b knockdown cells prepared by the RNAi method. Our results strongly suggest that EF-2B is required for protein synthesis and cell proliferation, functioning as the real EF-2. Interestingly, the expressions of ef-2a and ef-2b mRNAs during development are reversely regulated, and the ef-2b expression is greatly augmented in ef-2a null cells.

  9. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase.

    PubMed

    Guenebeaud, Céline; Goldschneider, David; Castets, Marie; Guix, Catherine; Chazot, Guillaume; Delloye-Bourgeois, Céline; Eisenberg-Lerner, Avital; Shohat, Galit; Zhang, Mingjie; Laudet, Vincent; Kimchi, Adi; Bernet, Agnès; Mehlen, Patrick

    2010-12-22

    The UNC5H dependence receptors promote apoptosis in the absence of their ligand, netrin-1, and this is important for neuronal and vascular development and for limitation of cancer progression. UNC5H2 (also called UNC5B) triggers cell death through the activation of the serine-threonine protein kinase DAPk. While performing a siRNA screen to identify genes implicated in UNC5H-induced apoptosis, we identified the structural subunit PR65β of the holoenzyme protein phosphatase 2A (PP2A). We show that UNC5H2/B recruits a protein complex that includes PR65β and DAPk and retains PP2A activity. PP2A activity is required for UNC5H2/B-induced apoptosis, since it activates DAPk by triggering its dephosphorylation. Moreover, netrin-1 binding to UNC5H2/B prevents this effect through interaction of the PP2A inhibitor CIP2A to UNC5H2/B. Thus we show here that, in the absence of netrin-1, recruitment of PP2A to UNC5H2/B allows the activation of DAPk via a PP2A-mediated dephosphorylation and that this mechanism is involved in angiogenesis regulation. PMID:21172653

  10. Co-activation of NR2A and NR2B subunits induces resistance to fear extinction.

    PubMed

    Leaderbrand, Katherine; Corcoran, Kevin A; Radulovic, Jelena

    2014-09-01

    Unpredictable stress is known to profoundly enhance susceptibility to fear and anxiety while reducing the ability to extinguish fear when threat is no longer present. Accordingly, partial aversive reinforcement, via random exposure to footshocks, induces fear that is resistant to extinction. Here we sought to determine the hippocampal mechanisms underlying susceptibility versus resistance to context fear extinction as a result of continuous (CR) and partial (PR) reinforcement, respectively. We focused on N-methyl-D-aspartate receptor (NMDAR) subunits 2A and B (NR2A and NR2B) as well as their downstream signaling effector, extracellular signal-regulated kinase (ERK), based on their critical role in the acquisition and extinction of fear. Pharmacological inactivation of NR2A, but not NR2B, blocked extinction after CR, whereas inactivation of NR2A, NR2B, or both subunits facilitated extinction after PR. The latter finding suggests that co-activation of NR2A and NR2B contributes to persistent fear following PR. In contrast to CR, PR increased membrane levels of ERK and NR2 subunits after the conditioning and extinction sessions, respectively. In parallel, nuclear activation of ERK was significantly reduced after the extinction session. Thus, co-activation and increased surface expression of NR2A and NR2B, possibly mediated by ERK, may cause persistent fear. These findings suggest that patients with post-traumatic stress disorder (PTSD) may benefit from antagonism of specific NR2 subunits. PMID:24055686

  11. Pharmacogenetics of CYP2B6, CYP2A6 and UGT2B7 in HIV treatment in African populations: focus on efavirenz and nevirapine.

    PubMed

    Čolić, Antoinette; Alessandrini, Marco; Pepper, Michael S

    2015-05-01

    The CYP450 and UGT enzymes are involved in phase I and phase II metabolism of the majority of clinically prescribed drugs, including the non-nucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, used in the treatment of HIV/AIDS. Variations in the activity of these enzymes due to gene polymorphisms can affect an individual's drug response or may lead to adverse drug reactions. There is an inter-ethnic distribution in the frequency of these polymorphisms, with African populations exhibiting higher genetic diversity compared to other populations. African specific alleles with clinical relevance have also emerged. Given the high prevalence of HIV/AIDS in sub-Saharan Africa, understanding the frequency of pharmacogenetically relevant alleles in populations of African origin, and their impact on efavirenz and nevirapine metabolism, is becoming increasingly critical. This review aims to investigate ethnic variation of CYP2B6, CYP2A6 and UGT2B7, and to understand the pharmacogenetic relevance when comparing frequencies in African populations to other populations worldwide. PMID:25391641

  12. Two Histone Variants TH2A and TH2B Enhance Human Induced Pluripotent Stem Cell Generation.

    PubMed

    Huynh, Linh My; Shinagawa, Toshie; Ishii, Shunsuke

    2016-02-01

    There are two major methods of reprogramming: generation of induced pluripotent stem cells (iPSCs) by overexpressing embryonic stem cell-specific transcription factors (OCT4, SOX2, KLF4, and c-MYC) and somatic cell nuclear transfer by oocyte-specific factors. Previously, we reported oocyte-enriched histone variants TH2A, TH2B, and the histone chaperone nucleoplasmin (NPM2) enhance the reprogramming by OSKM in mice by inducing open chromatin structure. In this study, we showed that human TH2A, TH2B, and NPM2 enhance the OSKM-induced reprogramming of adult and neonatal human dermal fibroblasts and umbilical vein endothelial cells. Pluripotency of iPSCs generated by coexpressing OSKM, TH2A, TH2B, and NPM2 was shown by in vitro and in vivo differentiation assays. These iPSCs gave rise to highly differentiated teratomas compared to iPSCs induced by OSKM alone. Genome-wide analysis suggests a possibility that TH2A, TH2B, and NPM2 might regulate genes that are involved in naïve stem cell stage. Thus, TH2A, TH2B, and NPM2 enhance reprogramming of human somatic cells and improve the quality of human iPSCs. PMID:26649967

  13. Serotonin 2A and 2B receptor-induced phrenic motor facilitation: differential requirement for spinal NADPH oxidase activity

    PubMed Central

    MacFarlane, P.M.; Vinit, S.; Mitchell, G.S.

    2011-01-01

    Acute intermittent hypoxia (AIH) facilitates phrenic motor output by a mechanism that requires spinal serotonin (type 2) receptor activation, NADPH oxidase activity and formation of reactive oxygen species (ROS). Episodic spinal serotonin (5-HT) receptor activation alone, without changes in oxygenation, is sufficient to elicit NADPH oxidase-dependent phrenic motor facilitation (pMF). Here we investigated: 1) whether serotonin 2A and/or 2B (5-HT2a/b) receptors are expressed in identified phrenic motor neurons, and 2) which receptor subtype is capable of eliciting NADPH-oxidase-dependent pMF. In anesthetized, artificially ventilated adult rats, episodic C4 intrathecal injections (3 × 6µl injections, 5 min intervals) of a 5-HT2a (DOI) or 5-HT2b (BW723C86) receptor agonist elicited progressive and sustained increases in integrated phrenic nerve burst amplitude (i.e. pMF), an effect lasting at least 90 minutes post-injection for both receptor subtypes. 5-HT2a and 5-HT2b receptor agonist-induced pMF were both blocked by selective antagonists (ketanserin and SB206553, respectively), but not by antagonists to the other receptor subtype. Single injections of either agonist failed to elicit pMF, demonstrating a need for episodic receptor activation. Phrenic motor neurons retrogradely labeled with cholera toxin B fragment expressed both 5-HT2a and 5-HT2b receptors. Pre-treatment with NADPH oxidase inhibitors (apocynin and DPI) blocked 5-HT2b, but not 5-HT2a-induced pMF. Thus, multiple spinal type 2 serotonin receptors elicit pMF, but they act via distinct mechanisms that differ in their requirement for NADPH oxidase activity. PMID:21223996

  14. Singular PCV2a or PCV2b infection results in apoptosis of hepatocytes in clinically affected gnotobiotic pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine circovirus type 2 (PCV2) which can be further subdivide into two main genotypes, PCV2a and PCV2b, is often clinically associated with respiratory signs, failure-to-thrive, and diarrhea. The precise pathogenesis of PCV2, and in particular its involvement in apoptosis, is controversial. The ob...

  15. Singular PCV2a or PCV2b Infection Results in Apoptosis of Hepatocytes in Clinically Affected Gnotobiotic Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Systemic infection with porcine circovirus type 2 (PCV2) is often clinically associated with respiratory signs, failure to thrive and diarrhea [1]. Currently, PCV2 can be further subdivided into two main genotypes, PCV2a and PCV2b which under experimental conditions result in very simi...

  16. Characterization of rainbow trout myostatin-2 genes (rtMSTN-2a & -2b): genomic organization, differential expression and pseudogenization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Myostatin is an extremely potent negative regulator of vertebrate skeletal muscle development. A phylogenetic analysis suggests that salmonids should possess four distinct genes, although only MSTN-1 orthologs have been characterized. Described herein are the rainbow trout (rt) MSTN-2a and -2b genes...

  17. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B

    PubMed Central

    2015-01-01

    Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology. PMID:25799074

  18. Mapping Post-translational Modifications of Histones H2A, H2B and H4 in Schizosaccharomyces pombe.

    PubMed

    Xiong, Lei; Wang, Yinsheng

    2011-03-30

    Core histones are known to carry a variety of post-translational modifications (PTMs), including acetylation, phosphorylation, methylation and ubiquitination, which play important roles in the epigenetic control of gene expression. The nature and biological functions of these PTMs in histones from plants, animals and budding yeast have been extensively investigated. In contrast, the corresponding studies for fission yeast were mainly focused on histone H3. In the present study, we applied LC-nano-ESI-MS/MS, coupled with multiple protease digestion, to identify PTMs in histones H2A, H2B and H4 from Schizosaccharomyces pombe (S. pombe), the typical model organism of fission yeast. Various protease digestions provided high sequence coverage for PTM mapping, and accurate mass measurement of fragment ions allowed for unambiguous differentiation of acetylation from tri-methylation. Many modification sites conserved in other organisms were identified in S. pombe. In addition, some unique modification sites, including N-terminal acetylation in H2A and H2B as well as K123 acetylation in H2A.β, were observed. Our results provide a comprehensive picture of the PTMs of histones H2A, H2B and H4 in S. pombe, which serves as a foundation for future investigations on the regulation and functions of histone modifications in this important model organism. PMID:21516229

  19. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B.

    PubMed

    Chen, Peiling; Chaikuad, Apirat; Bamborough, Paul; Bantscheff, Marcus; Bountra, Chas; Chung, Chun-Wa; Fedorov, Oleg; Grandi, Paola; Jung, David; Lesniak, Robert; Lindon, Matthew; Müller, Susanne; Philpott, Martin; Prinjha, Rab; Rogers, Catherine; Selenski, Carolyn; Tallant, Cynthia; Werner, Thilo; Willson, Timothy M; Knapp, Stefan; Drewry, David H

    2016-02-25

    Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology. PMID:25799074

  20. Association of concurrent porcine circovirus (PCV) 2a and 2b infection with PCV associated disease in vaccinated pigs.

    PubMed

    Gerber, Priscilla F; Johnson, John; Shen, Huigang; Striegel, Dave; Xiao, Chao-Ting; Halbur, Patrick G; Opriessnig, Tanja

    2013-10-01

    Investigations were performed to characterize porcine circovirus (PCV) 2 infection in 10 week old pigs from a case of apparent vaccine failure. Thirty serum samples were collected from affected or non-affected pigs and tested for anti-PCV2 antibodies and PCV2 DNA. To address potential PCV2 vaccine compliance issues, samples were tested for antibodies against baculovirus and Mycoplasma hyopneumoniae antigens present in the PCV2 vaccine utilized in this herd. Both PCV2a and PCV2b DNA were detected in 76.6% (90% positive for PCV2a, 86.6% positive for PCV2b), anti-PCV2 IgG in 90%, anti-baculovirus IgG in 50%, and anti-M. hyopneumoniae IgG in 43.3% of the samples. Frequency of baculovirus and M. hyopneumoniae seropositive pigs was significantly lower in affected pigs. The finding that only 50% of the pigs developed a detectable immune response to vaccination suggests poor vaccine compliance or efficacy. Concurrent PCV2a and PCV2b infection was common and may have resulted in enhanced PCV2 replication. PMID:23829995

  1. Generation and Characterization of a CYP2A13/2B6/2F1-Transgenic Mouse Model

    PubMed Central

    Wei, Yuan; Wu, Hong; Li, Lei; Liu, Zhihua; Zhou, Xin; Zhang, Qing-Yu; Weng, Yan; D'Agostino, Jaime; Ling, Guoyu; Zhang, Xiuling; Kluetzman, Kerri; Yao, Yunyi

    2012-01-01

    CYP2A13, CYP2B6, and CYP2F1, which are encoded by neighboring cytochrome P450 genes on human chromosome 19, are active in the metabolic activation of many drugs, respiratory toxicants, and chemical carcinogens. To facilitate studies on the regulation and function of these human genes, we have generated a CYP2A13/2B6/2F1-transgenic (TG) mouse model (all *1 alleles). Homozygous transgenic mice are normal with respect to gross morphological features, development, and fertility. The tissue distribution of transgenic mRNA expression agreed well with the known respiratory tract-selective expression of CYP2A13 and CYP2F1 and hepatic expression of CYP2B6 in humans. CYP2A13 protein was detected through immunoblot analyses in the nasal mucosa (NM) (∼100 pmol/mg of microsomal protein; similar to the level of mouse CYP2A5) and the lung (∼0.2 pmol/mg of microsomal protein) but not in the liver of the TG mice. CYP2F1 protein, which could not be separated from mouse CYP2F2 in immunoblot analyses, was readily detected in the NM and lung but not the liver of TG/Cyp2f2-null mice, at levels 10- and 40-fold, respectively, lower than that of mouse CYP2F2 in the TG mice. CYP2B6 protein was detected in the liver (∼0.2 pmol/mg of microsomal protein) but not the NM or lung (with a detection limit of 0.04 pmol/mg of microsomal protein) of the TG mice. At least one transgenic protein (CYP2A13) seems to be active, because the NM of the TG mice had greater in vitro and in vivo activities in bioactivation of a CYP2A13 substrate, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (a lung carcinogen), than did the NM of wild-type mice. PMID:22397853

  2. Targeted mutagenesis of aryl hydrocarbon receptor 2a and 2b genes in Atlantic killifish (Fundulus heteroclitus).

    PubMed

    Aluru, Neelakanteswar; Karchner, Sibel I; Franks, Diana G; Nacci, Diane; Champlin, Denise; Hahn, Mark E

    2015-01-01

    Understanding molecular mechanisms of toxicity is facilitated by experimental manipulations, such as disruption of function by gene targeting, that are especially challenging in non-standard model species with limited genomic resources. While loss-of-function approaches have included gene knock-down using morpholino-modified oligonucleotides and random mutagenesis using mutagens or retroviruses, more recent approaches include targeted mutagenesis using zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology. These latter methods provide more accessible opportunities to explore gene function in non-traditional model species. To facilitate evaluation of toxic mechanisms for important categories of aryl hydrocarbon pollutants, whose actions are known to be receptor mediated, we used ZFN and CRISPR-Cas9 approaches to generate aryl hydrocarbon receptor 2a (AHR2a) and AHR2b gene mutations in Atlantic killifish (Fundulus heteroclitus) embryos. This killifish is a particularly valuable non-traditional model, with multiple paralogs of AHR whose functions are not well characterized. In addition, some populations of this species have evolved resistance to toxicants such as halogenated aromatic hydrocarbons. AHR-null killifish will be valuable for characterizing the role of the individual AHR paralogs in evolved resistance, as well as in normal development. We first used five-finger ZFNs targeting exons 1 and 3 of AHR2a. Subsequently, CRISPR-Cas9 guide RNAs were designed to target regions in exon 2 and 3 of AHR2a and AHR2b. We successfully induced frameshift mutations in AHR2a exon 3 with ZFN and CRISPR-Cas9 guide RNAs, with mutation frequencies of 10% and 16%, respectively. In AHR2b, mutations were induced using CRISPR-Cas9 guide RNAs targeting sites in both exon 2 (17%) and exon 3 (63%). We screened AHR2b exon 2 CRISPR-Cas9-injected embryos for off

  3. Targeted mutagenesis of aryl hydrocarbon receptor 2a and 2b genes in Atlantic killifish (Fundulus heteroclitus)

    PubMed Central

    Aluru, Neelakanteswar; Karchner, Sibel I.; Franks, Diana G.; Nacci, Diane; Champlin, Denise; Hahn, Mark E.

    2014-01-01

    Understanding molecular mechanisms of toxicity is facilitated by experimental manipulations, such as disruption of function by gene targeting, that are especially challenging in non-standard model species with limited genomic resources. While loss-of-function approaches have included gene knock-down using morpholino-modified oligonucleotides and random mutagenesis using mutagens or retroviruses, more recent approaches include targeted mutagenesis using zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 technology. These latter methods provide more accessible opportunities to explore gene function in non-traditional model species. To facilitate evaluations of toxic mechanisms for important categories of aryl hydrocarbon pollutants, whose actions are known to be receptor mediated, we used ZFN and CRISPR-Cas9 approaches to generate aryl hydrocarbon receptor 2a (AHR2a) and AHR2b gene mutations in Atlantic killifish (Fundulus heteroclitus) embryos. This killifish is a particularly valuble non-traditional model for this study, with multiple paralogs of AHR whose functions are not well characterized. In addition, some populations of this species have evolved resistance to toxicants such as halogenated aromatic hydrocarbons. AHR-null killifish will be valuable for characterizing the role of the individual AHR paralogs in evolved resistance, as well as in normal development. We first used five-finger ZFNs targeting exons 1 and 3 of AHR2a. Subsequently, CRISPR-Cas9 guide RNAs were designed to target regions in exon 2 and 3 of AHR2a and AHR2b. We successfully induced frameshift mutations in AHR2a exon 3 with ZFN and CRISPR-Cas9 guide RNAs, with mutation frequencies of 10% and 16%, respectively. In AHR2b, mutations were induced using CRISPR-Cas9 guide RNAs targeting sites in both exon 2 (17%) and exon 3 (63%). We screened AHR2b exon 2 CRISPR-Cas9-injected embryos for

  4. The MATROSHKA experiment: results and comparison from extravehicular activity (MTR-1) and intravehicular activity (MTR-2A/2B) exposure.

    PubMed

    Berger, Thomas; Bilski, Paweł; Hajek, Michael; Puchalska, Monika; Reitz, Günther

    2013-12-01

    Astronauts working and living in space are exposed to considerably higher doses and different qualities of ionizing radiation than people on Earth. The multilateral MATROSHKA (MTR) experiment, coordinated by the German Aerospace Center, represents the most comprehensive effort to date in radiation protection dosimetry in space using an anthropomorphic upper-torso phantom used for radiotherapy treatment planning. The anthropomorphic upper-torso phantom maps the radiation distribution as a simulated human body installed outside (MTR-1) and inside different compartments (MTR-2A: Pirs; MTR-2B: Zvezda) of the Russian Segment of the International Space Station. Thermoluminescence dosimeters arranged in a 2.54 cm orthogonal grid, at the site of vital organs and on the surface of the phantom allow for visualization of the absorbed dose distribution with superior spatial resolution. These results should help improve the estimation of radiation risks for long-term human space exploration and support benchmarking of radiation transport codes. PMID:24252101

  5. Simvastatin enhances NMDA receptor GluN2B expression and phosphorylation of GluN2B and GluN2A through increased histone acetylation and Src signaling in hippocampal CA1 neurons.

    PubMed

    Chen, Tingting; Zhang, Baofeng; Li, Guoxi; Chen, Lei; Chen, Ling

    2016-08-01

    Simvastatin (SV) can improve cognitive deficits in Alzheimer's disease patients and mice. Herein, we report that the administration of SV (20 mg/kg) for 5 days in mice (SV-mice) or the treatment of slices with SV (10 μM) for 4 h (SV-slices) could increase the density of NMDA-evoked inward currents (INMDA) in hippocampal CA1 pyramidal cells, which were blocked by farnesol (FOH) that converts farnesyl pyrophosphate (FPP), but not geranylgeraniol (GGOH) that increases geranylgeranylpyrophosphate (GGPP). Sensitivity of INMDA to ifenprodil in SV-mice or SV-slices was significantly increased. The levels of hippocampal GluN2B and GluN2A or Src phosphorylation in SV-mice or SV-slices were higher than controls, which were sensitive to FOH. The Src inhibitor PP2 could inhibit the SV-enhanced phosphorylation of GluN2B and GluN2A and SV-augmented INMDA, but PI3K inhibitor LY294002 did not. The levels of GluN2B mRNA and protein were elevated in SV-mice, which was abolished by FOH, but not by GGOH or PP2. Furthermore, the histone H3K9 and H3K27 acetylation of GluN2B promoter was increased in SV-mice, which was suppressed by FOH rather than GGOH or PP2. In control mice and slices, the reduction of FPP by farnesyl transferase inhibitor could increase the levels of GluN2B expression, the histone H3K9 and H3K27 acetylation and enhance the phosphorylation of GluN2B, GluN2A and Src. The findings indicate that the administration of SV can enhance GluN2B expression and GluN2B and GluN2A phosphorylation leading to augmentation of NMDAR activity through reducing FPP to increase histone acetylation of GluN2B and Src signaling. PMID:27016018

  6. 76 FR 46597 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2A12 (CL-601) and CL-600-2B16 (CL-601-3A...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    .... Model CL-600-2A12 (CL- 601) and CL-600-2B16 (CL-601-3A, CL-601-3R, and CL-604 Variants) Airplanes... Bombardier, Inc. model-- Task(s)-- Initial compliance time (whichever occurs later)-- CL-600-2A12 (CL-601... icing. accumulation of 4,800 after the effective inclusive; and CL-600-2B16 (CL- total flight hours;...

  7. Efficacy and Tolerability of Peginterferon α-2a and Peginterferon α-2b, Both plus Ribavirin, for Chronic Hepatitis C: A Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Zhuang, Liping; Yang, Lei; Chen, Xiaorong

    2013-01-01

    Background. The efficacy and tolerability of peginterferon α-2a and peginterferon α-2b in chronic hepatitis C (CHC) patients remain controversial. Methods. PubMed, Ovid, and Cochrane libraries were electronically searched until August 30, 2012. Studies that met the inclusion criteria were systematically evaluated by two reviewers independently. Results. The overall sustained virologic response (SVR) rate of the peginterferon α-2a group was significantly higher than that of the peginterferon α-2b group (46.7% versus 42.4%, P value = 0.01). The same tendency was observed for naïve, genotype 1/4, and genotype 2/3 patients. The early virologic response (EVR) and end-of-treatment response (ETR) rates were significantly higher in the peginterferon α-2a group than in the peginterferon α-2b group (56.1% versus 49.8%, P < 0.0001; 67.9% versus 56.6%, P < 0.00001, resp.). Peginterferon α-2a had a significantly lower discontinuation rate than peginterferon α-2b (27.9% versus 33.9%, P < 0.0001) in naïve patients. In both naïve CHC and hepatitis C virus genotype 1 patients, peginterferon α-2a had a higher relapse rate than peginterferon α-2b. Conclusions. Peginterferon α-2a has superior efficacy with higher EVR, ETR, and SVR than peginterferon α-2b for CHC patients, both plus ribavirin. Peginterferon α-2a might obtain a similar or even lower discontinuation rate than peginterferon α-2b. However, peginterferon α-2a had a higher relapse rate than peginterferon α-2b. PMID:23662098

  8. PHOX2A and PHOX2B are differentially regulated during retinoic acid-driven differentiation of SK-N-BE(2)C neuroblastoma cell line

    PubMed Central

    Di Lascio, Simona; Saba, Elena; Belperio, Debora; Raimondi, Andrea; Lucchetti, Helen; Fornasari, Diego; Benfante, Roberta

    2016-01-01

    PHOX2B and its paralogue gene PHOX2A are two homeodomain proteins in the network regulating the development of autonomic ganglia that have been associated with the pathogenesis of neuroblastoma (NB), because of their over-expression in different NB cell lines and tumour samples. We used the SK-N-BE(2)C cell line to show that all-trans retinoic acid (ATRA), a drug that is widely used to inhibit growth and induce differentiation in NBs, regulates both PHOX2A and PHOX2B expression, albeit by means of different mechanisms: it up-regulates PHOX2A and down-regulates PHOX2B. Both mechanisms act at transcriptional level, but prolonged ATRA treatment selectively degrades the PHOX2A protein, whereas the corresponding mRNA remains up-regulated. Further, we show that PHOX2A is capable of modulating PHOX2B expression, but this mechanism is not involved in the PHOX2B down-regulation induced by retinoic acid. Our findings demonstrate that PHOX2A expression is finely controlled during retinoic acid differentiation and this, together with PHOX2B down-regulation, reinforces the idea that they may be useful biomarkers for NB staging, prognosis and treatment decision making. PMID:26902400

  9. Role of the C-terminal domains of rice (Oryza sativa L.) bZIP proteins RF2a and RF2b in regulating transcription

    PubMed Central

    Liu, Yi; Dai, Shunhong; Beachy, Roger N.

    2007-01-01

    Rice (Oryza sativa L.) transcription factors RF2a and RF2b are bZIP (basic leucine zipper) proteins that interact with, and activate transcription from the RTBV (rice tungro bacilliform virus) promoter. Here we characterize the C-terminal domains of RF2a and RF2b: these domains are rich in glutamine and proline/glutamine, respectively. Affinity pull-down assays demonstrated that the C-terminal domains of RF2a and RF2b can associate to form either homodimers or heterodimers; however, they do not interact with other domains of RF2a or RF2b. Results of in vitro transcription assays using a rice whole-cell extract demonstrate that the C-terminal domains of both RF2a and RF2b activate transcription from the RTBV promoter. In addition, dimerization of the RF2a C-terminal domain is involved in regulating the transcription activation function of RF2a. The predicted helical region within the RF2a C-terminal glutamine-rich domain was determined to be involved in inter-molecular dimerization, and contributed to the regulatory functions of RF2a in these assays. PMID:17371296

  10. Origin and evolution of GATA2a and GATA2b in teleosts: insights from tongue sole, Cynoglossus semilaevis.

    PubMed

    Liu, Jinxiang; Jiang, Jiajun; Wang, Zhongkai; He, Yan; Zhang, Quanqi

    2016-01-01

    Background. Following the two rounds of whole-genome duplication that occurred during deuterostome evolution, a third genome duplication occurred in the lineage of teleost fish and is considered to be responsible for much of the biological diversification within the lineage. GATA2, a member of GATA family of transcription factors, is an important regulator of gene expression in hematopoietic cell in mammals, yet the role of this gene or its putative paralogs in ray-finned fishes remains relatively unknown. Methods. In this study, we attempted to identify GATA2 sequences from the transcriptomes and genomes of multiple teleosts using the bioinformatic tools MrBayes, MEME, and PAML. Following identification, comparative analysis of genome structure, molecular evolution rate, and expression by real-time qPCR were used to predict functional divergence of GATA2 paralogs and their relative transcription in organs of female and male tongue soles (Cynoglossus semilaevis). Results. Two teleost GATA2 genes were identified in the transcriptomes of tongue sole and Japanese flounder (Paralichthysolivaceus). Synteny and phylogenetic analysis confirmed that the two genes likely originated from the teleost-specific genome duplication . Additionally, selection pressure analysis predicted these gene duplicates to have undergone purifying selection and possible divergent new functions. This was supported by differential expression pattern of GATA2a and GATA2b observed in organs of female and male tongue soles. Discussion. Our results indicate that two GATA2 genes originating from the first teleost-specific genome duplication have remained transcriptionally active in some fish species and have likely undergone neofunctionalization. This knowledge provides novel insights into the evolution of the teleost GATA2 genes and constituted important groundwork for further research on the GATA gene family. PMID:27019782

  11. Origin and evolution of GATA2a and GATA2b in teleosts: insights from tongue sole, Cynoglossus semilaevis

    PubMed Central

    Liu, Jinxiang; Jiang, Jiajun; Wang, Zhongkai; He, Yan

    2016-01-01

    Background. Following the two rounds of whole-genome duplication that occurred during deuterostome evolution, a third genome duplication occurred in the lineage of teleost fish and is considered to be responsible for much of the biological diversification within the lineage. GATA2, a member of GATA family of transcription factors, is an important regulator of gene expression in hematopoietic cell in mammals, yet the role of this gene or its putative paralogs in ray-finned fishes remains relatively unknown. Methods. In this study, we attempted to identify GATA2 sequences from the transcriptomes and genomes of multiple teleosts using the bioinformatic tools MrBayes, MEME, and PAML. Following identification, comparative analysis of genome structure, molecular evolution rate, and expression by real-time qPCR were used to predict functional divergence of GATA2 paralogs and their relative transcription in organs of female and male tongue soles (Cynoglossus semilaevis). Results. Two teleost GATA2 genes were identified in the transcriptomes of tongue sole and Japanese flounder (Paralichthysolivaceus). Synteny and phylogenetic analysis confirmed that the two genes likely originated from the teleost-specific genome duplication . Additionally, selection pressure analysis predicted these gene duplicates to have undergone purifying selection and possible divergent new functions. This was supported by differential expression pattern of GATA2a and GATA2b observed in organs of female and male tongue soles. Discussion. Our results indicate that two GATA2 genes originating from the first teleost-specific genome duplication have remained transcriptionally active in some fish species and have likely undergone neofunctionalization. This knowledge provides novel insights into the evolution of the teleost GATA2 genes and constituted important groundwork for further research on the GATA gene family. PMID:27019782

  12. Binding specificity of polypeptide substrates in NS2B/NS3pro serine protease of dengue virus type 2: A molecular dynamics Study.

    PubMed

    Yotmanee, Pathumwadee; Rungrotmongkol, Thanyada; Wichapong, Kanin; Choi, Sy Bing; Wahab, Habibah A; Kungwan, Nawee; Hannongbua, Supot

    2015-07-01

    The pathogenic dengue virus (DV) is a growing global threat, particularly in South East Asia, for which there is no specific treatment available. The virus possesses a two-component (NS2B/NS3) serine protease that cleaves the viral precursor proteins. Here, we performed molecular dynamics simulations of the NS2B/NS3 protease complexes with six peptide substrates (capsid, intNS3, 2A/2B, 4B/5, 3/4A and 2B/3 containing the proteolytic site between P(1) and P(1)' subsites) of DV type 2 to compare the specificity of the protein-substrate binding recognition. Although all substrates were in the active conformation for cleavage reaction by NS2B/NS3 protease, their binding strength was somewhat different. The simulated results of intermolecular hydrogen bonds and decomposition energies suggested that among the ten substrate residues (P(5)-P(5)') the P(1) and P(2) subsites play a major role in the binding with the focused protease. The arginine residue at these two subsites was found to be specific preferential binding at the active site with a stabilization energy of <-10 kcal mol(-1). Besides, the P(3), P(1)', P(2)' and P(4)' subsites showed a less contribution in binding interaction (<-2 kcal mol(-1)). The catalytic water was detected nearby the carbonyl oxygen of the P(1) reacting center of the capsid, intNS3, 2A/2B and 4B/5 peptides. These results led to the order of absolute binding free energy (ΔGbind) between these substrates and the NS2B/NS3 protease ranked as capsid>intNS3>2A/2B>4B/5>3/4A>2B/3 in a relative correspondence with previous experimentally derived values. PMID:26086900

  13. Nutrient status modulates the expression of nesfatin-1 encoding nucleobindin 2A and 2B mRNAs in zebrafish gut, liver and brain.

    PubMed

    Hatef, Azadeh; Shajan, Sooraj; Unniappan, Suraj

    2015-05-01

    Nesfatin-1 is a naturally occurring, 82-amino acid peptide processed from the precursor nucleobindin 2 (NUCB2), a highly conserved protein among vertebrates. In fish, two isoforms of NUCB2 (NUCB2A and NUCB2B) exist, and nesfatin-1 has been identified in goldfish and Ya fish. We recently reported the presence and appetite suppressing effects of nesfatin-1 in goldfish. The main objectives of this study were to characterize NUCB2 in zebrafish, and determine whether NUCB2 mRNAs are affected by food availability. Tissue distribution of NUCB2A and NUCB2B mRNAs, and NUCB2/nesfatin-1-like immunoreactivity (ir) in the gut of zebrafish were also investigated. In zebrafish, nesfatin-1 region (1-82 amino acids) in NUCB2A is 78% identical to NUCB2B. Both NUCB2A and NUCB2 mRNAs were most abundant in the liver, while less expression was found in other tissues including the brain and gut. NUCB2/nesfatin-1-like immunoreactivity was detected in the mucosal layer cells of zebrafish anterior gastrointestinal tract. NUCB2A and NUCB2B mRNA expression were decreased in the brain of zebrafish 3h after feeding, and after a 7-day food deprivation. Both NUCB2A and NUCB2B mRNAs in the gut were also decreased following 7 days of food deprivation, while NUCB2B mRNA was increased in the liver. Our results provide molecular and functional evidences to support potential anorectic and metabolic roles for endogenous nesfatin-1 in zebrafish. To our knowledge, this is the first report on NUCB2B characterization in vertebrates. PMID:25260251

  14. The CDKN2A-CDKN2B rs4977756 polymorphism and glioma risk: a meta-analysis

    PubMed Central

    Lu, Hongwei; Yang, Yuantao; Wang, Jihui; Liu, Yang; Huang, Ming; Sun, Xinlin; Ke, Yiquan

    2015-01-01

    The association between the rs4977756 single nucleotide polymorphism (SNP) and glioma risk has been studied, but these studies have yielded conflicting results. In order to explore this association, we performed a meta-analysis. A comprehensive literature search was performed using PubMed and EMBASE database. Six articles including 12 case-control studies in English with 12022 controls and 6871 cases were eligible for the meta-analysis. Subgroup analyses were conducted by ethnicity and source of controls. Our meta-analysis found that rs4977756 polymorphism was associated with glioma risks in homozygote, heterozygote, dominant, recessive and additive genetic models (GG versus AA: OR=1.55, 95% CI=1.42-1.69, Ph=0.996, I2=0.0%; AG versus AA: OR=1.20, 95% CI=1.12-1.28, Ph=0.934, I2=0.0%; recessive model: OR=1.39, 95% CI=1.28-1.50, Ph=0.995, I2=0.0%; dominant model: OR=1.29, 95% CI=1.21-1.37, Ph=0.923, I2=0.0%; additive model: OR=1.24, 95% CI=1.19-1.30, Ph=0.966, I2=0.0%). Moreover, our results suggested that CDKN2A-CDKN2B rs4977756 polymorphism was associated with a notable increased risk of glioma in Europeans. However, in Asians, we could not come to a conclusion because of lack of studies. Sensitivity analysis showed the omission of any study made no significant difference. No evidence of publication bias was produced. Our meta-analysis suggested that rs4977756 polymorphism was associated with increased risk of glioma. Moreover, additional studies should be further investigated to draw a more accurate conclusion. PMID:26770338

  15. A commercial PCV2a-based vaccine significantly reduces PCV2b transmission in experimental conditions.

    PubMed

    Rose, N; Andraud, M; Bigault, L; Jestin, A; Grasland, B

    2016-07-19

    Transmission characteristics of PCV2 have been compared between vaccinated and non-vaccinated pigs in experimental conditions. Twenty-four Specific Pathogen Free (SPF) piglets, vaccinated against PCV2 at 3weeks of age (PCV2a recombinant CAP protein-based vaccine), were inoculated at 15days post-vaccination with a PCV2b inoculum (6⋅10(5) TCID50), and put in contact with 24 vaccinated SPF piglets during 42days post-inoculation. Those piglets were shared in six replicates of a contact trial involving 4 inoculated piglets mingled with 4 susceptible SPF piglets. Two replicates of a similar contact trial were made with non-vaccinated pigs. Non vaccinated animals received a placebo at vaccination time and were inoculated the same way and at the same time as the vaccinated group. All the animals were monitored twice weekly using quantitative real-time PCR and ELISA for serology until 42days post-inoculation. The frequency of infection and the PCV2 genome load in sera of the vaccinated pigs were significantly reduced compared to the non-vaccinated animals. The duration of infectiousness was significantly different between vaccinated and non-vaccinated groups (16.6days [14.7;18.4] and 26.6days [22.9;30.4] respectively). The transmission rate was also considerably decreased in vaccinated pigs (β=0.09 [0.05-0.14] compared to β=0.19 [0.11-0.32] in non-vaccinated pigs). This led to an estimated reproduction ratio of 1.5 [95% CI 0.8 - 2.2] in vaccinated animals versus 5.1 [95% CI 2.5 - 8.2] in non-vaccinated pigs when merging data of this experiment with previous trials carried out in same conditions. PMID:27318416

  16. Binding kinetics of histone chaperone Chz1 and variant histone H2A.Z-H2B by relaxation dispersion NMR spectroscopy

    PubMed Central

    Hansen, D. Flemming; Zhou, Zheng; Feng, Haniqiao; Miller Jenkins, Lisa M.; Bai, Yawen; Kay, Lewis E.

    2009-01-01

    The genome of eukaryotic cells is packed into a compact structure called chromatin that consists of DNA as well as both histone and non-histone proteins. Histone-chaperones associate with histone proteins and play important roles in the assembly of chromatin structure and transport of histones in the cell. The recently discovered histone-chaperone Chz1 associates with the variant histone H2A.Z of budding yeast and plays a critical role in the exchange of the canonical histone pair H2A-H2B for the variant H2A.Z-H2B. Here, we present an NMR approach that provides accurate estimates for the rates of association and dissociation of Chz1 and H2A.Z-H2B. The methodology exploits the fact that in a 1:1 mixture of Chz1 and H2A.Z-H2B the small amounts of unbound proteins that are invisible in spectra produce line-broadening of signals from the complex that can be quantified in terms of the thermodynamics and kinetics of the exchange process. The dissociation rate constant measured, 22±2 s−1, provides an upper bound for the rate of transfer of H2A.Z-H2B to the chromatin remodeling complex and the faster than diffusion association rate, 108±107 M−1s−1, establishes the importance of attractive electrostatic interactions that form the chaperone:histone complex. PMID:19385041

  17. MicroRNA signatures predict dysregulated vitamin D receptor and calcium pathways status in limb girdle muscle dystrophies (LGMD) 2A/2B.

    PubMed

    Aguennouz, M; Lo Giudice, C; Licata, N; Rodolico, C; Musumeci, O; Fanin, M; Migliorato, A; Ragusa, M; Macaione, V; Di Giorgio, R M; Angelini, C; Toscano, A

    2016-08-01

    miRNA expression profile and predicted pathways involved in selected limb-girdle muscular dystrophy (LGMD)2A/2B patients were investigated. A total of 187 miRNAs were dysregulated in all patients, with six miRNAs showing opposite regulation in LGMD2A versus LGMD2B patients. Silico analysis evidence: (1) a cluster of the dysregulated miRNAs resulted primarily involved in inflammation and calcium metabolism, and (2) two genes predicted as controlled by calcium-assigned miRNAs (Vitamin D Receptor gene and Guanine Nucleotide Binding protein beta polypeptide 1gene) showed an evident upregulation in LGMD2B patients, in accordance with miRNA levels. Our data support alterations in calcium pathway status in LGMD 2A/B, suggesting myofibre calcium imbalance as a potential therapeutic target. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27558075

  18. GluN2A and GluN2B subunit-containing NMDA receptors in hippocampal plasticity

    PubMed Central

    Shipton, Olivia A.; Paulsen, Ole

    2014-01-01

    N-Methyl-d-aspartate receptor (NMDAR)-dependent synaptic plasticity is a strong candidate to mediate learning and memory processes that require the hippocampus. This plasticity is bidirectional, and how the same receptor can mediate opposite changes in synaptic weights remains a conundrum. It has been suggested that the NMDAR subunit composition could be involved. Specifically, one subunit composition of NMDARs would be responsible for the induction of long-term potentiation (LTP), whereas NMDARs with a different subunit composition would be engaged in the induction of long-term depression (LTD). Unfortunately, the results from studies that have investigated this hypothesis are contradictory, particularly in relation to LTD. Nevertheless, current evidence does suggest that the GluN2B subunit might be particularly important for plasticity and may make a synapse bidirectionally malleable. In particular, we conclude that the presence of GluN2B subunit-containing NMDARs at the postsynaptic density might be a necessary, though not a sufficient, condition for the strengthening of individual synapses. This is owing to the interaction of GluN2B with calcium/calmodulin-dependent protein kinase II (CaMKII) and is distinct from its contribution as an ion channel. PMID:24298164

  19. Targeting of protein phosphatases PP2A and PP2B to the C-terminus of the L-type calcium channel Ca v1.2.

    PubMed

    Xu, Hui; Ginsburg, Kenneth S; Hall, Duane D; Zimmermann, Maike; Stein, Ivar S; Zhang, Mingxu; Tandan, Samvit; Hill, Joseph A; Horne, Mary C; Bers, Donald; Hell, Johannes W

    2010-12-01

    The L-type Ca(2+) channel Ca(v)1.2 forms macromolecular signaling complexes that comprise the β(2) adrenergic receptor, trimeric G(s) protein, adenylyl cyclase, and cAMP-dependent protein kinase (PKA) for efficient signaling in heart and brain. The protein phosphatases PP2A and PP2B are part of this complex. PP2A counteracts increase in Ca(v)1.2 channel activity by PKA and other protein kinases, whereas PP2B can either augment or decrease Ca(v)1.2 currents in cardiomyocytes depending on the precise experimental conditions. We found that PP2A binds to two regions in the C-terminus of the central, pore-forming α(1) subunit of Ca(v)1.2: one region spans residues 1795-1818 and the other residues 1965-1971. PP2B binds immediately downstream of residue 1971. Injection of a peptide that contained residues 1965-1971 and displaced PP2A but not PP2B from endogenous Ca(v)1.2 increased basal and isoproterenol-stimulated L-type Ca(2+) currents in acutely isolated cardiomyocytes. Together with our biochemical data, these physiological results indicate that anchoring of PP2A at this site of Ca(v)1.2 in the heart negatively regulates cardiac L-type currents, likely by counterbalancing basal and stimulated phosphorylation that is mediated by PKA and possibly other kinases. PMID:21053940

  20. DIFFERENTIAL ROLE OF NR2A AND NR2B NMDA RECEPTORS IN MEDIATING PHENCYCLIDINE-INDUCED PERINATAL NEURONAL APOPTOSIS AND BEHAVIORAL DEFICITS

    PubMed Central

    Anastasio, Noelle C.; Xia, Yan; O’Connor, Zoe R.; Johnson, Kenneth M.

    2009-01-01

    The mechanism underlying PCP-induced apoptosis in perinatal rats and the development of schizophrenic-like behaviors is incompletely understood. We used antagonists for NR2A- and NR2B-containing NMDARs to test the hypothesis that the behavioral and apoptotic effects of PCP are mediated by blockade of NR1/NR2A-containing receptors, rather than NR1/NR2B-containing receptors. Sprague-Dawley rats were treated on PN7, 9, and 11 with PCP (10 mg/kg), PEAQX (NR2A-preferring antagonist, 10, 20, or 40 mg/kg), or ifenprodil (selective NR2B antagonist, 1, 5, or 10 mg/kg) and sacrificed for measurement of caspase-3 activity (an index of apoptosis) or allowed to age and tested for locomotor sensitization to PCP challenge on PN28-35. PCP or PEAQX on PN7, 9, and 11 markedly elevated caspase-3 activity in the cortex; ifenprodil showed no effect. Striatal apoptosis was evident only after sub-chronic treatment with a high dose of PEAQX (20 mg/kg). Animals treated with PCP or PEAQX on PN7, 9 and 11 showed a sensitized locomotor response to PCP challenge on PN28-35. Ifenprodil treatment had no effect on either measure. Therefore, PCP blockade of cortical NR1/NR2A, rather than NR1/NR2B, appears to be responsible for PCP-induced apoptosis and the development of long-lasting behavioral deficits. PMID:19654040

  1. 77 FR 59670 - Electronic Filing of H-2A and H-2B Labor Certification Applications Through the iCERT Visa Portal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... Through the iCERT Visa Portal System AGENCY: Employment and Training Administration, Department of Labor... under the H-2A and H-2B visa programs through the Department of Labor's (Department) iCERT Visa Portal...'s Web site ( http://www.foreignlaborcert.doleta.gov/ gov/) once dates are finalized. Employers...

  2. Determination of evolutionary relationships of outbreak-associated Listeria monocytogenes strains of serotypes 1/2a and 1/2b by whole-genome sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We used whole-genome sequencing to determine evolutionary relationships among 20 outbreak-associated clinical isolates of Listeria monocytogenes serotypes 1/2a and 1/2b. Isolates from 6 of 11 outbreaks fell outside the clonal groups or “epidemic clones” that have been previously associated with outb...

  3. MacroH2A1.1 and PARP-1 cooperate to regulate transcription by promoting CBP-mediated H2B acetylation

    PubMed Central

    Chen, Hongshan; Ruiz, Penelope D.; Novikov, Leonid; Casill, Alyssa D.; Park, Jong Woo; Gamble, Matthew J.

    2014-01-01

    The histone variant macroH2A1 regulates gene expression important for differentiation, stem cell reprogramming and tumor suppression. Here, we demonstrate that in primary human cells, macroH2A1 participates in two physically and functionally distinct types of chromatin either marked by H3K27me3 or nine histone acetylations. Using RNA-seq, we found that macroH2A1-regulated genes, which have roles in cancer progression, are specifically found in macroH2A1-containing acetylated chromatin. Of the two macroH2A1 variants, macroH2A1.1 and macroH2A1.2, the former is suppressed in cancer and can interact with PARP-generated poly(ADP-ribose). Through the recruitment of PARP-1, macroH2A1.1 promotes the CBP-mediated acetylation of H2B K12 and K120 which either positively or negatively regulates the expression of macroH2A1-target genes. While macroH2A1-regulated H2B acetylation is a common feature of primary cells, this regulation is typically lost in cancer cells. Consequently, our results provide important insight into macroH2A1.1’s role in cancer suppression. PMID:25306110

  4. SmMYC2a and SmMYC2b played similar but irreplaceable roles in regulating the biosynthesis of tanshinones and phenolic acids in Salvia miltiorrhiza.

    PubMed

    Zhou, Yangyun; Sun, Wei; Chen, Junfeng; Tan, Hexin; Xiao, Ying; Li, Qing; Ji, Qian; Gao, Shouhong; Chen, Li; Chen, Shilin; Zhang, Lei; Chen, Wansheng

    2016-01-01

    Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects. PMID:26947390

  5. SmMYC2a and SmMYC2b played similar but irreplaceable roles in regulating the biosynthesis of tanshinones and phenolic acids in Salvia miltiorrhiza

    PubMed Central

    Zhou, Yangyun; Sun, Wei; Chen, Junfeng; Tan, Hexin; Xiao, Ying; Li, Qing; Ji, Qian; Gao, Shouhong; Chen, Li; Chen, Shilin; Zhang, Lei; Chen, Wansheng

    2016-01-01

    Salvia miltiorrhiza Bunge, which contains tanshinones and phenolic acids as major classes of bioactive components, is one of the most widely used herbs in traditional Chinese medicine. Production of tanshinones and phenolic acids is enhanced by methyl jasmonate (MeJA). Transcription factor MYC2 is the switch of jasmontes signaling in plants. Here, we focused on two novel JA-inducible genes in S. miltiorrhiza, designated as SmMYC2a and SmMYC2b, which were localized in the nucleus. SmMYC2a and SmMYC2b were also discovered to interact with SmJAZ1 and SmJAZ2, implying that the two MYC2s might function as direct targets of JAZ proteins. Ectopic RNA interference (RNAi)-mediated knockdown experiments suggested that SmMYC2a/b affected multiple genes in tanshinone and phenolic acid biosynthetic pathway. Besides, the accumulation of tanshinones and phenolic acids was impaired by the loss of function in SmMYC2a/b. Meanwhile, SmMYC2a could bind with an E-box motif within SmHCT6 and SmCYP98A14 promoters, while SmMYC2b bound with an E-box motif within SmCYP98A14 promoter, through which the regulation of phenolic acid biosynthetic pathway might achieve. Together, these results suggest that SmMYC2a and SmMYC2b are JAZ-interacting transcription factors that positively regulate the biosynthesis of tanshinones and Sal B with similar but irreplaceable effects. PMID:26947390

  6. Separate Fc-receptors for immunoglogulins IgG2a and IgG2b on an established cell line of mouse macrophages.

    PubMed

    Walker, W S

    1976-04-01

    The specificity of Fe-receptors on IC-21 cells, an established line of mouse peritoneal macrophages with antibody-dependent effector cell activity has been examined. Only IgG2a and IgG2b myeloma proteins bound readily to IC-21 Fc-receptors, the former in nonaggregated as well as aggregated form, the latter only as aggregated complexes. Thus, IgG2a bound in a manner characteristic of classically defined cytophilic antibody, whereas the binding of IgG2b appeared to be mediated by Fc-receptors for antigen-antibody complexes. Evidence is presented in support of the view that IC-21 macrophages possess separate and distinct Fc-receptor sites for these two immunoglobulins. PMID:1254971

  7. Structure Change from β-Strand and Turn to α-Helix in Histone H2A-H2B Induced by DNA Damage Response.

    PubMed

    Izumi, Yudai; Fujii, Kentaro; Wien, Frank; Houée-Lévin, Chantal; Lacombe, Sandrine; Salado-Leza, Daniela; Porcel, Erika; Masoud, Rawand; Yamamoto, Satoshi; Réfrégiers, Matthieu; Hervé du Penhoat, Marie-Anne; Yokoya, Akinari

    2016-07-12

    Using synchrotron radiation-based circular dichroism spectroscopy, we found that the DNA damage response induces an increase of α-helix structure and a decrease of β-strand and turn structures in histone H2A-H2B extracted from x-irradiated human HeLa cells. The structural alterations correspond to the assumption that an average of eight amino acid residues form new α-helix structures at 310 K. We propose the structural transition from β-strand and turn structures to an α-helix structure in H2A-H2B as a novel, to our knowledge, process involved in the DNA damage response. PMID:27410735

  8. Increased expression of 5-HT(2A) and 5-HT(2B) receptors in detrusor muscle after partial bladder outlet obstruction in rats.

    PubMed

    Michishita, Mai; Yano, Kazuo; Kasahara, Ken-ichi; Tomita, Ken-ichi; Matsuzaki, Osamu

    2015-01-01

    Serotonin (5-hydroxytryptamine; 5-HT)-induced bladder contraction is enhanced after partial bladder outlet obstruction (pBOO) in rats. We investigated time-dependent changes in bladder contraction and expression of 5-HT(2A) and 5-HT(2B) receptor mRNA in bladder tissue to elucidate the mechanism of this enhancement. On day 3 and 7 after pBOO, contractile responses of isolated rat bladder strips to 5-HT were increased compared with that in sham-operated rats; on day 14, the response had decreased to the same level as that in sham rat bladders. In contrast, carbacholinduced contraction was not enhanced by pBOO at any time point. In sham rats, 5-HT(2A) receptor mRNA was expressed in the urothelium, and 5-HT(2B) receptor mRNA was expressed in the detrusor muscle layer. In pBOO rats, both receptor mRNAs were increased in the detrusor muscle and subserosal layers, but not in the urothelium. The increase of 5-HT(2A) receptor mRNA was maintained from day 3 to day 14 after pBOO, and 5-HT(2B) receptor mRNA was increased on day 7 after pBOO. These results suggested that pBOO induced up-regulation of the 5-HT(2A) and 5-HT(2B) receptors in the detrusor muscle and subserosal layers of the bladder, and such up-regulation may be related to the enhanced bladder contractile response to 5-HT. PMID:26106048

  9. Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression

    PubMed Central

    Feyissa, Anteneh M.; Zyga, Agata; Stockmeier, Craig A.; Karolewicz, Beata

    2009-01-01

    Recent neuroimaging and postmortem studies have demonstrated abnormalities in glutamatergic transmission in major depression. Glutamate NMDA (N-methyl-D-aspartate) receptors are one of the major mediators of excitatory neurotransmission in the central nervous system. At synaptic sites, NMDA receptors are linked with postsynaptic density protein-95 (PSD-95) that plays a key role in mediating trafficking, clustering, and downstream signaling events, following receptor activation. In this study, we examined the expression of NMDA receptor subunits NR1, NR2A, and NR2B as well as PSD-95 in the anterior prefrontal cortex (PFC) using Western blot method. Cortical samples were obtained from age, gender and postmortem interval matched depressed and psychiatrically healthy controls. The results revealed that there was a reduced expression of the NMDA receptor subunits NR2A (−54%) and NR2B (−48%), and PSD-95 protein level (−40%) in the PFC of depressed subjects relative to controls, with no change in the NR1 subunit. The alterations in NMDA receptor subunits, especially the NR2A and NR2B, as well as PSD-95 suggest an abnormality in the NMDA receptor signaling in the PFC in major depression. Our findings in conjunction with recent clinical, cellular, and neuroimaging studies further implicate the involvement of glutamate neurotransmission in the pathophysiology of depression. This study provides additional evidence that NMDA receptor complex is a target for discovery of novel antidepressants. PMID:18992785

  10. Ultraviolet Photodissociation Dynamics of the Allyl Radical via the B̃(2)A1(3s), C̃(2)B2(3py), and Ẽ(2)B1(3px) Electronic Excited States.

    PubMed

    Song, Yu; Lucas, Michael; Alcaraz, Maria; Zhang, Jingsong; Brazier, Christopher

    2015-12-17

    Ultraviolet (UV) photodissociation dynamics of jet-cooled allyl radical via the B̃(2)A1(3s), C̃(2)B2(3py), and Ẽ(2)B1(3px) electronically excited states are studied at the photolysis wavelengths from 249 to 216 nm using high-n Rydberg atom time-of-flight (HRTOF) and resonance-enhanced multiphoton ionization (REMPI) techniques. The photofragment yield (PFY) spectra of the H atom products are measured using both allyl chloride and 1,5-hexadiene as precursors of the allyl radical and show a broad peak centered near 228 nm, whereas the previous UV absorption spectra of the allyl radical peak around 222 nm. This difference suggests that, in addition to the H + C3H4 product channel, another dissociation channel (likely CH3 + C2H2) becomes significant with increasing excitation energy. The product translational energy release of the H + C3H4 products is modest, with the P(ET) distributions peaking near 8.5 kcal/mol and the fraction of the average translational energy in the total excess energy, ⟨fT⟩, in the range 0.22-0.18 from 249 to 216 nm. The P(ET)'s are consistent with production of H + allene and H + propyne, as suggested by previous experimental and theoretical studies. The angular distributions of the H atom products are isotropic, with the anisotropy parameter β ≈ 0. The H atom dissociation rate constant from the pump-probe study gives a lower limit of 1 × 10(8)/s. The dissociation mechanism is consistent with unimolecular decomposition of the hot allyl radical on the ground electronic state after internal conversion of the electronically excited state. PMID:26334360

  11. PPARγ Ligands Switched High Fat Diet-Induced Macrophage M2b Polarization toward M2a Thereby Improving Intestinal Candida Elimination

    PubMed Central

    Olagnier, David; Bernad, José; Perez, Laurence; Burcelin, Rémy; Valentin, Alexis; Auwerx, Johan; Pipy, Bernard; Coste, Agnès

    2010-01-01

    Obesity is associated with a chronic low-grade inflammation that predisposes to insulin resistance and the development of type 2 diabetes. In this metabolic context, gastrointestinal (GI) candidiasis is common. We recently demonstrated that the PPARγ ligand rosiglitazone promotes the clearance of Candida albicans through the activation of alternative M2 macrophage polarization. Here, we evaluated the impact of high fat diet (HFD)-induced obesity and the effect of rosiglitazone (PPARγ ligand) or WY14643 (PPARα ligand) both on the phenotypic M1/M2 polarization of peritoneal and cecal tissue macrophages and on the outcome of GI candidiasis. We demonstrated that the peritoneal macrophages and the cell types present in the cecal tissue from HF fed mice present a M2b polarization (TNF-αhigh, IL-10high, MR, Dectin-1). Interestingly, rosiglitazone induces a phenotypic M2b-to-M2a (TNF-αlow, IL-10low, MRhigh, Dectin-1high) switch of peritoneal macrophages and of the cells present in the cecal tissue. The incapacity of WY14643 to switch this polarization toward M2a state, strongly suggests the specific involvement of PPARγ in this mechanism. We showed that in insulin resistant mice, M2b polarization of macrophages present on the site of infection is associated with an increased susceptibility to GI candidiasis, whereas M2a polarization after rosiglitazone treatment favours the GI fungal elimination independently of reduced blood glucose. In conclusion, our data demonstrate a dual benefit of PPARγ ligands because they promote mucosal defence mechanisms against GI candidiasis through M2a macrophage polarization while regulating blood glucose level. PMID:20877467

  12. Increased NR2A:NR2B ratio compresses long-term depression range and constrains long-term memory.

    PubMed

    Cui, Zhenzhong; Feng, Ruiben; Jacobs, Stephanie; Duan, Yanhong; Wang, Huimin; Cao, Xiaohua; Tsien, Joe Z

    2013-01-01

    The NR2A:NR2B subunit ratio of the NMDA receptors is widely known to increase in the brain from postnatal development to sexual maturity and to aging, yet its impact on memory function remains speculative. We have generated forebrain-specific NR2A overexpression transgenic mice and show that these mice had normal basic behaviors and short-term memory, but exhibited broad long-term memory deficits as revealed by several behavioral paradigms. Surprisingly, increased NR2A expression did not affect 1-Hz-induced long-term depression (LTD) or 100 Hz-induced long-term potentiation (LTP) in the CA1 region of the hippocampus, but selectively abolished LTD responses in the 3-5 Hz frequency range. Our results demonstrate that the increased NR2A:NR2B ratio is a critical genetic factor in constraining long-term memory in the adult brain. We postulate that LTD-like process underlies post-learning information sculpting, a novel and essential consolidation step in transforming new information into long-term memory. PMID:23301157

  13. Expression and activity of cytochromes P450 2E1, 2A, and 2B in the mouse ovary: the effect of 4-vinylcyclohexene and its diepoxide metabolite.

    PubMed

    Cannady, Ellen A; Dyer, Cheryl A; Christian, Patricia J; Sipes, I Glenn; Hoyer, Patricia B

    2003-06-01

    4-Vinylcyclohexene (VCH), an occupational chemical, causes destruction of small preantral follicles (F1) in mice. Previous studies suggested that VCH is bioactivated via cytochromes P450 (CYP450) to the ovotoxic, diepoxide metabolite, VCD. Whereas hepatic CYP450 isoforms 2E1, 2A, and 2B can metabolize VCH, the role of ovarian metabolism is unknown. This study investigated expression of these isoforms in isolated ovarian fractions (F1, 25-100 microm; F2, 100-250 microm; F3, >250 microm; interstitial cells, Int) from B6C3F1 mice dosed daily (15 days; ip) with vehicle, VCH (7.4 mmol/kg/day) or VCD (0.57 mmol/kg/day). Ovaries were removed and either isolated into specific ovarian compartments for mRNA analysis, fixed for immunohistochemistry, or prepared for enzymatic assays. mRNA and protein for all isoforms were expressed/distributed in all ovarian fractions from vehicle-treated mice. In the targeted F1 follicles, VCH or VCD dosing increased (p < 0.05) mRNA encoding CYP2E1 (645 +/- 14% VCH; 582 +/- 16% VCD), CYP2A (689 +/- 8% VCH; 730 +/- 22% VCD), and CYP2B (246 +/- 7% VCH) above control. VCH dosing altered (p < 0.05) mRNA encoding CYP2E1 in nontargeted F3 follicles (168 +/- 7%) and CYP2A in Int (207 +/- 19%) above control. Immunohistochemical analysis revealed the greatest staining intensity for all CYP isoforms in the Int. VCH dosing altered (p < 0.05) staining intensity in Int for CYP2E1 (19 +/- 2.4% below control) and CYP2A (39 +/- 5% above control). Staining intensity for CYP2B was increased (p < 0.05) above control in granulosa cells of small preantral (187 +/- 42%) and antral (63 +/- 8%) follicles. Catalytic assays in ovarian homogenates revealed that CYP2E1 and CYP2B were functional. Only CYP2E1 activity was increased (149 +/- 12% above control; p < 0.05) by VCH dosing. The results demonstrate that mRNA and protein for CYP isoforms known to bioactivate VCH are expressed in the mouse ovary and are modulated by in vivo exposure to VCH and VCD. Interestingly

  14. Adenosine A(1), A(2a), A(2b), and A(3) receptors in hematopoiesis. 1. Expression of receptor mRNA in four mouse hematopoietic precursor cells.

    PubMed

    Streitová, D; Sefc, L; Savvulidi, F; Pospísil, M; Holá, J; Hofer, M

    2010-01-01

    Four mouse bone marrow or thymus cell populations, namely granulopoietic/monocytopoietic, erythropoietic, B-lymphopoietic, and T-lymphopoietic precursor cells have been assayed by RT-PCR technique for the presence and relative amounts of adenosine A(1), A(2a), A(2b), and A(3) receptor mRNA. It has been found that (i) all four populations studied express all four adenosine receptor subtypes, (ii) the A(1), receptor is the least expressed in all populations studied, (iii) the A(3) receptor is markedly expressed in the populations of granulopoietic/monocytopoietic and erythropoietic cells, (iv) the A(2a) receptor is markedly expressed in the populations of B-lymphopoietic and T-lymphopoietic cells, and v) the A(2b) receptor does not predominate in any of the precursor cells studied. Our data offer a new possibility for the assessment of the readiness of these cells to respond, by receptor-mediated mechanisms, to adenosine or its analogs present in the tissues as a result of endogenous processes and/or following their administration. PMID:19249907

  15. The α2-adrenoceptors mediating inhibition of the vasopressor sympathetic outflow in pithed rats: pharmacological correlation with α2A, α2B and α2C subtypes.

    PubMed

    Villamil-Hernández, Ma Trinidad; Alcántara-Vázquez, Oscar; Sánchez-López, Araceli; Centurión, David

    2013-10-15

    α2-Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In vitro studies have confirmed that α2A, α2B and α2C subtypes inhibited noradrenaline release from postganglionic sympathetic neurons but no study has been reported their involvement in the vasopressor sympathetic outflow in vivo. Thus, this study analysed the subtype(s) involved in the inhibition produced by the α2-adrenoceptor agonist, B-HT 933, on the vasopressor sympathetic outflow. Male Wistar pithed rats were pre-treated with i.v. bolus injections of gallamine (25mg/kg) and desipramine (50 µg/kg) and prepared to stimulate the vasopressor sympathetic outflow (T7-T9) or to receive i.v. bolus of exogenous noradrenaline. Sympathetic stimulation or exogenous noradrenaline produced, respectively, frequency-dependent and dose-dependent vasopressor responses. I.v. continuous infusion of B-HT 933 (30 μg/kg min) failed to modify the vasopressor responses to exogenous noradrenaline and inhibited those induced by preganglionic stimulation of the vasopressor sympathetic outflow at all frequencies of stimulation (0.03-3 Hz). The sympatho-inhibition elicited by B-HT 933 was: (i) unaffected by vehicles (1 ml/kg); (ii) partially antagonised by BRL44408 (300 μg/kg; α2A), imiloxan (3000 μg/kg; α2B) and/or JP-1302 (300 μg/kg; α2C) given separately; and (iii) completely blocked by rauwolscine (300 μg/kg) or the combination of BRL44408 (300 μg/kg)+imiloxan (3000 μg/kg)+JP-1302 (300 μg/kg). The above doses of antagonists did not modify per se the sympathetically-induced vasopressor responses. These results suggest that the vasopressor sympatho-inhibition to B-HT 933 is primarily mediated by activation of α2A/2B/2C-adrenoceptors in pithed rats. PMID:24028939

  16. Differential roles of GluN2A- and GluN2B-containing NMDA receptors in neuronal survival and death

    PubMed Central

    Lujan, Brendan; Liu, Xiaoxuan; Wan, Qi

    2012-01-01

    Glutamate-induced neurotoxicity is the primary molecular mechanism that induces neuronal death in a variety of pathologies in central nervous system (CNS). Toxicity signals are relayed from extracellular space to the cytoplasm by N-methyl-D-aspartate receptors (NMDARs) and regulate a variety of survival and death signaling. Differential subunit combinations of NMDARs confer neuroprotection or trigger neuronal death pathways depending on the subunit arrangements of NMDARs and its localization on the cell membrane. It is well-known that GluN2B-contaning NMDARs (GluN2BRs) preferentially link to signaling cascades involved in CNS injury promoting neuronal death and neurodegeneration. Conversely, less well-known mechanisms of neuronal survival signaling are associated with GluN2A-comtaining NMDARs (GluN2AR)-dependent signal pathways. This review will discuss the most recent signaling cascades associated with GluN2ARs and GluN2BRs. PMID:23320134

  17. Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

    PubMed Central

    Michel, Anne; Downey, Patrick; Nicolas, Jean-Marie; Scheller, Dieter

    2014-01-01

    In Parkinson's disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients. PMID:25513815

  18. The relative cellular levels of CP2a and CP2b potentiates erythroid cell-specific expression of the {alpha}-globin gene by regulating the nuclear localization of CP2c

    SciTech Connect

    Chae, Ji Hyung; Kang, Ho Chul; Kim, Chul Geun

    2009-03-20

    CP2b activates {alpha}-globin expression in an erythroid cell-specific manner, through interaction with CP2c and PIAS1. Although CP2a is identical to CP2b except for lacking an exon encoding additional 36 amino acids and has the intrinsic DNA binding and transactivation properties, it does not exert any role in {alpha}-globin expression. Investigation of subcellular localization of exogenous CP2 proteins revealed that CP2a and CP2b were exclusively localized in the cytosol and nucleus, respectively. The CP2b-specific exon was in charge of the nuclear localization of CP2b. Interestingly, subcellular localization of CP2c was either in the nucleus or cytosol depending on the relative level of CP2a and CP2b although CP2c intrinsically localized in the cytosol in the absence of CP2a/CP2b. Finally, dramatic increment of hemoglobin expression was correlated with nuclear translocation of CP2c during MEL cell differentiation. Our data suggest that CP2b potentiate erythroid cell-specific {alpha}-globin expression by recruiting CP2c into the nucleus.

  19. Canonical histone H2Ba and H2A.X dimerize in an opposite genomic localization to H2A.Z/H2B.Z dimers in Toxoplasma gondii

    PubMed Central

    Bogado, Silvina S.; Dalmasso, Carolina; Ganuza, Agustina; Kim, Kami; Sullivan, William J.; Angel, Sergio O.; Vanagas, Laura

    2014-01-01

    Histone H2Ba of Toxoplasma gondii was expressed as recombinant protein (rH2Ba) and used to generate antibody in mouse that is highly specific. Antibody recognizing rH2Ba detects a single band in tachyzoite lysate of the expected molecular weight (12 kDa). By indirect immunofluorescence (IFA) in in vitro grown tachyzoites and bradyzoites, the signal was detected only in the parasite nucleus. The nucleosome composition of H2Ba was determined through co-immunoprecipitation assays. H2Ba was detected in the same immunocomplex as H2A.X, but not with H2A.Z. Through chromatin immunoprecipitation (ChIP) assays and qPCR, it was observed that H2Ba is preferentially located at promoters of inactive genes and silent regions, accompanying H2A.X and opposed to H2A.Z/H2B.Z dimers. PMID:25286383

  20. A study of presynaptic alpha2-autoreceptors in alpha2A/D-, alpha2B- and alpha2C-adrenoceptor-deficient mice.

    PubMed

    Trendelenburg, A U; Klebroff, W; Hein, L; Starke, K

    2001-08-01

    The function of presynaptic alpha2-autoreceptors was studied in the hippocampus, occipito-parietal cortex, atria and vas deferens of NMRI mice, mice in which the alpha2A/D-, the alpha2B- or alpha2c-adrenoceptor gene had been disrupted (alpha2A/DKO, alpha2BKO and alpha2CKO, respectively), and the wildtype mice from which the knockout animals had been generated. Tissue pieces were preincubated with 3H-noradrenaline and then superfused and stimulated electrically. The alpha2-adrenoceptor agonist medetomidine reduced the electrically evoked overflow of tritium in all tissues from all mouse strains (stimulation with single pulses or single high-frequency pulse trains, called POPs, i.e. pulse patterns leading to minimal autoinhibition). The effects of medetomidine did not differ in NMRI, wildtype, alpha2BKO and alpha2CKO mice but were greatly reduced in alpha2A/DKO brain preparations and to a lesser extent in alpha2A/DKO atria and vasa deferentia. Six drugs were tested as antagonists against medetomidine. Their pKd values indicated that the hippocampal and occipito-parietal alpha2-autoreceptors in NMRI and wildtype mice were alpha2D (the rodent variant of the alpha2A/D-adrenoceptor) whereas the atrial and vas deferens alpha2-autoreceptors in NMRI and wildtype mice could not be identified with a single alpha2 subtype. Deletion of the alpha2A/D gene changed the pKd values in all tissues so that they now reflected alpha2C properties, whereas deletion of the alpha2C gene changed the pKd values in atria and vasa deferentia so that they now had alpha2D properties (as they had in NMRI and wildtype brain preparations). Autoinhibition by released noradrenaline was created using trains of up to 64 pulses or up to 4 POPs, and the overflow-enhancing effect of the alpha2 antagonist rauwolscine was determined. Results did not differ, irrespective of whether preparations were obtained from NMRI, wildtype, alpha2BKO or alpha2CKO mice: the overflow of tritium elicited by p pulses or POPs

  1. Breadth of neutralization and synergy of clinically relevant human monoclonal antibodies against HCV genotypes 1a, 1b, 2a, 2b, 2c, and 3a

    PubMed Central

    Carlsen, Thomas H.R.; Pedersen, Jannie; Prentoe, Jannick C.; Giang, Erick; Keck, Zhen-Yong; Mikkelsen, Lotte S.; Law, Mansun; Foung, Steven K. H.; Bukh, Jens

    2015-01-01

    Human monoclonal antibodies (HMAbs) with neutralizing capabilities constitute potential immune-based treatments or prophylaxis against hepatitis C virus (HCV). However, lack of cell culture-derived HCV (HCVcc) harboring authentic envelope proteins (E1/E2) has hindered neutralization investigations across genotypes, subtypes, and isolates. We investigated the breadth of neutralization of 10 HMAbs with therapeutic potential against a panel of 16 JFH1-based HCVcc expressing patient-derived Core-NS2 from genotypes 1a (strains H77, TN, and DH6), 1b (J4, DH1, and DH5), 2a (J6, JFH1, and T9), 2b (J8, DH8, and DH10), 2c (S83), and 3a (S52, DBN, and DH11). Virus stocks used for in vitro neutralization analysis contained authentic E1/E2, with the exception of full-length JFH1 that acquired the N417S substitution in E2. The 50% inhibition concentration (IC50) for each HMAb against the HCVcc panel was determined by dose-response neutralization assays in Huh7.5 cells with antibody concentrations ranging from 0.0012 to 100 μg/ml. Interestingly, IC50-values against the different HCVcc’s exhibited large variations among the HMAbs, and only three HMAbs (HC-1AM, HC84.24, and AR4A) neutralized all 16 HCVcc recombinants. Furthermore, the IC50-values for a given HMAb varied greatly with the HCVcc strain, which supports the use of a diverse virus panel. In cooperation analyses, HMAbs HC84.24, AR3A, and, especially HC84.26, demonstrated synergistic effects towards the majority of the HCVcc’s when combined individually with AR4A. Conclusion: Through a neutralization analysis of 10 clinically relevant HMAbs against 16 JFH1-based Core-NS2 recombinants from genotypes 1a, 1b, 2a, 2b, 2c, and 3a, we identified at least 3 HMAbs with potent and broad neutralization potential. The neutralization synergism obtained when pooling the most potent HMAbs could have significant implications for developing novel strategies to treat and control HCV. PMID:25043937

  2. 76 FR 60518 - Notice of Discontinuation of H-2A and H-2B Temporary Worker Visa Exit Program Pilot CBP Dec. 11-16

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... temporary workers at certain designated ports of entry effective August 1, 2009.\\1\\ 73 FR 77049. \\1\\ The H... Pilot to Include H-2B Temporary Workers.'' 73 FR 77817.\\2\\ \\2\\ The H-2B nonimmigrant classification... Worker Visa Exit Program Pilot until December 8, 2009. 74 FR 42909. The pilot has been operating for...

  3. Bulk and mechanical properties of the Paintbrush tuff recovered from boreholes UE25 NRG-2, 2A, 2B, and 3: Data report

    SciTech Connect

    Boyd, P.J.; Martin, R.J.; Noel, J.S.; Price, R.H.

    1996-09-01

    An integral part of the licensing procedure for the potential nuclear waste repository at Yucca Mountain, Nevada, involves characterization of the in situ rheology for the design and construction of the facility and the emplacement of canisters containing radioactive waste. The data used to model the thermal and mechanical behavior of the repository and surrounding lithologies include dry and saturated bulk densities, average grain density, porosity, compressional and shear wave velocities, elastic moduli, and compressional and tensional fracture strengths. In this study, a suite of experiments was performed on cores recovered from boreholes UE25 NRG-2, 2A, 2B, and 3 drilled in support of the Exploratory Studies Facility (ESF) at Yucca Mountain. The holes penetrated the Timber Mountain tuff and two thermal/mechanical units of the Paintbrush tuff. The thermal/mechanical stratigraphy was defined by Ortiz to group rock horizons of similar properties for the purpose of simplifying modeling efforts. The relationship between the geologic stratigraphy and the thermal/mechanical stratigraphy for each borehole is presented. The tuff samples in this study have a wide range of welding characteristics (usually reflected in sample porosity), and a smaller range of mineralogy and petrology characteristics. Generally, the samples are silicic, ash-fall tuffs that exhibit large variability in their elastic and strength properties.

  4. 49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  5. 49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  6. 49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  7. 49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  8. 49 CFR Figure 2a to Subpart B of... - Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Example of an Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements-§§ 238.113 and 238.114 2A Figure 2A to... Intermediate Level Seating Area of a Multi-Level Car Complying With Window Location Requirements—§§ 238.113...

  9. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology

    PubMed Central

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S.; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  10. Intrahippocampal Administration of Ibotenic Acid Induced Cholinergic Dysfunction via NR2A/NR2B Expression: Implications of Resveratrol against Alzheimer Disease Pathophysiology.

    PubMed

    Karthick, Chennakesavan; Periyasamy, Sabapathy; Jayachandran, Kesavan S; Anusuyadevi, Muthuswamy

    2016-01-01

    Although several drugs revealed moderate amelioration of symptoms, none of them have sufficient potency to prevent or reverse the progression toward Alzheimer's disease (AD) pathology. Resveratrol (RSV), a polyphenolic compound has shown an outstanding therapeutic effect on a broad spectrum of diseases like age-associated neurodegeneration, inflammation etc. The present study was thus conducted to assess the therapeutic efficacy of RSV in ameliorating the deleterious effects of Ibotenic acid (IBO) in male Wistar rats. Stereotactic intrahippocampal administration of IBO (5 μg/μl) lesioned rats impairs cholinergic transmission, learning and memory performance that is rather related to AD and thus chosen as a suitable model to understand the drug efficacy in preventing AD pathophysiology. Since IBO is an agonist of glutamate, it is expected to exhibit an excitotoxic effect by altering glutamatergic receptors like NMDA receptor. The current study displayed significant alterations in the mRNA expression of NR2A and NR2B subunits of NMDA receptors, and further it is surprising to note that cholinergic receptors decreased in expression particularly α7-nAChR with increased m1AChR. RSV administration (20 mg/kg body weight, i.p.) significantly reduced these changes in IBO induced rats. Glutamatergic and cholinergic receptor alterations were associated with significant changes in the behavioral parameters of rats induced by IBO. While RSV improved spatial learning performance, attenuated immobility, and improvised open field activity in IBO induced rats. NR2B activation in the present study might mediate cell death through oxidative stress that form the basis of abnormal behavioral pattern in IBO induced rats. Interestingly, RSV that could efficiently encounter oxidative stress have significantly decreased stress markers viz., nitrite, PCO, and MDA levels by enhancing antioxidant status. Histopathological analysis displayed significant reduction in the hippocampal

  11. Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population.

    PubMed

    Iwasaki, Masahiko; Yoshimura, Yoshinobu; Asahi, Satoru; Saito, Kimitoshi; Sakai, Shuichi; Morita, Shigemichi; Takenaka, Osamu; Inoda, Toshio; Kashiyama, Eiji; Aoyama, Akinori; Nakabayashi, Takeshi; Omori, Satoshi; Kuwabara, Takashi; Izumi, Takashi; Nakamura, Kouichi; Takanaka, Kaoru; Nakayama, Yukiharu; Takeuchi, Mitsuaki; Nakamura, Hideki; Kametani, Shunichi; Terauchi, Yoshiaki; Hashizume, Takanori; Nagayama, Sekio; Kume, Toshiyuki; Achira, Meguru; Kawai, Hiroyuki; Kawashiro, Takashi; Nakamura, Akio; Nakai, Yasuhiro; Kagayama, Akira; Shiraga, Toshifumi; Niwa, Takuro; Yoshimura, Takuya; Morita, Jun; Ohsawa, Fukuichi; Tani, Masato; Osawa, Nobuo; Ida, Keiichi; Noguchi, Kiyoshi

    2004-12-01

    As a part of the studies conducted by the Pharma SNPs Consortium (PSC), the enzyme activities of CYP1A2, CYP2A6 and CYP2B6 variants with altered amino acids as a result of single nucleotide polymorphisms (SNPs) found among the Japanese population were analyzed under a unified protocol using the same lots of reagents by the laboratories participating in the PSC. Mutations in CYP1A2, CYP2A6 and CYP2B6 were introduced by site-directed mutagenesis and the wild type and mutated CYP molecules were expressed in Escherichia coli. The expressed cytochrome P450s were purified and the enzyme activities were measured in reconstitution systems. CYP1A2 and CYP1A2Gln478His did not show any differences in 7-ethoxyresorufin O-deethylase activity. CYP2A6 and CYP2A6Glu419Asp metabolized coumarin to form 7-hydroxycoumarin in a similar manner, whereas CYP2A6Ile471Thr showed low activity compared to the wild-type CYP2A6. CYP2B6, CYP2B6Pro167Ala and CYP2B6Arg487Cys showed the same activity for 7-ethoxy-4-triflouromethyl-coumarin O-deethylation. However, CYP2B6Gln172His was roughly twice as active as CYP2B6 and the other CYP2B6 variants for 7-ethoxy-4-triflouromethylcoumarin O-deethylation activity. Although higher inter- and intra-laboratory variations were observed for the calculated Km and V(max) values because the studies were conducted in several different laboratories, the degree of variations was reduced by the increased number of analyses and the adoption of a simple analysis system. PMID:15681899

  12. Determination of Evolutionary Relationships of Outbreak-Associated Listeria monocytogenes Strains of Serotypes 1/2a and 1/2b by Whole-Genome Sequencing

    PubMed Central

    Bergholz, Teresa M.; den Bakker, Henk C.; Katz, Lee S.; Silk, Benjamin J.; Jackson, Kelly A.; Kucerova, Zuzana; Joseph, Lavin A.; Turnsek, Maryann; Gladney, Lori M.; Halpin, Jessica L.; Xavier, Karen; Gossack, Joseph; Ward, Todd J.; Frace, Michael

    2015-01-01

    We used whole-genome sequencing to determine evolutionary relationships among 20 outbreak-associated clinical isolates of Listeria monocytogenes serotypes 1/2a and 1/2b. Isolates from 6 of 11 outbreaks fell outside the clonal groups or “epidemic clones” that have been previously associated with outbreaks, suggesting that epidemic potential may be widespread in L. monocytogenes and is not limited to the recognized epidemic clones. Pairwise comparisons between epidemiologically related isolates within clonal complexes showed that genome-level variation differed by 2 orders of magnitude between different comparisons, and the distribution of point mutations (core versus accessory genome) also varied. In addition, genetic divergence between one closely related pair of isolates from a single outbreak was driven primarily by changes in phage regions. The evolutionary analysis showed that the changes could be attributed to horizontal gene transfer; members of the diverse bacterial community found in the production facility could have served as the source of novel genetic material at some point in the production chain. The results raise the question of how to best utilize information contained within the accessory genome in outbreak investigations. The full magnitude and complexity of genetic changes revealed by genome sequencing could not be discerned from traditional subtyping methods, and the results demonstrate the challenges of interpreting genetic variation among isolates recovered from a single outbreak. Epidemiological information remains critical for proper interpretation of nucleotide and structural diversity among isolates recovered during outbreaks and will remain so until we understand more about how various population histories influence genetic variation. PMID:26590286

  13. Human CIA2A (FAM96A) and CIA2B (FAM96B) integrate maturation of different subsets of cytosolic-nuclear iron-sulfur proteins and iron homeostasis

    PubMed Central

    Stehling, Oliver; Mascarenhas, Judita; Vashisht, Ajay A.; Sheftel, Alex D.; Niggemeyer, Brigitte; Rösser, Ralf; Pierik, Antonio J.; Wohlschlegel, James A.; Lill, Roland

    2013-01-01

    SUMMARY Numerous cytosolic and nuclear proteins involved in metabolism, DNA maintenance, protein translation, or iron homeostasis depend on iron-sulfur (Fe/S) cofactors, yet their assembly is poorly defined. Here, we identify and characterize human CIA2A (FAM96A), CIA2B (FAM96B), and CIA1 (CIAO1) as components of the cytosolic Fe/S protein assembly (CIA) machinery. CIA1 associates with either CIA2A or CIA2B and the CIA targeting factor MMS19. The CIA2B-CIA1-MMS19 complex binds to and facilitates assembly of most cytosolic-nuclear Fe/S proteins. In contrast, CIA2A specifically matures iron regulatory protein (IRP) 1 which is critical for cellular iron homeostasis. Surprisingly, a second layer of iron regulation involves the stabilization of IRP2 by CIA2A binding or upon depletion of CIA2B or MMS19, even though IRP2 lacks a Fe/S cluster. In summary, CIA2B-CIA1-MMS19 and CIA2A-CIA1 assist different branches of Fe/S protein assembly, and intimately link this process to cellular iron regulation via IRP1 Fe/S cluster maturation and IRP2 stabilization. PMID:23891004

  14. Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.

    PubMed

    Crow, Yanick J; Chase, Diana S; Lowenstein Schmidt, Johanna; Szynkiewicz, Marcin; Forte, Gabriella M A; Gornall, Hannah L; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S; Abdel-Salam, Ghada M; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M; Bahi-Buisson, Nadia; Bailey, Kathryn M; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W; Bernard, Geneviève; Bianchi, Marika; Billette de Villemeur, Thierry; Blair, Edward M; Bloom, Miriam; Burlina, Alberto B; Carpanelli, Maria Luisa; Carvalho, Daniel R; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E; Chitayat, David A; Collins, Abigail E; Sierra Corcoles, Concepcion; Cordeiro, Nuno J V; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C; D'Arrigo, Stefano; De Goede, Christian G E L; De Laet, Corinne; De Waele, Liesbeth M H; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C; Fazzi, Elisa; Ferrie, Colin D; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D; Kirk, Edwin P; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J; Lin, Jean-Pierre S-M; Linnankivi, Tarja; Mackay, Mark T; Marom, Daphna R; Marques Lourenço, Charles; McKee, Shane A; Moroni, Isabella; Morton, Jenny E V; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J; Olivieri, Ivana; Ostergaard, John R; Pérez-Dueñas, Belén; Prendiville, Julie S; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A; Sinha, Gyanranjan P; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I; Straussberg, Rachel; Swoboda, Kathryn J; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y; te Water Naude, Johann; Wee Teik, Keng; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B; Wassmer, Evangeline; Webb, Hannah J; Whitehouse, William P; Whitney, Robyn N; Zaki, Maha S; Zuberi, Sameer M; Livingston, John H; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I

    2015-02-01

    Aicardi-Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi-Goutières syndrome-related genes

  15. Characterization of Human Disease Phenotypes Associated with Mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1

    PubMed Central

    Crow, Yanick J.; Chase, Diana S.; Schmidt, Johanna Lowenstein; Szynkiewicz, Marcin; Forte, Gabriella M.A.; Gornall, Hannah L.; Oojageer, Anthony; Anderson, Beverley; Pizzino, Amy; Helman, Guy; Abdel-Hamid, Mohamed S.; Abdel-Salam, Ghada M.; Ackroyd, Sam; Aeby, Alec; Agosta, Guillermo; Albin, Catherine; Allon-Shalev, Stavit; Arellano, Montse; Ariaudo, Giada; Aswani, Vijay; Babul-Hirji, Riyana; Baildam, Eileen M.; Bahi-Buisson, Nadia; Bailey, Kathryn M.; Barnerias, Christine; Barth, Magalie; Battini, Roberta; Beresford, Michael W.; Bernard, Geneviève; Bianchi, Marika; de Villemeur, Thierry Billette; Blair, Edward M.; Bloom, Miriam; Burlina, Alberto B.; Carpanelli, Maria Luisa; Carvalho, Daniel R.; Castro-Gago, Manuel; Cavallini, Anna; Cereda, Cristina; Chandler, Kate E.; Chitayat, David A.; Collins, Abigail E.; Corcoles, Concepcion Sierra; Cordeiro, Nuno J.V.; Crichiutti, Giovanni; Dabydeen, Lyvia; Dale, Russell C.; D’Arrigo, Stefano; De Goede, Christian G.E.L.; De Laet, Corinne; De Waele, Liesbeth M.H.; Denzler, Ines; Desguerre, Isabelle; Devriendt, Koenraad; Di Rocco, Maja; Fahey, Michael C.; Fazzi, Elisa; Ferrie, Colin D.; Figueiredo, António; Gener, Blanca; Goizet, Cyril; Gowrinathan, Nirmala R.; Gowrishankar, Kalpana; Hanrahan, Donncha; Isidor, Bertrand; Kara, Bülent; Khan, Nasaim; King, Mary D.; Kirk, Edwin P.; Kumar, Ram; Lagae, Lieven; Landrieu, Pierre; Lauffer, Heinz; Laugel, Vincent; La Piana, Roberta; Lim, Ming J.; Lin, Jean-Pierre S.-M.; Linnankivi, Tarja; Mackay, Mark T.; Marom, Daphna R.; Lourenço, Charles Marques; McKee, Shane A.; Moroni, Isabella; Morton, Jenny E.V.; Moutard, Marie-Laure; Murray, Kevin; Nabbout, Rima; Nampoothiri, Sheela; Nunez-Enamorado, Noemi; Oades, Patrick J.; Olivieri, Ivana; Ostergaard, John R.; Pérez-Dueñas, Belén; Prendiville, Julie S.; Ramesh, Venkateswaran; Rasmussen, Magnhild; Régal, Luc; Ricci, Federica; Rio, Marlène; Rodriguez, Diana; Roubertie, Agathe; Salvatici, Elisabetta; Segers, Karin A.; Sinha, Gyanranjan P.; Soler, Doriette; Spiegel, Ronen; Stödberg, Tommy I.; Straussberg, Rachel; Swoboda, Kathryn J.; Suri, Mohnish; Tacke, Uta; Tan, Tiong Y.; Naude, Johann te Water; Teik, Keng Wee; Thomas, Maya Mary; Till, Marianne; Tonduti, Davide; Valente, Enza Maria; Van Coster, Rudy Noel; van der Knaap, Marjo S.; Vassallo, Grace; Vijzelaar, Raymon; Vogt, Julie; Wallace, Geoffrey B.; Wassmer, Evangeline; Webb, Hannah J.; Whitehouse, William P.; Whitney, Robyn N.; Zaki, Maha S.; Zuberi, Sameer M.; Livingston, John H.; Rozenberg, Flore; Lebon, Pierre; Vanderver, Adeline; Orcesi, Simona; Rice, Gillian I.

    2015-01-01

    Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome

  16. NR2A- and NR2B-Containing NMDA Receptors in the Prelimbic Medial Prefrontal Cortex Differentially Mediate Trace, Delay, and Contextual Fear Conditioning

    ERIC Educational Resources Information Center

    Gilmartin, Marieke R.; Kwapis, Janine L.; Helmstetter, Fred J.

    2013-01-01

    Activation of "N"-methyl-D-aspartate receptors (NMDAR) in the prelimbic medial prefrontal cortex (PL mPFC) is necessary for the acquisition of both trace and contextual fear memories, but it is not known how specific NR2 subunits support each association. The NR2B subunit confers unique properties to the NMDAR and may differentially…

  17. Ligand-dependent serum response factor activation by the human CC chemokine receptors CCR2a and CCR2b is mediated by G proteins of the Gq family.

    PubMed

    Vatter, Petra; Schuhholz, Julia; Koenig, Carolin; Pfreimer, Mariana; Moepps, Barbara

    2016-06-01

    Expression of the human CCR2 receptors, CCR2a and CCR2b, in mammalian cells results in ligand-dependent changes in the activity of multiple cellular signal transduction pathways, mediated in most cases by pertussis toxin-sensitive heterotrimeric G proteins of the Gi/o subfamily. In addition, CCR2a and CCR2b receptors have been shown to couple to Gq family members, triggering the canonical activation of phospholipase Cβ isoenzymes. Activation of pertussis toxin-insensitive Gq proteins by cell-surface receptors is not only coupled to activation of phospholipase isoenzymes but also to Rho guanine nucleotide exchange factors, which in turn mediate activation of the Rho GTPases. Activated Rho GTPases regulate numerous cellular functions, including the organization of the actin cytoskeleton and gene transcription, such as the transcription factor serum response factor. These findings prompted us to investigate whether CCR2a and/or CCR2b stimulate serum response factor activity. The results presented herein demonstrate that stimulation of human CCR2a- or CCR2b-expressing COS-7 cells caused a vigorous induction of serum response factor activity. This effect was specifically mediated by Gq and/or G14, as well as Rho A and/or a closely related Rho GTPase. Furthermore, the stimulatory effect of CCR2a and CCR2b and Gαq was sensitive to coexpression of the Gαq-interacting leukemia-associated Rho guanine nucleotide exchange factor. The findings of the work indicate a role for Gαq and/or Gα14 and in CCR2a/CCR2b-stimulated Rho A GTPase-mediated serum response factor activation and introduce a noncanonical pathway activated by CCR2 receptors by coupling to Gq proteins. PMID:26823487

  18. Achievement of sustained viral response after switching treatment from pegylated interferon α-2b to α-2a and ribavirin in patients with recurrence of hepatitis C virus genotype 1 infection after liver transplantation: a case report.

    PubMed

    Kawaoka, Tomokazu; Hiraga, Nobuhiko; Takahashi, Shoichi; Takaki, Shintaro; Tsuge, Masataka; Nagaoki, Yuko; Hashimoto, Yoshimasa; Katamura, Yoshio; Miki, Daiki; Hiramatsu, Akira; Waki, Koji; Imamura, Michio; Kawakami, Yoshiiku; Aikata, Hiroshi; Ochi, Hidenori; Tashiro, Hirotaka; Ohdan, Hideki; Chayama, Kazuaki

    2012-01-01

    We report a case in which sustained viral response was achieved after switching treatment from pegylated interferon (PEG-IFN) α-2b to α-2a and ribavirin (RBV) in patients with recurrence of hepatitis C virus (HCV) infection after living donor liver transplantation. The patient was a 62-year-old man with liver cirrhosis due to HCV genotype 1b infection. The patient had 8 amino acid (aa) substitutions in the interferon sensitivity-determining region, and had substitutions for mutant and wild-type at aa70 and aa91, respectively, in the core region. The patient had minor genotype (GG) IL28B single nucleotide polymorphisms (rs8099917). He had initially received interferon α-2b and RBV for 2 years, and later developed hepatocellular carcinoma (HCC). After surgical resection of HCC, he subsequently received PEG-IFN α-2b and RBV for 1.5 years, without undetectable viremia during the treatment course. Due to recurrence of HCC, the patient received a living donor liver transplantation. Later on, hepatitis C relapsed. For the management of relapse, he received another course of PEG-IFN α-2b and RBV. However, breakthrough viremia occurred. PEG-IFN was thus switched from α-2b to α-2a and RBV for another 17 months. The patient eventually achieved a sustained viral response. PMID:21865660

  19. Both NR2A and NR2B Subunits of the NMDA Receptor Are Critical for Long-Term Potentiation and Long-Term Depression in the Lateral Amygdala of Horizontal Slices of Adult Mice

    ERIC Educational Resources Information Center

    Muller, Tobias; Albrecht, Doris; Gebhardt, Christine

    2009-01-01

    The lateral nucleus of the amygdala (LA) is implicated in emotional and social behaviors. We recently showed that in horizontal brain slices, activation of NMDA receptors (NMDARs) is a requirement for persistent synaptic alterations in the LA, such as long-term potentiation (LTP) and long-term depression (LTD). In the LA, NR2A- and NR2B-type NMDRs…

  20. Amygdala Infusions of an NR2B-Selective or an NR2A-Preferring NMDA Receptor Antagonist Differentially Influence Fear Conditioning and Expression in the Fear-Potentiated Startle Test

    ERIC Educational Resources Information Center

    Walker, David L.; Davis, Michael

    2008-01-01

    Within the amygdala, most N-methyl-D-aspartic acid (NMDA) receptors consist of NR1 subunits in combination with either NR2A or NR2B subunits. Because the particular subunit composition greatly influences the receptors' properties, we investigated the contribution of both subtypes to fear conditioning and expression. To do so, we infused the…

  1. Effect of porcine circovirus type 2a or 2b on infection kinetics and pathogenicity of two genetically divergent strains of porcine reproductive and respiratory syndrome virus in the conventional pig model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to characterize the infection dynamics and pathogenicity of two heterologous type 2 porcine reproductive and respiratory syndrome virus (PRRSV) isolates in a conventional pig model under the influence of concurrent porcine circovirus (PCV) subtype 2a or 2b infection. ...

  2. Figure Drawing

    ERIC Educational Resources Information Center

    Herberholz, Barbara

    2010-01-01

    The figure has "figured" prominently in the choice of subject matter for many artists throughout history. Whether they may choose to depict it in an abstract or expressive form, most artists are quite capable of realistic portrayals of the human form. And all people know that one of the very first drawings made by young children is a symbol for…

  3. Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein

    PubMed Central

    Liaw, Wen-Jinn; Zhu, Xu-Guang; Yaster, Myron; Johns, Roger A; Gauda, Estelle B; Tao, Yuan-Xiang

    2008-01-01

    Postsynaptic density (PSD)-93, a neuronal scaffolding protein, binds to and clusters N-methyl-D-aspartate receptor (NMDAR) subunits NR2A and NR2B at cellular membranes in vitro. However, the roles of PSD-93 in synaptic NR2A and NR2B targeting in the central nervous system and NMDAR-dependent physiologic and pathologic processes are still unclear. We report here that PSD-93 deficiency significantly decreased the amount of NR2A and NR2B in the synaptosomal membrane fractions derived from spinal cord dorsal horn and forebrain cortex but did not change their levels in the total soluble fraction from either region. However, PSD-93 deficiency did not markedly change the amounts of NR2A and NR2B in either synaptosomal or total soluble fractions from cerebellum. In mice deficient in PSD-93, morphine dose-dependent curve failed to shift significantly rightward as it did in wild type (WT) mice after acute and chronic morphine challenge. Unlike WT mice, PSD-93 knockout mice also showed marked losses of NMDAR-dependent morphine analgesic tolerance and associated abnormal sensitivity in response to mechanical, noxious thermal, and formalin-induced inflammatory stimuli after repeated morphine injection. In addition, PSD-93 knockout mice displayed dramatic loss of jumping activity, a typical NMDAR-mediated morphine withdrawal abstinence behavior. These findings indicate that impaired NMDAR-dependent neuronal plasticity following repeated morphine injection in PSD-93 knockout mice is attributed to PSD-93 deletion-induced alterations of synaptic NR2A and NR2B expression in dorsal horn and forebrain cortex neurons. The selective effect of PSD-93 deletion on synaptic NMDAR expression in these two major pain-related regions might provide the better strategies for the prevention and treatment of opioid tolerance and physical dependence. PMID:18851757

  4. Efficacy, Safety, and Dose of Pafuramidine, a New Oral Drug for Treatment of First Stage Sleeping Sickness, in a Phase 2a Clinical Study and Phase 2b Randomized Clinical Studies

    PubMed Central

    Burri, Christian; Yeramian, Patrick D.; Merolle, Ada; Serge, Kazadi Kyanza; Mpanya, Alain; Lutumba, Pascal; Mesu, Victor Kande Betu Ku; Lubaki, Jean-Pierre Fina; Mpoto, Alfred Mpoo; Thompson, Mark; Munungu, Blaise Fungula; Josenando, Théophilo; Bernhard, Sonja C.; Olson, Carol A.; Blum, Johannes; Tidwell, Richard R.; Pohlig, Gabriele

    2016-01-01

    Background Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT. Methods The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent. Findings/Conclusion Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3. PMID:26881924

  5. (1R, 3S)-(−)-Trans-PAT: A novel full-efficacy serotonin 5-HT2C receptor agonist with 5-HT2A and 5-HT2B receptor inverse agonist/antagonist activity

    PubMed Central

    Booth, Raymond G.; Fang, Lijuan; Huang, Yingsu; Wilczynski, Andrzej; Sivendran, Sashikala

    2009-01-01

    The serotonin 5-HT2A, 5-HT2B, and 5-HT2C G protein-coupled receptors signal primarily through Gαq to activate phospholipase C (PLC) and formation of inositol phosphates (IP) and diacylglycerol. The human 5-HT2C receptor, expressed exclusively in the central nervous system, is involved in several physiological and psychological processes. Development of 5-HT2C agonists that do not also activate 5-HT2A or 5-HT2B receptors is challenging because transmembrane domain identity is about 75% among 5-HT2 subtypes. This paper reports 5-HT2 receptor affinity and function of (1R,3S)-(−)-trans-1-phenyl-3-dimethylamino-1,2,3,4-tetrahydronaphthalene (PAT), a small molecule that produces anorexia and weight-loss after peripheral administration to mice. (−)-Trans-PAT is a stereoselective full-efficacy agonist at human 5-HT2C receptors, plus, it is a 5-HT2A/5-HT2B inverse agonist and competitive antagonist. The Ki of (−)-trans-PAT at 5-HT2A, 5-HT2B, and 5-HT2C receptors is 410, 1200, and 37 nM, respectively. Functional studies measured activation of PLC/[3H]-IP formation in clonal cells expressing human 5-HT2 receptors. At 5-HT2C receptors, (−)-trans-PAT is an agonist (EC50 = 20 nM) comparable to serotonin in potency and efficacy. At 5-HT2A and 5-HT2B receptors, (−)-trans-PAT is an inverse agonist (IC50 = 490 and 1,000 nM, respectively) and competitive antagonist (KB = 460 and 1400 nM, respectively) of serotonin. Experimental results are interpreted in light of molecular modeling studies indicating the (−)-trans-PAT protonated amine can form an ionic bond with D3.32 of 5-HT2A and 5-HT2C receptors, but, not with 5-HT2B receptors. In addition to probing 5-HT2 receptor structure and function, (−)-trans-PAT is a novel lead regarding 5-HT2C agonist/5-HT2A inverse agonist drug development for obesity and neuropsychiatric disorders. PMID:19397907

  6. Determination of O2(a1 delta g) and O2(b1 sigma+ g) yields in the reaction O + ClO --> Cl + O2: implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, M. T.; Yung, Y. L.

    1987-01-01

    A discharge flow apparatus with chemiluminescence detector has been used to study the reaction O + ClO --> Cl + O2, where O2 = O2(a1 delta g) or O2(b1 sigma+ g). The measured quantum yields for producing O2(a1 delta g) and O2(b1 sigma+ g) in the above reaction are less than 2.5 x 10(-2) and equal to (4.4 +/- 1.1) x 10(-4), respectively. The observed O2(a1 delta g) airglow of Venus cannot be explained in the context of standard photochemistry using our experimental results and those reported in recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the mesosphere of Venus is suggested.

  7. Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China

    PubMed Central

    Geng, Yufei; Guo, Donghua; Li, Chunqiu; Wang, Enyu; Wei, Shan; Wang, Zhihui; Yao, Shuang; Zhao, Xiwen; Su, Mingjun; Wang, Xinyu; Wang, Jianfa; Wu, Rui; Feng, Li; Sun, Dongbo

    2015-01-01

    To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%–100% nucleotide identity and 97.6%–100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains. PMID:26348721

  8. Co-Circulation of the Rare CPV-2c with Unique Gln370Arg Substitution, New CPV-2b with Unique Thr440Ala Substitution, and New CPV-2a with High Prevalence and Variation in Heilongjiang Province, Northeast China.

    PubMed

    Geng, Yufei; Guo, Donghua; Li, Chunqiu; Wang, Enyu; Wei, Shan; Wang, Zhihui; Yao, Shuang; Zhao, Xiwen; Su, Mingjun; Wang, Xinyu; Wang, Jianfa; Wu, Rui; Feng, Li; Sun, Dongbo

    2015-01-01

    To trace evolution of canine parvovirus-2 (CPV-2), a total of 201 stool samples were collected from dogs with diarrhea in Heilongjiang province of northeast China from May 2014 to April 2015. The presence of CPV-2 in the samples was determined by PCR amplification of the VP2 gene (568 bp) of CPV-2. The results revealed that 95 samples (47.26%) were positive for CPV-2, and they showed 98.8%-100% nucleotide identity and 97.6%-100% amino acid identity. Of 95 CPV-2-positive samples, types new2a (Ser297Ala), new2b (Ser297Ala), and 2c accounted for 64.21%, 21.05%, and 14.74%, respectively. The positive rate of CPV-2 and the distribution of the new2a, new2b and 2c types exhibited differences among regions, seasons, and ages. Immunized dogs accounted for 48.42% of 95 CPV-2-positive samples. Coinfections with canine coronavirus, canine kobuvirus, and canine bocavirus were identified. Phylogenetic analysis revealed that the identified new2a, new2b, and CPV-2c strains in our study exhibited a close relationship with most of the CPV-2 strains from China; type new2a strains exhibited high variability, forming three subgroups; type new2b and CPV-2c strains formed one group with reference strains from China. Of 95 CPV-2 strains, Tyr324Ile and Thr440Ala substitutions accounted for 100% and 64.21%, respectively; all type new2b strains exhibited the Thr440Ala substitution, while the unique Gln370Arg substitution was found in all type 2c strains. Recombination analysis using entire VP2 gene indicated possible recombination events between the identified CPV-2 strains and reference strains from China. Our data revealed the co-circulation of new CPV-2a, new CPV-2b, and rare CPV-2c, as well as potential recombination events among Chinese CPV-2 strains. PMID:26348721

  9. Meperidine, remifentanil and tramadol but not sufentanil interact with alpha(2)-adrenoceptors in alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor knock out mice brain.

    PubMed

    Höcker, Jan; Weber, Bernd; Tonner, Peter H; Scholz, Jens; Brand, Philipp-Alexander; Ohnesorge, Henning; Bein, Berthold

    2008-03-17

    alpha(2)-adrenoceptor agonists like clonidine or dexmedetomidine increase the sedative and analgesic actions of opioids. Furthermore opioids like meperidine show potent anti-shivering effects like alpha(2)-adrenoceptor agonists. The underlying molecular mechanisms of these effects are still poorly defined. The authors therefore studied the ability of four different opioids (meperidine, remifentanil, sufentanil and tramadol) to interact with different alpha(2)-adrenoceptor subtypes in mice lacking individual alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptors (alpha(2)-adrenoceptor knock out (alpha(2)-AR KO) mice)). The interaction of opioids with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]-paraiodoclonidine ([(125)I]-PIC) from alpha(2)-adrenoceptors in different brain regions by increasing opioid concentrations was measured, and binding affinity of the analysed opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified. Meperidine, remifentanil and tramadol but not sufentanil provoked dose dependent displacement of specifically bound [(125)I]-PIC from all alpha(2)-adrenoceptor subtypes in cortex, cerebellum, medulla oblongata, thalamus, hippocampus and pons. Required concentrations of meperidine and remifentanil for [(125)I]-PIC displacement from alpha(2B)- and alpha(2C)-adrenoceptors were lower than from alpha(2A)-adrenoceptors, indicating higher binding affinity for alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, [(125)I]-PIC displacement by tramadol indicated higher binding affinity to alpha(2A)-adrenoceptors than to alpha(2B)- and alpha(2C)-adrenoceptors. Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C

  10. Albumin Stimulates the Activity of the Human UDP-Glucuronosyltransferases 1A7, 1A8, 1A10, 2A1 and 2B15, but the Effects Are Enzyme and Substrate Dependent

    PubMed Central

    Svaluto-Moreolo, Paolo; Dziedzic, Klaudyna; Yli-Kauhaluoma, Jari; Finel, Moshe

    2013-01-01

    Human UDP-glucuronosyltransferases (UGTs) are important enzymes in metabolic elimination of endo- and xenobiotics. It was recently shown that addition of fatty acid free bovine serum albumin (BSA) significantly enhances in vitro activities of UGTs, a limiting factor in in vitro–in vivo extrapolation. Nevertheless, since only few human UGT enzymes were tested for this phenomenon, we have now performed detailed enzyme kinetic analysis on the BSA effects in six previously untested UGTs, using 2–4 suitable substrates for each enzyme. We also examined some of the previously tested UGTs, but using additional substrates and a lower BSA concentration, only 0.1%. The latter concentration allows the use of important but more lipophilic substrates, such as estradiol and 17-epiestradiol. In five newly tested UGTs, 1A7, 1A8, 1A10, 2A1, and 2B15, the addition of BSA enhanced, to a different degree, the in vitro activity by either decreasing reaction’s Km, increasing its Vmax, or both. In contrast, the activities of UGT2B17, another previously untested enzyme, were almost unaffected. The results of the assays with the previously tested UGTs, 1A1, 1A6, 2B4, and 2B7, were similar to the published BSA only as far as the BSA effects on the reactions’ Km are concerned. In the cases of Vmax values, however, our results differ significantly from the previously published ones, at least with some of the substrates. Hence, the magnitude of the BSA effects appears to be substrate dependent, especially with respect to Vmax increases. Additionally, the BSA effects may be UGT subfamily dependent since Km decreases were observed in members of subfamilies 1A, 2A and 2B, whereas large Vmax increases were only found in several UGT1A members. The results shed new light on the complexity of the BSA effects on the activity and enzyme kinetics of the human UGTs. PMID:23372764

  11. Alterations of the tumor suppressor genes CDKN2A (p16(INK4a)), p14(ARF), CDKN2B (p15(INK4b)), and CDKN2C (p18(INK4c)) in atypical and anaplastic meningiomas.

    PubMed

    Boström, J; Meyer-Puttlitz, B; Wolter, M; Blaschke, B; Weber, R G; Lichter, P; Ichimura, K; Collins, V P; Reifenberger, G

    2001-08-01

    We investigated 67 meningothelial tumors (20 benign meningiomas, 34 atypical meningiomas, and 13 anaplastic meningiomas) for losses of genetic information from chromosome arms 1p and 9p, as well as for deletion, mutation, and expression of the tumor suppressor genes CDKN2A (p16(INKa)/MTS1), p14(ARF), CDKN2B (p15(INK4b)/MTS2) (all located at 9p21) and CDKN2C (1p32). Comparative genomic hybridization and microsatellite analysis showed losses on 1p in 11 anaplastic meningiomas (85%), 23 atypical meningiomas (68%), and 5 benign meningiomas (25%). One atypical meningioma with loss of heterozygosity on 1p carried a somatic CDKN2C mutation (c.202C>T: R68X). Losses on 9p were found in five anaplastic meningiomas (38%), six atypical meningiomas (18%), and one benign meningioma (5%). Six anaplastic meningiomas (46%) and one atypical meningioma (3%) showed homozygous deletions of the CDKN2A, p14(ARF), and CDKN2B genes. Two anaplastic meningiomas carried somatic point mutations in CDKN2A (c.262G>T: E88X and c.262G>A: E88K) and p14(ARF) (c.305G>T: G102V and c.305G>A: G102E). One anaplastic meningioma, three atypical meningiomas, and one benign meningioma without a demonstrated homozygous deletion or mutation of CDKN2A, p14(ARF), or CDKN2B lacked detectable transcripts from at least one of these genes. Hypermethylation of CDKN2A, p14(ARF), and CDKN2B could be demonstrated in one of these cases. Taken together, our results indicate that CDKN2C is rarely altered in meningiomas. However, the majority of anaplastic meningiomas either show homozygous deletions of CDKN2A, p14(ARF), and CDKN2B, mutations in CDKN2A and p14(ARF), or lack of expression of one or more of these genes. Thus, inactivation of the G(1)/S-phase cell-cycle checkpoint is an important aberration in anaplastic meningiomas. PMID:11485924

  12. Chronic brain inflammation causes a reduction in GluN2A and GluN2B subunits of NMDA receptors and an increase in the phosphorylation of mitogen-activated protein kinases in the hippocampus

    PubMed Central

    2014-01-01

    Neuroinflammation plays a key role in the initiation and progression of neurodegeneration in Alzheimer’s disease (AD). Chronic neuroinflammation results in diminished synaptic plasticity and loss of GluN1 N-methyl-D-aspartate (NMDA) receptors in the hippocampus, leading to the cognitive deficits that are the most common symptoms of AD. Therefore, it is suggested that chronic inflammation may alter expression levels of GluN2A and GluN2B subunits of NMDA receptors and associated intracellular signalling. Chronic neuroinflammation was induced by chronic infusion of lipopolysaccharide (LPS) into the fourth ventricle in Fischer-344 rats. The status of hippocampus-dependent memory was evaluated in control rats and rats chronically infused with LPS. Microglial activation in the hippocampus was examined using immunohistochemical staining. Western blot analysis was used to measure membrane levels of GluN2A and GluN2B subunits of NMDA receptors and mitogen-activated protein kinase (MAPK) in the hippocampi of these rats, and immunofluorescent double labeling was used to assess the cellular location of MAPK. Microglial activation was observed in the hippocampi of rats that showed memory impairments with chronic LPS infusion. Chronic LPS infusion reduced the levels of GluN2A and GluN2B and increased the levels of phosphorylated MAPKs in the hippocampus. MAPK-positive immunoreactivity was observed mostly in the neurons and also in non-neuronal cells. Reductions in GluN2A and GluN2B subunits of NMDA receptors coupled with altered MAPK signaling, in response to inflammatory stimuli may be related to the cognitive deficits observed in AD. PMID:24761931

  13. The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis

    PubMed Central

    Üner, Aykut; Gonçalves, Gabriel H.M.; Li, Wenjing; Porceban, Matheus; Caron, Nicole; Schönke, Milena; Delpire, Eric; Sakimura, Kenji; Bjørbæk, Christian

    2015-01-01

    Objective Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight homeostasis. NMDARs typically consist of the obligatory GluN1 subunit and different GluN2 subunits, the latter exerting crucial differential effects on channel activity and neuronal function. Currently, the role of specific GluN2 subunits in AgRP and POMC neurons on whole body energy and glucose balance is unknown. Methods We used the cre-lox system to genetically delete GluN2A or GluN2B only from AgRP or POMC neurons in mice. Mice were then subjected to metabolic analyses and assessment of AgRP and POMC neuronal function through morphological studies. Results We show that loss of GluN2B from AgRP neurons reduces body weight, fat mass, and food intake, whereas GluN2B in POMC neurons is not required for normal energy balance control. GluN2A subunits in either AgRP or POMC neurons are not required for regulation of body weight. Deletion of GluN2B reduces the number of AgRP neurons and decreases their dendritic length. In addition, loss of GluN2B in AgRP neurons of the morbidly obese and severely diabetic leptin-deficient Lepob/ob mice does not affect body weight and food intake but, remarkably, leads to full correction of hyperglycemia. Lepob/ob mice lacking GluN2B in AgRP neurons are also more sensitive to leptin's anti-obesity actions. Conclusions GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action. PMID:26500840

  14. Preliminary Investigation of the Contribution of CYP2A6, CYP2B6, and UGT1A9 Polymorphisms on Artesunate-Mefloquine Treatment Response in Burmese Patients with Plasmodium falciparum Malaria

    PubMed Central

    Phompradit, Papichaya; Muhamad, Poonuch; Cheoymang, Anurak; Na-Bangchang, Kesara

    2014-01-01

    CYP2A6, CYP2B6, and UGT1A9 genetic polymorphisms and treatment response after a three-day course of artesunate-mefloquine was investigated in 71 Burmese patients with uncomplicated Plasmodium falciparum malaria. Results provide evidence for the possible link between CYP2A6 and CYP2B6 polymorphisms and plasma concentrations of artesunate/dihydroartemisinin and treatment response. In one patient who had the CYP2A6*1A/*4C genotype (decreased enzyme activity), plasma concentration of artesunate at one hour appeared to be higher, and the concentration of dihydroartemisinin was lower than for those carrying other genotypes (415 versus 320 ng/mL). The proportion of patients with adequate clinical and parasitologic response who had the CYP2B6*9/*9 genotype (mutant genotype) was significantly lower compared with those with late parasitologic failure (14.0% versus 19.0%). Confirmation through a larger study in various malaria-endemic areas is required before a definite conclusion on the role of genetic polymorphisms of these drug-metabolizing enzymes on treatment response after artesunate-based combination therapy can be made. PMID:24891466

  15. CT Scans of NASA BSTRA Balls 5f5, f2, f3, sr2c, nb2a, hb2b

    SciTech Connect

    Gross, J; Thompson, R; Perry, R; Schneberk, D

    2004-01-29

    At the request of Jose Hernandez we performed some feasibility DR/CT scanning of BSTRA Balls of different sizes. To this point we have scanned all the specimens on a single system, HECAT. This particular system employs a 9 meV LINAC as the x-ray source and a THALES 12 x 16 inch 14-bit Amorphous Silicon panel as the detector. In this report we describe the system, detail some of its properties, describe the scans performed and present the data. Figure 1 contains a couple of images of the system as fielded in the 9 MeV bay. The LINAC is in the right portion of the picture. The black panels in the blue frame constitute the High Energy collimator developed specifically for High Energy DR/CT scanning (known here as Stonehenge II). The holes in the collimator panels are beveled to match the distribution of the x-rays from the LINAC, and are sized to just subtend the active area of the THALES Amorphous Silicon panel. Consequently the source to detector distance is restricted to a few positions. Nominally our source to detector distance is 6 meters. The part manipulator, part holder fixturing consists of a translate-rotate assembly on a NEWPORT air bearing table. The stages are NEWPORT RV160PP for rotation and NEWPORT IMS400CC for translation. Both are interfaced through an ESP7000 controller, which is connected to our data acquisition computer over USB. The detector holder also resides on this table and includes pitch, roll and yaw adjustments for aligning the panel to the plane of the rotational table and the x-ray beam. The relatively large source to detector distance and LINAC properties (1 mm spot size) conspire to recommend rotation-only scanning. We use a VARIAN LINATRON 3000 with the small spot retrofit implemented. We have measured the source spot size at about 1 mm. Pixel size on the THALES panel is 0.127 um. Consequently we are in a low-cone angle scanning regime which enables rotation-only 3D CT scanning of objects and assemblies with little ''cone

  16. Determination of O2(a1Delta g) and O2(b1Sigma + g) yields in the reaction O + ClO yields Cl + O2 - Implications for photochemistry in the atmosphere of Venus

    NASA Technical Reports Server (NTRS)

    Leu, Ming-Taun; Yung, Yuk L.

    1987-01-01

    A discharge flow apparatus with a chemiluminescence detector was used to investigate the reaction O + ClO yields Cl + O2(asterisk), where O2(asterisk) = O2(a1Delta g) or O2(b1Sigma + g). It is found that the observed O2(a1Delta g) airglow of Venus cannot be explained in the framework of standard photochemistry using the experimental results obtained here and those reported in the recent literature. The possibility of an alternative source of O atoms derived from SO2 photolysis in the Venus mesosphere is suggested.

  17. Go Figure.

    ERIC Educational Resources Information Center

    Greenman, Geri

    2000-01-01

    Describes the first assignment for an intermediate oil painting class in which the students painted the human figure. Explains that the assignment involved three techniques: (1) abstract application of acrylic paint; (2) oil "Paintstiks" from Shiva; and (3) a final layer of actual oil paint. (CMK)

  18. Adenosine A(1), A(2a), A(2b), and A(3) receptors in hematopoiesis. 2. Expression of receptor mRNA in resting and lipopolysaccharide-activated mouse RAW 264.7 macrophages.

    PubMed

    Streitová, D; Hofer, M; Holá, J; Vacek, A; Pospísil, M

    2010-01-01

    Expression of mRNA for adenosine receptor subtypes A(1), A(2a), A(2b), and A(3) in normal and lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages has been investigated using the method of quantitative real-time polymerase chain reaction. The results have shown a very low, unquantifiable expression of adenosine A(1) receptor mRNA in both normal and LPS-activated macrophages. The other three adenosine receptor mRNAs have been found to be expressed at various but always quantifiable levels. Activation of the macrophages by LPS induced upregulation of the expression of adenosine receptor A(2a) and A(2b) mRNA, whereas the expression of adenosine receptor A(3) mRNA was downregulated. Unstimulated macrophages exhibited a high expression of the A(2b) adenosine receptor mRNA. The findings are discussed from the point of view of the antiinflammatory and hematopoiesis-stimulating roles of the adenosine receptor signaling. PMID:19249906

  19. [3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and alpha2C-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and yohimbine.

    PubMed

    Uhlén, S; Dambrova, M; Näsman, J; Schiöth, H B; Gu, Y; Wikberg-Matsson, A; Wikberg, J E

    1998-02-01

    The Kd values of the recently introduced radioligand [3H]RS79948-197 ((8a R,12aS,13a-S)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-metho xy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the recombinant human and rat alpha2A-, alpha2B- and alpha2C- as well as guinea pig alpha2B- and alpha2c-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In addition, the Kd values were also determined for [3H]RS79948-197 for the guinea pig spleen alpha2A-adrenoceptor and for pig alpha2A-, alpha2B- and alpha2C-adrenoceptors in membranes obtained from kidney and striatum. Available radioligands for alpha2-adrenoceptors, besides [3H]RS79948-197 are the tritiated forms of MK912 ((2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octa hydro-2H-benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy-idazoxan), rauwolscine and yohimbine. In the present article the binding constants of all these substances for the alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all species tested MK912 was alpha2C-selective, RX821002 showed a minor alpha2A-selectivity, whereas [3H]RS79948-197 was non-selective among the alpha2-adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine and yohimbine showed relatively low affinities for nmost of the alpha2-adrenoceptor subtypes investigated, the exception being rauwolscine having high affinity for the human and porcine alpha2C-adrenoceptors. PMID:9551719

  20. Cost-effectiveness analysis of treatment with peginterferon-alfa-2a versus peginterferon-alfa-2b for patients with chronic hepatitis C under the public payer perspective in Brazil

    PubMed Central

    2013-01-01

    Background Chronic hepatitis C affects approximately 170 million people worldwide, and thus being one of the main causes of chronic liver disease. About 20% of patients with chronic hepatitis C will develop cirrhosis over 20 years, and present an increased risk of developing hepatic complications. Sustained virological response (SVR) is associated with a better prognosis compared to untreated patients and treatment failures. The objective of this analysis was to compare treatment costs and outcomes of pegylated interferon-alfa-2a versus pegylated interferon-alfa-2b, both associated with ribavirin, in the therapeutic scheme of 24 weeks and 48 week for hepatitis C genotypes 2/3 and genotype 1, respectively, under the Brazilian Public Health System (SUS) scenario. Methods To project disease progression, a Markov model was built based on clinical stages of chronic disease. A Delphi panel was conducted to evaluate medical resources related to each stage, followed by costing of related materials, services, procedures and pharmaceutical products. The evaluation was made from a public payer perspective. The source used for costing was government reimbursement procedures list (SAI/SIH–SUS). Drug acquisition costs were obtained from the Brazilian Official Gazette and “Banco de Preços em Saúde” (government official source). It was assumed a mean patient weight of 70 kg. Costs were reported in 2011 Brazilian Reais (US$1 ≈ $Brz1.80). A systematic review followed by a meta-analysis of the 7 identified randomized controlled trials (RCTs) which compared pegylated interferons, was conducted for obtaining relative efficacy of both drugs: for genotype 2/3, mean rate of SVR was 79.2% for peginterferon-alfa-2a and 73.8% for peginterferon-alfa-2b. For genotype 1, SVR mean rate was 42.09% versus 33.44% (peginterferon-alfa-2a and peginterferon-alfa-2b respectively). Time horizon considered was lifetime. Discount rate for costs and outcomes was 5%, according to Brazilian

  1. Behavioural Assessment of the A2a/NR2B Combination in the Unilateral 6-OHDA-Lesioned Rat Model: A New Method to Examine the Therapeutic Potential of Non-Dopaminergic Drugs.

    PubMed

    Michel, Anne; Downey, Patrick; Van Damme, Xavier; De Wolf, Catherine; Schwarting, Rainer; Scheller, Dieter

    2015-01-01

    In Parkinson's disease (PD), dopaminergic therapies are often associated with the development of motor complications. Attention has therefore been focused on the use of non-dopaminergic drugs. This study developed a new behavioural method capable of demonstrating the added value of combining adenosinergic and glutamatergic receptor antagonists in unilateral 6-OHDA lesioned rats. Rats were dosed orally with Tozadenant, a selective A2A receptor antagonist, and three different doses of Radiprodil, an NR2B-selective NMDA receptor antagonist. The drugs were given alone or in combination and rats were placed in an open-field for behavioural monitoring. Video recordings were automatically analysed. Five different behaviours were scored: distance traveled, ipsi- and contraversive turns, body position, and space occupancy. The results show that A2A or NR2B receptor antagonists given alone or in combination did not produce enhanced turning as observed with an active dose of L-Dopa/benserazide. Instead the treated rats maintained a straight body position, were able to shift from one direction to the other and occupied a significantly larger space in the arena. The highest "Tozadenant/Radiprodil" dose combination significantly increased all five behavioural parameters recorded compared to rats treated with vehicle or the same doses of the drugs alone. Our data suggest that the A2A/NR2B antagonist combination may be able to stimulate motor activity to a similar level as that achieved by L-Dopa but in the absence of the side-effects that are associated with dopaminergic hyperstimulation. If these results translate into the clinic, this combination could represent an alternative symptomatic treatment option for PD. PMID:26322641

  2. Efficacy and tolerability of peginterferon alfa-2a or alfa-2b plus ribavirin in the daily routine treatment of patients with chronic hepatitis C in Germany: the PRACTICE study.

    PubMed

    Witthoeft, T; Hueppe, D; John, C; Goelz, J; Heyne, R; Moeller, B; Teuber, G; Wollschlaeger, S; Baumgarten, A; Simon, K-G; Moog, G; Dikopoulos, N; Mauss, S

    2010-07-01

    In randomized clinical trials, treatment with peginterferon plus ribavirin (RBV) results in a sustained virological response (SVR) in around half of hepatitis C virus genotype 1-infected and 80% of genotype 2/3-infected individuals. This study aimed to evaluate efficacy and tolerability of peginterferon alfa-2a plus RBV compared with peginterferon alfa-2b plus RBV for the treatment of chronic hepatitis C in routine clinical practice. The intent-to-treat cohort consisted of 3414 patients treated with either peginterferon alfa-2a plus RBV (Group A) or peginterferon alfa-2b plus RBV (Group B) in 23 centres participating in the large, multicentre, observational PRACTICE study. Collected data included baseline characteristics, treatment regimen, RBV dose and outcome. Rates of early virological response, end of treatment response and SVR were 76.6%, 75.7% and 52.9% in Group A, and 70.2%, 65.6% and 50.5% in Group B, respectively. In patients matched by baseline parameters, 59.9% of patients in Group A and 55.9% in Group B achieved an SVR (P < or = 0.051). In genotype 1-infected patients matched by baseline parameters and cumulative RBV dose, SVR rates were 49.6% and 43.7% for Group A and Group B, respectively (P < or = 0.047); when matched by baseline parameters and RBV starting dose, SVR rates were 49.9% and 44.6%, respectively (P = 0.068). Overall, 21.8% of group A and 29.6% of group B patients discontinued treatment (P < or = 0.0001). The efficacy and tolerability of peginterferon plus RBV in this large cohort of patients treated in routine daily practice was similar to that in randomized clinical trials. In matched pairs analyses, more patients achieved an SVR with peginterferon alfa-2a compared with peginterferon alfa-2b. PMID:20158603

  3. Aquifer-test data for wells H-1, H-2A, H-2B, H-2C, and H-3 at the Waste Isolation Pilot Plant, southeastern New Mexico

    USGS Publications Warehouse

    Huff, G.F.; Gregory, Angela

    2006-01-01

    A series of aquifer tests was performed by the U.S. Geological Survey on geologic units of Permian age at the Waste Isolation Pilot Plant site between February 1979 and July 1980 in wells H-1, H-2 complex (H-2A, H-2B, and H-2C), and H-3. The tested geologic units included the Magenta Dolomite and Culebra Dolomite Members of the Rustler Formation, and the contact zone between the Rustler and Salado Formations. Selected information on the tested formations, test dates, pre-test static water levels, test configurations, and raw data collected during these tests are tabulated in this report.

  4. Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory.

    PubMed

    Milton, Amy L; Merlo, Emiliano; Ratano, Patrizia; Gregory, Ben L; Dumbreck, Jessica K; Everitt, Barry J

    2013-01-16

    Signaling at NMDA receptors (NMDARs) is known to be important for memory reconsolidation, but while most studies show that NMDAR antagonists prevent memory restabilization and produce amnesia, others have shown that GluN2B-selective NMDAR antagonists prevent memory destabilization, protecting the memory. These apparently paradoxical, conflicting data provide an opportunity to define more precisely the requirement for different NMDAR subtypes in the mechanisms underlying memory reconsolidation and to further understand the contribution of glutamatergic signaling to this process. Here, using rats with fully consolidated pavlovian auditory fear memories, we demonstrate a double dissociation in the requirement for GluN2B-containing and GluN2A-containing NMDARs within the basolateral amygdala in the memory destabilization and restabilization processes, respectively. We further show a double dissociation in the mechanisms underlying memory retrieval and memory destabilization, since AMPAR antagonism prevented memory retrieval while still allowing the destabilization process to occur. These data demonstrate that glutamatergic signaling mechanisms within the basolateral amygdala differentially and dissociably mediate the retrieval, destabilization, and restabilization of previously consolidated fear memories. PMID:23325248

  5. Fit 2-B FATHERS.

    ERIC Educational Resources Information Center

    Maiorano, Joseph J.

    2001-01-01

    Fit 2-B FATHERS is a parenting-skills education program for incarcerated adult males. The goals of this program are for participants to have reduced recidivism rates and a reduced risk of their children acquiring criminal records. These goals are accomplished by helping participants become physically, practically, and socially fit for the demands…

  6. Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques.

    PubMed

    El Raziky, Maissa; Fathalah, Waleed Fouad; Zakaria, Zeinab; Eldeen, Hadeel Gamal; Abul-Fotouh, Amr; Salama, Ahmed; Awad, Abubakr; Esmat, Gamal; Mabrouk, Mahasen

    2016-05-01

    Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG-IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree)-based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 × 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG-IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 × 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response. PMID:26859168

  7. Aryne [3 + 2] cycloaddition with N-sulfonylpyridinium imides and in situ generated N-sulfonylisoquinolinium imides: a potential route to pyrido[1,2-b]indazoles and indazolo[3,2-a]isoquinolines.

    PubMed

    Zhao, Jingjing; Li, Pan; Wu, Chunrui; Chen, Hongli; Ai, Wenying; Sun, Renhong; Ren, Hailong; Larock, Richard C; Shi, Feng

    2012-03-01

    The aryne [3 + 2] cycloaddition process with pyridinium imides breaks the aromaticity of the pyridine ring. By equipping the imide nitrogen with a sulfonyl group, the intermediate readily eliminates a sulfinate anion to restore the aromaticity, leading to the formation of pyrido[1,2-b]indazoles. The scope and limitation of this reaction are discussed. As an extension of this chemistry, N-tosylisoquinolinium imides, generated in situ from N'-(2-alkynylbenzylidene)-tosylhydrazides via an AgOTf-catalyzed 6-endo-dig electrophilic cyclization, readily undergo aryne [3 + 2] cycloaddition to afford indazolo[3,2-a]-isoquinolines in the same pot, offering a highly efficient route to these potential anticancer agents. PMID:22278679

  8. Specific role of α2A - and α2B -, but not α2C -, adrenoceptor subtypes in the inhibition of the vasopressor sympathetic out-flow in diabetic pithed rats.

    PubMed

    Altamirano-Espinoza, Alain H; Manrique-Maldonado, Guadalupe; Marichal-Cancino, Bruno A; Villalón, Carlos M

    2015-07-01

    Several lines of evidence have shown an association of diabetes with a catecholamines' aberrant homeostasis involving a drastic change in the expression of adrenoceptors. This homeostatic alteration includes, among other things, atypical actions of α2 -adrenoceptor agonists within central and peripheral α2 -adrenoceptors (e.g. profound antinociceptive effects in diabetic subjects). Hence, this study investigated the pharmacological profile of the α2 -adrenoceptor subtypes that inhibit the vasopressor sympathetic out-flow in streptozotocin-pre-treated (diabetic) pithed rats. For this purpose, B-HT 933 (up to 30 μg/kg min) was used as a selective α2 -adrenoceptor agonist and rauwolscine as a non-selective α2A/2B/2C -adrenoceptor antagonist; in addition, BRL 44408, imiloxan and JP-1302 were used as subtype-selective α2A -, α2B - and α2C -adrenoceptor antagonists, respectively (all given i.v.). I.v. continuous infusions of B-HT 933 inhibited the vasopressor responses induced by electrical sympathetic stimulation without affecting those by i.v. bolus injections of noradrenaline in both normoglycaemic and diabetic rats. Interestingly, the ED50 for B-HT 933 in diabetic rats (25 μg/kg min) was almost 1-log unit greater than that in normoglycaemic rats (3 μg/kg.min). Moreover, the sympatho-inhibition induced by 10 μg/kg min B-HT 933 in diabetic rats was (i) abolished by 300 μg/kg rauwolscine or 100 and 300 μg/kg BRL 44408; (ii) partially blocked by 1000 μg/kg imiloxan; and (iii) unchanged by 1000 μg/kg JP-1302. Our findings, taken together, suggest that B-HT 933 has a less potent inhibitory effect on the sympathetic vasopressor responses in diabetic (compared to normoglycaemic) rats and that can probably be ascribed to a down-regulation of α2C -adrenoceptors. PMID:25407049

  9. A novel aminotetralin-type serotonin (5-HT) 2C receptor-specific agonist and 5-HT2A competitive antagonist/5-HT2B inverse agonist with preclinical efficacy for psychoses.

    PubMed

    Canal, Clinton E; Morgan, Drake; Felsing, Daniel; Kondabolu, Krishnakanth; Rowland, Neil E; Robertson, Kimberly L; Sakhuja, Rajeev; Booth, Raymond G

    2014-05-01

    Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (-)-trans-(2S,4R)-4-(3'[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (-)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (-)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (-)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (-)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (-)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (-)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders. PMID:24563531

  10. A Novel Aminotetralin-Type Serotonin (5-HT) 2C Receptor-Specific Agonist and 5-HT2A Competitive Antagonist/5-HT2B Inverse Agonist with Preclinical Efficacy for Psychoses

    PubMed Central

    Morgan, Drake; Felsing, Daniel; Kondabolu, Krishnakanth; Rowland, Neil E.; Robertson, Kimberly L.; Sakhuja, Rajeev; Booth, Raymond G.

    2014-01-01

    Development of 5-HT2C agonists for treatment of neuropsychiatric disorders, including psychoses, substance abuse, and obesity, has been fraught with difficulties, because the vast majority of reported 5-HT2C selective agonists also activate 5-HT2A and/or 5-HT2B receptors, potentially causing hallucinations and/or cardiac valvulopathy. Herein is described a novel, potent, and efficacious human 5-HT2C receptor agonist, (−)-trans-(2S,4R)-4-(3′[meta]-bromophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (−)-MBP), that is a competitive antagonist and inverse agonist at human 5-HT2A and 5-HT2B receptors, respectively. (−)-MBP has efficacy comparable to the prototypical second-generation antipsychotic drug clozapine in three C57Bl/6 mouse models of drug-induced psychoses: the head-twitch response elicited by [2,5]-dimethoxy-4-iodoamphetamine; hyperlocomotion induced by MK-801 [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (dizocilpine maleate)]; and hyperlocomotion induced by amphetamine. (−)-MBP, however, does not alter locomotion when administered alone, distinguishing it from clozapine, which suppresses locomotion. Finally, consumption of highly palatable food by mice was not increased by (−)-MBP at a dose that produced at least 50% maximal efficacy in the psychoses models. Compared with (−)-MBP, the enantiomer (+)-MBP was much less active across in vitro affinity and functional assays using mouse and human receptors and also translated in vivo with comparably lower potency and efficacy. Results indicate a 5-HT2C receptor-specific agonist, such as (−)-MBP, may be pharmacotherapeutic for psychoses, without liability for obesity, hallucinations, heart disease, sedation, or motoric disorders. PMID:24563531

  11. Boeing XF2B-1 (F2B-1)

    NASA Technical Reports Server (NTRS)

    1931-01-01

    Boeing XF2B-1 (F2B-1): Serving as the prototype for the F2B-1 shipboard fighter, the XF2B-1 differed visually in having a pointed spinner and an unbalanced rudder. Like many aircraft of its day, the Boeing model 69 was powered by a Pratt & Whitney Wasp radial engine.

  12. Case-control association study of polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B and epilepsy.

    PubMed

    Baum, Larry; Haerian, Batoul Sadat; Ng, Ho-Keung; Wong, Virginia C N; Ng, Ping Wing; Lui, Colin H T; Sin, Ngai Chuen; Zhang, Chunbo; Tomlinson, Brian; Wong, Gary Wing-Kin; Tan, Hui Jan; Raymond, Azman Ali; Mohamed, Zahurin; Kwan, Patrick

    2014-05-01

    High-frequency action potentials are mediated by voltage-gated sodium channels, composed of one large α subunit and two small β subunits, encoded mainly by SCN1A, SCN2A, SCN3A, SCN1B, and SCN2B genes in the brain. These play a key role in epilepsy, with the most commonly mutated gene in epilepsy being SCN1A. We examined whether polymorphisms in the above genes affect epilepsy risk in 1,529 epilepsy patients and 1,935 controls from four ethnicities or locations: Malay, Indian, and Chinese, all from Malaysia, and Chinese from Hong Kong. Of patients, 19 % were idiopathic, 42 % symptomatic, and 40 % cryptogenic. We genotyped 43 polymorphisms: 27 in Hong Kong, 28 in Malaysia, and 12 in both locations. The strongest association with epilepsy was rs3812718, or SCN1A IVS5N+5G>A: odds ratio (OR) = 0.85 for allele G (p = 0.0009) and 0.73 for genotype GG versus AA (p = 0.003). The OR was between 0.76 and 0.87 for all ethnicities. Meta-analysis confirmed the association (OR = 0.81 and p = 0.002 for G, and OR = 0.67 and p = 0.007 for GG versus AA), which appeared particularly strong for Indians and for febrile seizures. Allele G affects splicing and speeds recovery from inactivation. Since SCN1A is preferentially expressed in inhibitory neurons, G may decrease epilepsy risk. SCN1A rs10188577 displayed OR = 1.20 for allele C (p = 0.003); SCN2A rs12467383 had OR = 1.16 for allele A (p = 0.01), and displayed linkage disequilibrium with rs2082366 (r (2) = 0.67), whose genotypes tended toward association with SCN2A brain expression (p = 0.10). SCN1A rs2298771 was associated in Indians (OR = 0.56, p = 0.005) and SCN2B rs602594 with idiopathic epilepsy (OR = 0.62, p = 0.002). Therefore, sodium channel polymorphisms are associated with epilepsy. PMID:24337656

  13. Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

    PubMed

    Dai, Hai-Bin; Xu, Miao-Miao; Lv, Jia; Ji, Xiang-Jun; Zhu, Si-Hai; Ma, Ru-Meng; Miao, Xiao-Lei; Duan, Man-Lin

    2016-09-01

    We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3β in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone. PMID:26350917

  14. SACALC2B

    2007-02-08

    SACALC2B calculates the average solid angle subtended by a rectangular or circular detector window to a coaxial or non-coaxial rectangular, circular or point source, including where the source and detector planes are not parallel. SACALC_CYL calculates the average solid angle subtended by a cylinder to a rectangular or circular source, plane or thick, at any location and orientation. This is needed, for example, in calculating the intrinsic gamma efficiency of a detector such as amore » GM tube. The program also calculates the number of hits on the cylinder side and on each end, and the average path length through the detector volume (assuming no scattering or absorption). Point sources can be modelled by using a circular source of zero radius.« less

  15. Two EPR-detectable [4Fe-4S] clusters, N2a and N2b, are bound to the NuoI (TYKY) subunit of NADH:ubiquinone oxidoreductase (Complex I) from Rhodobacter capsulatus.

    PubMed

    Chevallet, Mireille; Dupuis, Alain; Issartel, Jean-Paul; Lunardi, Joël; van Belzen, Ronald; Albracht, Simon P J

    2003-03-01

    NADH:ubiquinone oxidoreductases (Complex I) contain a subunit, TYKY in the bovine enzyme and NuoI in the enzyme from Rhodobacter capsulatus, which is assumed to bind two [4Fe-4S] clusters because it contains two sets of conserved cysteine motifs similar to those found in the 2[4Fe-4S] ferredoxins. It was recently shown that the TYKY subunit is not an ordinary 2[4Fe-4S] ferredoxin, but has a unique amino acid sequence, which is only found in NAD(P)H:quinone oxidoreductases and certain membrane-bound [NiFe]-hydrogenases expected to be involved in redox-linked proton translocation [FEBS Lett. 485 (2000) 1]. We have generated a set of R. capsulatus mutants in which five out of the eight conserved cysteine residues in NuoI were replaced by other amino acids. The resulting mutants fell into three categories with virtually no, intermediate or quite normal Complex I activities. EPR-spectroscopic analysis of the membranes of the C67S and C106S mutants, two mutants belonging to the second and third group, respectively, showed a specific 50% decrease of the EPR signal attributed to cluster N2. It is concluded that the NuoI (TYKY) subunit binds two clusters N2, called N2a and N2b, which exhibit very similar spectral features when analyzed by X-band EPR spectroscopy. PMID:12615348

  16. Molecular breeding for introgression of fatty acid desaturase mutant alleles (ahFAD2A and ahFAD2B) enhances oil quality in high and low oil containing peanut genotypes.

    PubMed

    Janila, Pasupuleti; Pandey, Manish K; Shasidhar, Yaduru; Variath, Murali T; Sriswathi, Manda; Khera, Pawan; Manohar, Surendra S; Nagesh, Patne; Vishwakarma, Manish K; Mishra, Gyan P; Radhakrishnan, T; Manivannan, N; Dobariya, K L; Vasanthi, R P; Varshney, Rajeev K

    2016-01-01

    High oleate peanuts have two marketable benefits, health benefits to consumers and extended shelf life of peanut products. Two mutant alleles present on linkage group a09 (ahFAD2A) and b09 (ahFAD2B) control composition of three major fatty acids, oleic, linoleic and palmitic acids which together determine peanut oil quality. In conventional breeding, selection for fatty acid composition is delayed to advanced generations. However by using DNA markers, breeders can reject large number of plants in early generations and therefore can optimize time and resources. Here, two approaches of molecular breeding namely marker-assisted backcrossing (MABC) and marker-assisted selection (MAS) were employed to transfer two FAD2 mutant alleles from SunOleic 95R into the genetic background of ICGV 06110, ICGV 06142 and ICGV 06420. In summary, 82 MABC and 387 MAS derived introgression lines (ILs) were developed using DNA markers with elevated oleic acid varying from 62 to 83%. Oleic acid increased by 0.5-1.1 folds, with concomitant reduction of linoleic acid by 0.4-1.0 folds and palmitic acid by 0.1-0.6 folds among ILs compared to recurrent parents. Finally, high oleate ILs, 27 with high oil (53-58%), and 28 ILs with low oil content (42-50%) were selected that may be released for cultivation upon further evaluation. PMID:26566838

  17. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study

    PubMed Central

    Rice, Gillian I; Forte, Gabriella M A; Szynkiewicz, Marcin; Chase, Diana S; Aeby, Alec; Abdel-Hamid, Mohamed S; Ackroyd, Sam; Allcock, Rebecca; Bailey, Kathryn M; Balottin, Umberto; Barnerias, Christine; Bernard, Genevieve; Bodemer, Christine; Botella, Maria P; Cereda, Cristina; Chandler, Kate E; Dabydeen, Lyvia; Dale, Russell C; De Laet, Corinne; De Goede, Christian G E L; del Toro, Mireia; Effat, Laila; Enamorado, Noemi Nunez; Fazzi, Elisa; Gener, Blanca; Haldre, Madli; Lin, Jean-Pierre S-M; Livingston, John H; Lourenco, Charles Marques; Marques, Wilson; Oades, Patrick; Peterson, Pärt; Rasmussen, Magnhild; Roubertie, Agathe; Schmidt, Johanna Loewenstein; Shalev, Stavit A; Simon, Rogelio; Spiegel, Ronen; Swoboda, Kathryn J; Temtamy, Samia A; Vassallo, Grace; Vilain, Catheline N; Vogt, Julie; Wermenbol, Vanessa; Whitehouse, William P; Soler, Doriette; Olivieri, Ivana; Orcesi, Simona; Aglan, Mona S; Zaki, Maha S; Abdel-Salam, Ghada M H; Vanderver, Adeline; Kisand, Kai; Rozenberg, Flore; Lebon, Pierre; Crow, Yanick J

    2015-01-01

    Summary Background Aicardi-Goutières syndrome (AGS) is an inflammatory disorder caused by mutations in any of six genes (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR). The disease is severe and effective treatments are urgently needed. We investigated the status of interferon-related biomarkers in patients with AGS with a view to future use in diagnosis and clinical trials. Methods In this case-control study, samples were collected prospectively from patients with mutation-proven AGS. The expression of six interferon-stimulated genes (ISGs) was measured by quantitative PCR, and the median fold change, when compared with the median of healthy controls, was used to create an interferon score for each patient. Scores higher than the mean of controls plus two SD (>2·466) were designated as positive. Additionally, we collated historical data for interferon activity, measured with a viral cytopathic assay, in CSF and serum from mutation-positive patients with AGS. We also undertook neutralisation assays of interferon activity in serum, and looked for the presence of autoantibodies against a panel of interferon proteins. Findings 74 (90%) of 82 patients had a positive interferon score (median 12·90, IQR 6·14–20·41) compared with two (7%) of 29 controls (median 0·93, IQR 0·57–1·30). Of the eight patients with a negative interferon score, seven had mutations in RNASEH2B (seven [27%] of all 26 patients with mutations in this gene). Repeat sampling in 16 patients was consistent for the presence or absence of an interferon signature on 39 of 41 occasions. Interferon activity (tested in 147 patients) was negatively correlated with age (CSF, r=−0·604; serum, r=−0·289), and was higher in CSF than in serum in 104 of 136 paired samples. Neutralisation assays suggested that measurable antiviral activity was related to interferon α production. We did not record significantly increased concentrations of autoantibodies to interferon subtypes in patients with

  18. The expression profile of acid-sensing ion channel (ASIC) subunits ASIC1a, ASIC1b, ASIC2a, ASIC2b, and ASIC3 in the esophageal vagal afferent nerve subtypes

    PubMed Central

    Dusenkova, Svetlana; Ru, Fei; Surdenikova, Lenka; Nassenstein, Christina; Hatok, Jozef; Dusenka, Robert; Banovcin, Peter; Kliment, Jan; Tatar, Milos

    2014-01-01

    Acid-sensing ion channels (ASICs) have been implicated in esophageal acid sensing and mechanotransduction. However, insufficient knowledge of ASIC subunit expression profile in esophageal afferent nerves hampers the understanding of their role. This knowledge is essential because ASIC subunits form heteromultimeric channels with distinct functional properties. We hypothesized that the esophageal putative nociceptive C-fiber nerves (transient receptor potential vanilloid 1, TRPV1-positive) express multiple ASIC subunits and that the ASIC expression profile differs between the nodose TRPV1-positive subtype developmentally derived from placodes and the jugular TRPV1-positive subtype derived from neural crest. We performed single cell RT-PCR on the vagal afferent neurons retrogradely labeled from the esophagus. In the guinea pig, nearly all (90%–95%) nodose and jugular esophageal TRPV1-positive neurons expressed ASICs, most often in a combination (65–75%). ASIC1, ASIC2, and ASIC3 were expressed in 65–75%, 55–70%, and 70%, respectively, of both nodose and jugular TRPV1-positive neurons. The ASIC1 splice variants ASIC1a and ASIC1b and the ASIC2 splice variant ASIC2b were similarly expressed in both nodose and jugular TRPV1-positive neurons. However, ASIC2a was found exclusively in the nodose neurons. In contrast to guinea pig, ASIC3 was almost absent from the mouse vagal esophageal TRPV1-positive neurons. However, ASIC3 was similarly expressed in the nonnociceptive TRPV1-negative (tension mechanoreceptors) neurons in both species. We conclude that the majority of esophageal vagal nociceptive neurons express multiple ASIC subunits. The placode-derived nodose neurons selectively express ASIC2a, known to substantially reduce acid sensitivity of ASIC heteromultimers. ASIC3 is expressed in the guinea pig but not in the mouse vagal esophageal TRPV1-positive neurons, indicating species differences in ASIC expression. PMID:25190475

  19. Proinflammatory-activated glioma cells induce a switch in microglial polarization and activation status, from a predominant M2b phenotype to a mixture of M1 and M2a/B polarized cells

    PubMed Central

    Lisi, Lucia; Stigliano, Egidio; Lauriola, Libero; Navarra, Pierluigi; Russo, Cinzia Dello

    2014-01-01

    Malignant gliomas are primary brain tumors characterized by morphological and genetic complexities, as well as diffuse infiltration into normal brain parenchyma. Within gliomas, microglia/macrophages represent the largest tumor-infiltrating cell population, contributing by at least one-third to the total tumor mass. Bi-directional interactions between glioma cells and microglia may therefore play an important role on tumor growth and biology. In the present study, we have characterized the influence of glioma-soluble factors on microglial function, comparing the effects of media harvested under basal conditions with those of media obtained after inducing a pro-inflammatory activation state in glioma cells. We found that microglial cells undergo a different pattern of activation depending on the stimulus; in the presence of activated glioma-derived factors, i.e. a condition mimicking the late stage of pathology, microglia presents as a mixture of polarization phenotypes (M1 and M2a/b), with up-regulation of iNOS (inducible nitric oxide synthase), ARG (arginase) and IL (interleukine)-10. At variance, microglia exposed to basal glioma-derived factors, i.e. a condition resembling the early stage of pathology, shows a more specific pattern of activation, with increased M2b polarization status and up-regulation of IL-10 only. As far as viability and cell proliferation are concerned, both LI-CM [LPS (lipopolysaccharide)–IFNγ (interferon γ) conditioned media] and C-CM (control-conditioned media) induce similar effects on microglial morphology. Finally, in human glioma tissue obtained from surgical resection of patients with IV grade glioblastoma, we detected a significant amount of CD68 positive cells, which is a marker of macrophage/microglial phagocytic activity, suggesting that in vitro findings presented here might have a relevance in the human pathology as well. PMID:24689533

  20. All about Lissajous Figures.

    ERIC Educational Resources Information Center

    Greenslade, Thomas B.

    1993-01-01

    Uses diagrams and text to illustrate the use of Lissajous figures (the figures that are traced out when two simple harmonic motions are combined at right angles to each other) in teaching basic physics concepts. Covers the mathematics of the Lissajous Figure; demonstrating Lissajous Figures; and a typical class. (ZWH)

  1. Pancreatic Cancer Stage 2B

    MedlinePlus

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  2. Synthesis and chemistry of the open-cage cobaltaheteroborane cluster [{(η(5)-C5Me5)Co}2B2H2Se2]: a combined experimental and theoretical study.

    PubMed

    Barik, Subrat Kumar; Dorcet, Vincent; Roisnel, Thierry; Halet, Jean-François; Ghosh, Sundargopal

    2015-08-28

    Reaction of [(η(5)-C5Me5)CoCl]2 with a two-fold excess of [LiBH4·thf] followed by heating with an excess of Se powder produces the dicobaltaselenaborane species [{(η(5)-C5Me5)Co}2B2H2Se2], , in good yield. The geometry of resembles a nido pentagonal [Co2B2Se2] bipyramid with a missing equatorial vertex. It can alternatively be seen as an open cage triple-decker cluster. Isolation of permits its reaction with [Fe2(CO)9] to give heterometallic diselenametallaborane [{(η(5)-C5Me5)Co}Fe(CO)3B2H2Se2], . The geometry of is similar to that of with one of the [(η(5)-C5Me5)Co] groups replaced by the isolobal, two-electron fragment [Fe(CO)3]. Both new compounds have been characterized by mass spectrometry, and by (1)H, (11)B and (13)C NMR spectroscopy. The structural architectures have been unequivocally established by crystallographic analysis. In addition, density functional theory calculations were performed to investigate the bonding and electronic properties. The large HOMO-LUMO gaps computed for both clusters are consistent with their thermodynamic stability. Natural bond order calculations predict the absence of metal-metal bonding interaction. PMID:26200318

  3. Telecom 2-B and 2-C (TC2B and TC2C)

    NASA Technical Reports Server (NTRS)

    Dulac, J.; Alvarez, H.

    1991-01-01

    The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

  4. Dynamical study of nonadiabatic unimolecular reactions: The conical intersection between the B-tilde 2B2 and A-tilde 2A1 states of H2O +

    NASA Astrophysics Data System (ADS)

    Dehareng, Dominique; Chapuisat, Xavier; Lorquet, Jean-Claude; Galloy, Claudine; Raseev, Gheorghe

    1983-02-01

    The conical intersection connecting the B˜ 2A' and à 2A' states of the H2O+ ion is studied. The two potential energy surfaces are calculated ab initio by the SCF/CI method within the CS point group. The nonadiabatic coupling matrix elements <Ã‖∂/∂q‖B˜> are computed for several cross sections throughout the potential energy surfaces. A transformation to the diabatic representation is performed. The linear model is found to be a good approximation in the region close to the apex of the cone. The global functions t(s) and T(S) governing the nonadiabatic transition probability are calculated; their shapes are those predicted by the Landau-Zener model (in the Nikitin bidimensional version). A dynamical study is undertaken by means of classical trajectory calculations on the upper adiabatic potential energy surface. An averaged transition probability P¯tr is derived. Excitation of rotation or of the bending mode of H2O before photon impact has no influence on P¯tr. Excitation of the symmetrical or antisymmetrical valence modes of H2O lowers P¯tr. The shape of ln (1-P¯tr) as a function of time indicates the existence of two distinct regimes at short and intermediate time ranges, characterized by two different rate constants k1 and k2, respectively. The rate constants are of the order of 1014 s-1. k1 exhibits a maximum as a function of the absorbed energy Eabs, whereas k2 decreases as a function of Eabs.

  5. Stellar figure sensor

    NASA Technical Reports Server (NTRS)

    Peters, W. N.

    1973-01-01

    A compilation of analytical and experimental data is presented concerning the stellar figure sensor. The sensor is an interferometric device which is located in the focal plane of an orbiting large space telescope (LST). The device was designed to perform interferometry on the optical wavefront of a single star after it has propagated through the LST. An analytical model of the device was developed and its accuracy was verified by an operating laboratory breadboard. A series of linear independent control equations were derived which define the operations required for utilizing a focal plane figure sensor in the control loop for the secondary mirror position and for active control of the primary mirror.

  6. Figurative Language Awards Ceremony.

    ERIC Educational Resources Information Center

    Fink, Lisa

    Figurative language enlivens a text, providing visuals in the minds of readers. This lesson will have students listening to and reading selected texts as they seek out their favorite literary devices. During the five to seven 50-minute sessions, grade three through five students will: acquire a clear understanding of the concept of figurative…

  7. OECD in Figures, 2008

    ERIC Educational Resources Information Center

    OECD Publishing (NJ1), 2008

    2008-01-01

    "OECD in Figures" is a primary statistical source for key data on OECD countries, ranging from economic growth and employment to inflation, trade and environment. Information is presented in tabular form for: (1) Demography and Health; (2) Economy; (3) Energy; (4) Labour; (5) Science and Technology; (6) Environment; (7) Education; (8) Public…

  8. Recent developments in A2B adenosine receptor ligands.

    PubMed

    Kalla, Rao V; Zablocki, Jeff; Tabrizi, Mojgan Aghazadeh; Baraldi, Pier Giovanni

    2009-01-01

    A selective, high-affinity A(2B) adenosine receptor (AR) antagonist will be useful as a pharmacological tool to help determine the role of the A(2B)AR in inflammatory diseases and angiogenic diseases. Based on early A(2B)AR-selective ligands with nonoptimal pharmaceutical properties, such as 15 (MRS 1754: K(i)(hA(2B)) = 2 nM; K(i)(hA(1)) = 403 nM; K(i)(hA(2A)) = 503 NM, and K(i)(hA(3)) = 570 nM), several groups have discovered second-generation A(2B)AR ligands that are suitable for development. Scientists at CV Therapeutics have discovered the selective, high-affinity A(2B)AR antagonist 22, a 8-(4-pyrazolyl)-xanthine derivative, (CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM). Compound 22 has demonstrated favorable pharmacokinetic (PK) properties (T(1/2) = 4 h and F > 35% rat), and it is a functional antagonist at the A(2B)AR(K (B) = 6 nM). In a mouse model of asthma, compound 22 demonstrated a dose-dependent efficacy supporting the role of the A(2B)AR in asthma. In two Phase I clinical trails, 22 (CVT-6883) was found to be safe, well tolerated, and suitable for once-daily dosing. Baraldi et al. have independently discovered a selective, high-affinity A(2B)AR antagonist, 30 (MRE2029F20), 8-(5-pyrazolyl)-xanthine (K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) = 200 nM; K(i)(hA(2A), A(3)) > 1,000, that has been selected for development in conjunction with King Pharmaceuticals. Compound 30 has been demonstrated to be a functional antagonist of the A(2B)AR, and it has been radiolabeled for use in pharmacological studies. A third compound, 58 (LAS-38096), is a 2-aminopyrimidine derivative (discovered by the Almirall group) that has high A(2B)AR affinity and selectivity (K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM), and 58 has been moved into preclinical safety testing. A fourth selective, high-affinity A(2B)AR antagonist, 54 (OSIP339391 K(i))(hA(2B)) = 0.5 nM; K(i))(hA(1

  9. Advanced figure sensor operations and maintenance manual

    NASA Technical Reports Server (NTRS)

    Robertson, H. J.

    1972-01-01

    This manual contains procedures for installing, operating, and maintaining the optical figure sensor and its associated electronic controls. The optical figure sensor, a system of integrated components, comprises: (1) a phase measuring modified interferometer employing a single frequency 6328 A laser, and a Vidissector; (2) a two-axis automatic thermal compensation control mount; (3) a five degree of freedom manual adjustment stand; and (4) a control console. This instrument provides real time output data of optical figure errors for spherical mirrors, and is also capable of measuring aspherical mirrors if a null corrector is added.

  10. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... injection is in a class of medications called interferons. It works by stopping the growth of cancer ... allergic to peginterferon alfa-2b injection (PegIntron, Sylatron), interferon alfa-2b (Intron), any other medications, or any ...

  11. What Happened with Spectrometer Magnet 2B

    SciTech Connect

    Green, Michael A

    2010-05-27

    The spectrometer solenoid is supposed to be the first magnets installed in MICE [1]-[4]. This report described what happened during the test of the MICE spectrometer solenoid 2B. First, the report describes the temperatures in the magnet, the cooler top plate and the shield during the run where the magnet quenched at 258 A. During this quench, a lead between the bottom of the HTS leads and the diode bank burned out causing the magnet to quench. Second, three methods for measuring the net heat flow into the cold mass are described. Third, there is a discussion of possible resistive heating in the HTS leads between liquid helium temperature and the copper plate, which is at about 50 K. Fourth, there is a discussion of the measured first stage heat loads in the magnet, when there is no current in the magnet. The first stage heat load calculations are based on knowing the first stage temperatures of the three two-stage pulse tube coolers and the single stage GM cooler. Fifth, the estimated heat load to the first stage when the magnet has current in it is discussed. Sixth, there is a comparison of the stage 1 heat loads in magnet 1A [5], magnet 2A [6], and magnet 2B [7]. Finally there is a discussion of recommended changes for improving the spectrometer solenoids so that the coolers can keep them cold.

  12. Effects of sex and chronic neonatal nicotine treatment on Na²⁺/K⁺/Cl⁻ co-transporter 1, K⁺/Cl⁻ co-transporter 2, brain-derived neurotrophic factor, NMDA receptor subunit 2A and NMDA receptor subunit 2B mRNA expression in the postnatal rat hippocampus.

    PubMed

    Damborsky, J C; Winzer-Serhan, U H

    2012-12-01

    Chronic exposure to nicotine during the first postnatal week in rats, a developmental period that corresponds to the third trimester of human gestation, results in sexually dimorphic long-term functional defects in the adult hippocampus. One potential cause could be the sex-specific differences in the maturation of GABA(A) receptor-mediated responses from excitatory to inhibitory, which depends on the expression of the Na(2+)/K(+)/Cl(-) co-transporter 1 (NKCC1) and the K(+)/Cl(-) co-transporter 2 (KCC2). In the rat hippocampus, this switch occurs during the first and second postnatal week in females and males, respectively, and is regulated by nicotinic receptor activation. Excitatory GABAergic signaling can increase brain-derived neurotrophic factor (BDNF) expression, which might exacerbate sex differences by impacting synaptogenesis. We hypothesized that chronic neonatal nicotine (CNN) exposure differentially regulates the expression of these co-transporters and BDNF in males and females. We use quantitative isotopic in situ hybridization to examine the expression of mRNAs for NKCC1, KCC2, BDNF, and NMDA receptor subunit 2A (NR2A) and NMDA receptor subunit 2B (NR2B) in the postnatal day (P) 5 and 8 rat hippocampi in both sexes that were either control-treated or with 6mg/kg/day nicotine in milk formula (CNN) via gastric intubation starting at P1. In line with prolonged GABAergic excitation, we found that at P5 males had significantly higher mRNA expression of NKCC1 and BDNF than females. CNN treatment resulted in a significant increase in KCC2 and BDNF mRNA expression in male but not female hippocampus (p<0.05). Males also had higher expression of NR2A and lower expression of NR2B at P5 compared to females (p<0.05). At P8, there were neither sex nor treatment effects on mRNA expression, indicating the end of a critical period for sensitivity to nicotine. These results suggest that differential maturation of GABA(A)R-mediated responses result in sex

  13. Figuring Out Fat and Calories

    MedlinePlus

    ... I Help a Friend Who Cuts? Figuring Out Fat and Calories KidsHealth > For Teens > Figuring Out Fat ... the truth on fat and calories? What Are Fat and Calories? Fats, or lipids , are nutrients in ...

  14. Lunar Regolith Figures of Merit

    NASA Technical Reports Server (NTRS)

    Rickman, Doug; Scjrader. Cjrostoam; Jpe (zer. Jams); Fourroux, Kathy

    2009-01-01

    This viewgraph presentation reviews the lunar regolith figures of merit. The contents include: 1) A quick review of Figures-of-Merit (FoM); 2) Software Implementation of FoM Algorithms; and 3) Demonstration of the Software.

  15. GRIN2B predicts attention problems among disadvantaged children.

    PubMed

    Riva, Valentina; Battaglia, Marco; Nobile, Maria; Cattaneo, Francesca; Lazazzera, Claudio; Mascheretti, Sara; Giorda, Roberto; Mérette, Chantal; Émond, Claudia; Maziade, Michel; Marino, Cecilia

    2015-07-01

    It is well established that adversities and GRIN2B (coding an N-methyl-D-aspartate receptor subunit) are independently associated with behavioral and cognitive impairments in childhood. However, a high proportion of children exposed to adversities have good, long-term outcomes. We hypothesized that among children exposed to adversities, GRIN2B variants would predict the worst cognitive and behavioral outcomes. 6 single nucleotide polymorphisms of GRIN2B were genotyped in 625 children aged 6-11 years from an Italian community-based sample. The interacting effect of GRIN2B variants with 4 measures of adversities [low socioeconomic status (SES), preterm delivery, maternal smoking during pregnancy, and absence of breastfeeding] was investigated upon blindly assessed cognitive abilities (vocabulary, block design, digit spans of Wechsler's Intelligence Scale, and Rey complex figure) and parents-rated behavioral problems (Child Behavior Checklist/6-18). Rs2268119 × SES interaction (Hotelling's Trace = 0.07; F(12,1154) = 3.53; p = 0.00004) influenced behavior, with more attention problems among children in the 'either A/T or T/T genotype and low SES' group, compared to all other groups. This interaction effect was not significant in an independent, replication sample of 475 subjects from an Italian community-based sample. GRIN2B variants predict children with the worst outcome in attention functioning among children exposed to low SES. Our findings, if replicated, could help in the identification of children with the highest risk and may prompt cost-effective preventive/treatment strategies. PMID:25316095

  16. Making better scientific figures

    NASA Astrophysics Data System (ADS)

    Hawkins, Ed; McNeall, Doug

    2016-04-01

    In the words of the UK government chief scientific adviser "Science is not finished until it's communicated" (Walport 2013). The tools to produce good visual communication have never been so easily accessible to scientists as at the present. Correspondingly, it has never been easier to produce and disseminate poor graphics. In this presentation, we highlight some good practice and offer some practical advice in preparing scientific figures for presentation to peers or to the public. We identify common mistakes in visualisation, including some made by the authors, and offer some good reasons not to trust defaults in graphics software. In particular, we discuss the use of colour scales and share our experiences in running a social media campaign (http://tiny.cc/endrainbow) to replace the "rainbow" (also "jet", or "spectral") colour scale as the default in (climate) scientific visualisation.

  17. Crystal structure of eukaryotic translation initiation factor 2B.

    PubMed

    Kashiwagi, Kazuhiro; Takahashi, Mari; Nishimoto, Madoka; Hiyama, Takuya B; Higo, Toshiaki; Umehara, Takashi; Sakamoto, Kensaku; Ito, Takuhiro; Yokoyama, Shigeyuki

    2016-03-01

    Eukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of α-, β- and γ-subunits. eIF2B exchanges GDP for GTP on the γ-subunit of eIF2 (eIF2γ), and is inhibited by stress-induced phosphorylation of eIF2α. eIF2B is a heterodecameric complex of two copies each of the α-, β-, γ-, δ- and ε-subunits; its α-, β- and δ-subunits constitute the regulatory subcomplex, while the γ- and ε-subunits form the catalytic subcomplex. The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the α2β2δ2 hexameric regulatory subcomplex binds two γε dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross-linking method identified the eIF2α-binding and eIF2γ-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2γ-binding interface is located close to the conserved 'NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2α, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2α phosphorylation generates the 'nonproductive' eIF2-eIF2B complex, which prevents nucleotide exchange on eIF2γ, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control. PMID:26901872

  18. Investigation of Class 2b Trucks

    SciTech Connect

    Davis, S.C.

    2002-04-03

    The popularity of trucks in the class 2 category--that is, those with a 6,000 to 10,000 pounds (lbs) gross vehicle weight rating (GVWR)--has increased since the late 1970s/early 1980s. The purpose of this research is to identify and examine vehicles in the upper portion of the class 2 weight range (designated as vehicle class 2b) and to assess their impact. Vehicles in class 2b (8,500-10,000 lbs GVWR) include pickup trucks, sport utility vehicles (SUVs), and large vans (i.e., not minivans). Oak Ridge National Laboratory researched each individual truck model to determine which models were class 2b trucks and arrived at four methodologies to derive sales volumes. Two methods--one for calendar year and one for model year sales--were recommended for producing believable and reliable results. The study indicates that 521,000 class 2b trucks were sold in calendar year 1999--6.4% of sales of all trucks under 10,000 lbs. Eighty-two percent of class 2b trucks sold in 1999 were pickups; one third of class 2b trucks sold in 1999 were diesel. There were 5.8 million class 2b trucks on the road in 2000, which amounts to 7.8% of all trucks under 10,000 lbs. Twenty-four percent of the class 2b truck population is diesel. Estimates show that class 2b trucks account for 8% of annual miles traveled by trucks under 10,000 lbs and 9% of fuel use. Data on class 2b trucks are scarce. As the Tier 2 standards, which apply to passenger vehicles in the 8,500-10,000 lb GVWR category, become effective, additional data on class 2b trucks may become available--not only emissions data, but data in all areas. At the moment, distinguishing class 2b trucks from class 2 trucks in general is a substantial task requiring data on an individual model level.

  19. Peginterferon Alfa-2b Injection (Sylatron)

    MedlinePlus

    ... 2b injection is used in people with malignant melanoma (a life-threatening cancer that begins in certain ... is used to reduce the chance that malignant melanoma will come back and must be started within ...

  20. Peginterferon Alfa-2b (PEG-Intron)

    MedlinePlus

    ... inject into your stomach if you are very thin. Use a different spot for each injection. Do not inject peginterferon alfa-2b into an area where the skin is sore, red, bruised, scarred, irritated, or infected; has stretch marks ...

  1. Figure Analysis: An Implementation Dialogue

    ERIC Educational Resources Information Center

    Wiles, Amy M.

    2016-01-01

    Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver…

  2. Three-Dimensional Lissajous Figures.

    ERIC Educational Resources Information Center

    D'Mura, John M.

    1989-01-01

    Described is a mechanically driven device for generating three-dimensional harmonic space figures with different frequencies and phase angles on the X, Y, and Z axes. Discussed are apparatus, viewing stereo pairs, equations of motion, and using space figures in classroom. (YP)

  3. Scientific core hole Valles caldera No. 2b (VC-2b), New Mexico

    SciTech Connect

    Garner, J.N.; Hulen, J.B.; Lysne, P.; Jacobson, R.; Goff, F.; Nielson, D.L.; Pisto, L.; Criswell, C.W.; Gribble, R.; Utah Univ. Research Inst., Salt Lake City, UT; Sandia National Labs., Albuquerque, NM; Los Alamos National Lab., NM; Utah Univ. Research Inst., Salt Lake City, UT; Tonto Drilling Services, Inc., Salt Lake City, UT; Los Alamo

    1989-01-01

    Research core hole was continuously cored to 1.762 km on the western flank of the caldera's resurgent dome in 1988. Bottom hole temperature is about 295{degree}C within Precambrian (1.5 Ga) quartz monzonite, deep within the liquid-dominated portions of the Sulphur Springs hydrothermal system. VC-2b may be the deepest, hottest, continuously cored hole in North America. Core recovery was 99.2%. The only major drilling problems encountered were when temperatures at the bit exceeded 225{degree}C below depths of about 1000 m. The result of these conditions was loss of viscosity and/or lubricity in the mud, apparently caused by breakdown of the high temperature polymers. Lithologies in caldera-fill indicate the drill site may be proximal to ignimbrite vents and that an intracaldera lake with temperatures approaching boiling formed soon after the caldera itself. Structural correlations between VC-2b and the 528-m-deep companion hole VC-2a indicate the earlier Toledo caldera (1.45 Ma; Otowi Member tuffs) and even older Lower Tuffs caldera experienced no structural resurgence similar to the 1.12 million year old Valles caldera. The hydrothermal system penetrated by these bores, consists of a shallow vapor-rich cap, which has evolved from an earlier 200{degree}C liquid-dominated system, overlying stacked, liquid-dominated zones up to about 300{degree}C. Geochemistry of mud returns collected during drilling suggests chloride-rich geothermal fluids were entering the bore and mixing with the drilling fluids in the fractured lower Paleozoic and Precambrian sections. 23 refs., 5 figs., 1 tab.

  4. Cancer Facts and Figures 2014

    MedlinePlus

    ... Facts & Figures 2014 This annual report provides the estimated numbers of new cancer cases and deaths in ... and treatment. In 2014, there will be an estimated 1,665,540 new cancer cases diagnosed and ...

  5. A2B adenosine receptor activity is reduced in neutrophils from patients with systemic sclerosis

    PubMed Central

    Bazzichi, Laura; Trincavelli, Letizia; Rossi, Alessandra; De Feo, Francesca; Lucacchini, Antonio; Bombardieri, Stefano; Martini, Claudia

    2005-01-01

    We conducted the present study to investigate protein expression and functioning of A2A and A2B adenosine receptors (ARs) in neutrophils of patients affected by systemic sclerosis (SSc). The presence of A2A and A2B ARs was assessed by immunoblotting using specific antibodies. Equilibrium A2A and A2B ARs binding parameters were evaluated by radioligand binding assay. Functional studies were conducted to investigate coupling of the A2B AR to the adenylyl cyclase pathway. This is the first report of the use of Western blot analysis to confirm the presence of A2A and A2B ARs in human neutrophils. No significant changes in A2A AR binding parameters or expression levels were detected between SSc patients and healthy control individuals. A significant decrease (65%) in the maximum density of A2B AR binding sites occurred in SSc neutrophils, whereas no changes in the affinity constant values were found. Moreover, a decrease in A2B AR mediated adenylyl cyclase activity was observed in patients with SSc. Our findings demonstrate the occurrence of selective alterations in A2B AR density and signalling in SSc. PMID:15743465

  6. Vegetation Red-edge Spectral Modeling for Solar-induced Chlorophyll Fluorescence Retrieval at O2-B Band

    NASA Astrophysics Data System (ADS)

    Huang, C.; Zhang, L.; Qiao, N.; Zhang, X.; Li, Y.

    2015-12-01

    Remotely sensed solar-induced chlorophyll fluorescence (SIF) has been considered an ideal probe in monitoring global vegetation photosynthesis. However, challenges in accurate estimate of faint SIF (less than 5% of the total reflected radiation in near infrared bands) from the observed apparent reflected radiation greatly limit its wide applications. Currently, the telluric O2-B (~688nm) and O2-A (~761nm) have been proved to be capable of SIF retrieval based on Fraunhofer line depth (FLD) principle. They may still work well even using conventional ground-based commercial spectrometers with typical spectral resolutions of 2~5 nm and high enough signal-to-noise ratio (e.g., the ASD spectrometer). Nevertheless, almost all current FLD based algorithms were mainly developed for O2-A, a few concentrating on the other SIF emission peak in O2-B. One of the critical reasons is that it is very difficult to model the sudden varying reflectance around O2-B band located in the red-edge spectral region (about 680-800 nm). This study investigates a new method by combining the established inverted Gaussian reflectance model (IGM) and FLD principle using diurnal canopy spectra with relative low spectral resolutions of 1 nm (FluorMOD simulations) and 3 nm (measured by ASD spectrometer) respectively. The IGM has been reported to be an objective and good method to characterize the entire vegetation red-edge reflectance. Consequently, the proposed SIF retrieval method (hereinafter called IGMFLD) could exploit all the spectral information along the whole red-edge (680-800 nm) to obtain more reasonable reflectance and fluorescence correction coefficients than traditional FLD methods such as the iFLD. Initial results show that the IGMFLD can better capture the spectrally non-linear characterization of the reflectance in 680-800 nm and thereby yields much more accurate SIFs in O2-B than typical FLD methods, including sFLD, 3FLD and iFLD (see figure 1). Finally, uncertainties and prospect

  7. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-01

    Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver information to students. Here, a "how to" guide is presented in the form of an in-class dialogue, displaying the difficulties in visual interpretation that some students may experience while figure analysis is being implemented in an upper-level, cell biology course. Additionally, the dialogue serves as a guide for instructors who may implement the active learning technique as they consider how to respond to students' concerns in class. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):345-348, 2016. PMID:26892173

  8. First identification of Porcine Circovirus Type 2b mutant in pigs from Uruguay.

    PubMed

    Ramos, Natalia; Mirazo, Santiago; Castro, Gustavo; Arbiza, Juan

    2015-07-01

    Porcine Circovirus Type 2 (PCV2) is a worldwide distributed virus and is considered an important emerging pathogen related to several distinct disease syndromes in pigs. PCV2 strains are classified into three genotypes: PCV2a, with five subtypes (2A-2E), PCV2b with three subtypes (1A-1C) and PCV2c, only found in Denmark. Recently, several reports suggested the circulation of newly emerging PCV2b mutants (mPCV2b) isolated from pigs with PCVAD in cases of suspected vaccine failure. In this work, we report for the first time the identification of mPCV2b in pigs from Uruguay, providing an additional evidence of a global circulation. Complete genome characterization and phylogenetic analysis reveal that Uruguayan strains, as well as mPCV2b previously reported are closely related to other sequences already classified as PCV2b-1C. Furthermore, results showed that mPCV2b presented different genetic markers in the capsid protein compared with classical PCV2a/b strains. Further investigation about antigenic shift of the mPCV2b strains including the Uruguayan isolates is needed. PMID:26004195

  9. Choreography Styles in Figure Skating

    ERIC Educational Resources Information Center

    Moormann, Peter Paul

    2006-01-01

    Fifty-eight figure skating trainers from fifteen different countries acted as volunteers in this study on choreography styles. The styles were based on reports of artistic-creative strategies in composing music, drawing, writing poems or novels, and in making dances. The prevalence of the Mozartian (at the onset the choreographer already has a…

  10. A Figural Education with Lyotard

    ERIC Educational Resources Information Center

    Ford, Derek R.

    2015-01-01

    While there was a flurry of articles throughout the 1990s in philosophy of education on Lyotard, there are still several key concepts in his "oeuvre" that have import for but remain largely underdeveloped or absent in the field. One of the most interesting of these absent concepts is Lyotard's notion of the figural. In this paper, I…

  11. Figuring out a scientific understanding

    NASA Astrophysics Data System (ADS)

    Sutton, Clive

    1993-12-01

    This article attempts to place analogy and metaphor within the wider context of all figurative language, and to trace the relationship between that kind of expression and the supposedly literal and direct accounts of nature that scientists have built up.I explore the functions of figures of speech in the development of new scientific ideas, and trace how they fade or die as each area of scientific knowledge matures. What we then take to be the literal words of scientific description are in effect the remnants of old figures of speech that have grown so familiar that their earlier metaphorical quality is easily overlooked. The conventional separation of figurative and literal cannot be sustained, and a new understanding of their relationship is needed.The practical implications of this analysis are to do with how we can reactivate the dormant metaphors in ordinary scientific language, so that learners may hear again the human voice of scientists who developed the ways of talking we now take for granted. To reactivate the system of thought behind any established way of talking, we must be able to get the learners to understand that language works as a medium of interpretation and persuasion, and not simply a system of descriptive labeling. These two views of language are compared and contrasted.

  12. Storytelling Figures: A Pueblo Tradition.

    ERIC Educational Resources Information Center

    Kraus, Nancy

    1997-01-01

    In a collaborative unit on pueblo storytelling figures involving art, music, language arts, and physical education, a teacher describes how she helped second graders understand the Pueblo pottery tradition by reading aloud literature covering the past and present. Lists folklore, fiction, poetry, nonfiction, professional resources, videos, CDs,…

  13. The contributions of figure and ground textures to segmentation.

    PubMed

    Bravo, M J; Blake, R

    1992-09-01

    Several models of texture segmentation use spatial gradients in the activity of early filters to locate texture boundaries. The models assume that these filters are identical to those involved in the detection and discrimination of near threshold patterns. The models differ in how activity gradients from different types of filters are combined. We examined this question by measuring the respective contributions of a figure and a ground texture to segmentation. Vertical and horizontal line segments were used to construct two perfectly discriminable textures and these textures were used to construct four types of displays. Each display contained an obliquely oriented figure, but the displays differed in the way this figure was defined. Displays consisted of either (1) a horizontally textured figure on a blank background, (2) a blank figure on a vertically textured background, (3) a horizontally textured figure on a vertically textured background or (4) a figure with a mixed texture (50% vertical lines, 50% horizontal lines) on a blank background. In a two-alternative forced-choice experiment, observers were asked to judge the figure's orientation (right or left oblique), and the contrast of the textures was varied across trials. The resulting psychometric functions for segmentation were very similar for the four types of displays, suggesting ways in which a simple model of segmentation should be modified. PMID:1455752

  14. The estimate on lunar figure

    NASA Astrophysics Data System (ADS)

    Gao, B. X.

    2008-10-01

    In 1799 Laplace had discovered that the lunar three principal momentum are not in equilibrium with the Moon's current orbital and rotational state.Some authors suggested that the Moon may carry a fossil figure. Before more 3 billion years the liquid Moon was closer to the Earth and revolved faster.Then the Moon migrated outwards and revolved slow down. During the early part of this migration, the Moon was continually subjected to tidal and rotational stretching and formed into an ellipsoid. Then the Moon cooled and solidified quickly. Eventually, the solid Moon's lithosphere was stable, so that we may see the very early lunar figure. In this paper, by using the lunar libration parameters and the spherical-harmonic gravity coefficient, the length of three radii a, b, c of the ellipsoid and the Moon's figure as an equilibrium tidal have been calculated. Then three conclusions can be obtained; (1) In the beginning the Moon may be very close to the Earth, before about 3 billion years the moon may cooled and solidified, and the present Moon are in the fossil figure. (2) In the third section of this paper, we demonstrate that the tidal deformation of liquid Moon was 1.934 times then the equilibrium tide. So that if to calculating the true lunar figure by using the lunar spherical-harmonic gravity coefficients, the effects of Liquid Love number hf = 1.934must be considered. (3) According to the difference between a, b, and c, the lunar distance (1.7455×108m) and spin period 3.652day can be calculated. So that the lunar orbits period was 8.34day. Hence the Moon was locked closely into a resonance orbit in the ratio 2:1 when the Moon froze.

  15. Cloning and chromosomal localization of the human A{sub 2b} adenosine receptor gene (ADORA2B) and its pseudogene

    SciTech Connect

    Jacobson, M.A.; Johnson, R.G.; Luneau, C.J.

    1995-05-20

    To determine the chromosomal localization of the human A{sub 2b} adenosine receptor, the corresponding genomic clone was isolated and used as a probe for fluorescence in situ hybridization to metaphase chromosomes. Partial sequence analysis of the A{sub 2b} gene (ADORA2B) revealed an intron that interrupted the coding region corresponding to the second intracellular loop similar to that reported for A{sub 1} and A{sub 2a} adenosine receptor genes. A pseudogene for the A{sub 2b} receptor was also identified; it exhibited 79% identity to the A{sub 2b} adenosine receptor cDNA coding sequence and contained multiple deletions, point mutations, and frame shifts and two in-frame stops. These changes would result in the inability to encode a functional receptor. The genomic clones were utilized to localize the A{sub 2b} receptor to chromosome 17p12 and the A{sub 2b} pseudogene to chromosome 1q32. 15 refs., 1 fig.

  16. Obliquely incident ion beam figuring

    NASA Astrophysics Data System (ADS)

    Zhou, Lin; Dai, Yifan; Xie, Xuhui; Li, Shengyi

    2015-10-01

    A new ion beam figuring (IBF) technique, obliquely incident IBF (OI-IBF), is proposed. In OI-IBF, the ion beam bombards the optical surface obliquely with an invariable incident angle instead of perpendicularly as in the normal IBF. Due to the higher removal rate in oblique incidence, the process time in OI-IBF can be significantly shortened. The removal rates at different incident angles were first tested, and then a test mirror was processed by OI-IBF. Comparison shows that in the OI-IBF technique with a 30 deg incident angle, the process time was reduced by 56.8%, while keeping the same figure correcting ability. The experimental results indicate that the OI-IBF technique is feasible and effective to improve the surface correction process efficiency.

  17. Comparison of three commercial one-dose porcine circovirus type 2 (PCV2) vaccines in a herd with concurrent circulation of PCV2b and mutant PCV2b.

    PubMed

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2015-05-15

    Porcine circovirus associated disease (PCVAD) occurred in a farm where pigs had been routinely vaccinated with a commercial PCV2a vaccine. A mutant PCV2b (mPCV2b) was isolated from pigs with PCVAD, perhaps implying a perceived vaccine failure. The objective of this study was to determine and compare the efficacy of 3 one-dose PCV2a vaccines of varying antigen type and dose in the same pig farm with concurrent PCV2b and mPCV2b infection based on clinical (average daily weight gain; ADWG), virological (evidence of viremia), immunological (presence of PCV2-specific neutralizing antibody; NA and interferon-γ secreting cells; IFN-γ-SC), and pathological (lymphoid lesion and PCV2 antigen score within lesion) evaluation. Regardless of which commercial PCV2a vaccine was used, vaccinated animals improved ADWG, and reduced the amount of PCV2b and mPCV2b load in the blood compared to unvaccinated animals. The vaccination of piglets at 3 weeks of age effectively induced higher levels of PCV2b- and mPCV2b-specific NA and IFN-γ-SC compared to unvaccinated animals. A reduction in mPCV2b load in the blood coincided with the appearance of both mPCV2b-specific NA and IFN-γ-SC in the vaccinated animals. The microscopic lymphoid lesions and PCV2-antigen scores within the lymph nodes were significantly lower in vaccinated animals. The perceived vaccine failure could not be explained by incomplete protection of the commercial PCV2a vaccine against mPCV2b. The results of the present study demonstrated that currently available commercial PCV2a vaccines are protective against concurrent PCV2b and mPCV2b infection based on clinical, virological, immunological, and pathological evaluations under field conditions. PMID:25790733

  18. Noncanonical sortase-mediated assembly of pilus type 2b in group B Streptococcus.

    PubMed

    Lazzarin, Maddalena; Cozzi, Roberta; Malito, Enrico; Martinelli, Manuele; D'Onofrio, Mariapina; Maione, Domenico; Margarit, Immaculada; Rinaudo, C Daniela

    2015-11-01

    Group B Streptococcus (GBS) expresses 3 structurally distinct pilus types (1, 2a, and 2b) identified as important virulence factors and vaccine targets. These pili are heterotrimeric polymers, covalently assembled on the cell wall by sortase (Srt) enzymes. We investigated the pilus-2b biogenesis mechanism by using a multidisciplinary approach integrating genetic, biochemical, and structural studies to dissect the role of the 2 pilus-2b-associated Srts. We show that only 1 sortase (SrtC1-2b) is responsible for pilus protein polymerization, whereas the second one (Srt2-2b) does not act as a pilin polymerase, but similarly to the housekeeping class A Srt (SrtA), it is involved in cell-wall pilus anchoring by targeting the minor ancillary subunit. Based on its function and sequence features, Srt2-2b does not belong to class C Srts (SrtCs), nor is it a canonical member of any other known family of Srts. We also report the crystal structure of SrtC1-2b at 1.9 Å resolution. The overall fold resembles the typical structure of SrtCs except for the N-terminal lid region that appears in an open conformation displaced from the active site. Our findings reveal that GBS pilus type 2b biogenesis differs significantly from the current model of pilus assembly in gram-positive pathogens. PMID:26202865

  19. Axial Magnetic Anisotropy from Two Systems Fe2B and Co2B with Planar Anisotropy

    NASA Astrophysics Data System (ADS)

    Taufour, Valentin; Lamichhane, Tej; Bud'Ko, Sergey L.; Jesche, Anton; Goldman, Alan I.; Dennis, Kevin W.; McCallum, R. William; Antropov, Vladimir; Canfield, Paul C.

    2015-03-01

    Growth of single crystals of (Fe1-xCox)2B (0 <= x <= 1) and detailed characterization of their magnetic properties will be presented. Despite the fact that both Fe2B and Co2B show a planar anisotropy at room temperature, we observe a uniaxial anisotropy at intermediate doping which makes (Fe,Co)2B a promising system for permanent magnet applications in a system without rare-earth element. Comparison with recent band structure calculations will be presented. The temperature dependence of the anisotropy measured on single crystals from 2 K to 1000 K shows some unusual variations with an increase of the magnetic anisotropy with increasing temperature at some specific substitution. This work is supported by the Critical Materials Institute, an Energy Innovation Hub funded by the US DOE and by the Office of Basic Energy Science, Division of Materials Science and Engineering. Ames Laboratory is operated for the US DOE by Iowa State University under Contract No. DE-AC02-07CH11358.

  20. Enhanced spatial resolution on figures versus grounds.

    PubMed

    Hecht, Lauren N; Cosman, Joshua D; Vecera, Shaun P

    2016-07-01

    Much is known about the cues that determine figure-ground assignment, but less is known about the consequences of figure-ground assignment on later visual processing. Previous work has demonstrated that regions assigned figural status are subjectively more shape-like and salient than background regions. The increase in subjective salience of figural regions could be caused by a number of processes, one of which may be enhanced perceptual processing (e.g., an enhanced neural representation) of figures relative to grounds. We explored this hypothesis by having observers perform a perceptually demanding spatial resolution task in which targets appeared on either figure or ground regions. To rule out a purely attentional account of figural salience, observers discriminated targets on the basis of a region's color (red or green), which was equally likely to define the figure or the ground. The results of our experiments showed that targets appearing on figures were discriminated more accurately than those appearing in ground regions. In addition, targets appearing on figures were discriminated better than those presented in regions considered figurally neutral, but targets appearing within ground regions were discriminated more poorly than those appearing in figurally neutral regions. Taken together, our findings suggest that when two regions share a contour, regions assigned as figure are perceptually enhanced, whereas regions assigned as ground are perceptually suppressed. PMID:27048441

  1. Hooke's figurations: a figural drawing attributed to Robert Hooke.

    PubMed

    Hunter, Matthew C

    2010-09-20

    The experimental philosopher Robert Hooke (1635-1703) is known to have apprenticed to the leading painter Peter Lely on his first arrival in London in the late 1640s. Yet the relevance of Hooke's artistic training to his mature draughtsmanship and identity has remained unclear. Shedding light on that larger interpretive problem, this article argues for the attribution to Hooke of a figural drawing now in Tate Britain (T10678). This attributed drawing is especially interesting because it depicts human subjects and bears Hooke's name functioning as an artistic signature, both highly unusual features for his draughtsmanship. From evidence of how this drawing was collected and physically placed alongside images by leading artists in the early eighteenth century, I suggest how it can offer new insight into the reception of Hooke and his graphic work in the early Enlightenment. PMID:20973449

  2. Synthesis and Electrochemical Properties of Nano-VO2 (B).

    PubMed

    Yang, Yun; Lu, Yong; Wang, Wei; Feng, Chuanqi; Yang, Shuijin

    2016-03-01

    The nano-VO2 (B) has been self-assembly synthesized by hydrothermal method using different templates, which may give them some interesting properties. The as-prepared samples were characterized by X-ray powder diffraction (XRD) and scanning electron microscopy (SEM). The electrochemical properties of the samples were investigated. The results show that the hexadecyltrimethyl ammonium bromide (CTAB) (soft template) was used to obtain the VO2 (B1) nanobelts. The flake graphite (hard template) was taken to get the VO2 (B2) nanosheets. The VO2 (B1) nanobelts have higher initial capacity to compare with VO2 (B2). But the VO2 (B2) nanosheets showed better cycling performance than that of VO2 (B1) nanobelts. The nano VO2 (B2) is a promising anode material for lithium ion battery application. PMID:27455666

  3. 49 CFR Appendix - Figures to Part 38

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Figures to Part 38 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, and similar vehicles, and systems Pt. 38, Figures Figures to Part 38 ER28SE98.000...

  4. 49 CFR Appendix - Figures to Part 38

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Figures to Part 38 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, and similar vehicles, and systems Pt. 38, Figures Figures to Part 38 ER28SE98.000...

  5. Preadolescent male perceptions of action figure physiques.

    PubMed

    Baghurst, Timothy; Carlston, David; Wood, Julie; Wyatt, Frank B

    2007-12-01

    This study investigated the preference and reasoning of 176 preadolescent and adolescent males when presented with original and current action figures that had statistically different physiques. Current action figures were perceived as significantly more muscular and healthier. Participants also preferred to resemble current action figures citing muscularity and size for their preference. PMID:18023792

  6. 49 CFR Appendix - Figures to Part 38

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Figures to Part 38 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, and similar vehicles, and systems Pt. 38, Figures Figures to Part 38 ER28SE98.000...

  7. 49 CFR Appendix - Figures to Part 38

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 1 2011-10-01 2011-10-01 false Figures to Part 38 Transportation Office of the Secretary of Transportation AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY SPECIFICATIONS FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, and similar vehicles, and systems Pt. 38, Figures Figures to Part 38 ER28SE98.000...

  8. PHOBOS Experiment: Figures and Data

    DOE Data Explorer

    The PHOBOS Collaboration

    PHOBOS consists of many silicon detectors surrounding the interaction region. With these detectors physicists can count the total number of produced particles and study the angular distributions of all the products. Physicists know from other branches of physics that a characteristic of phase transitions are fluctuations in physical observables. With the PHOBOS array they look for unusual events or fluctuations in the number of particles and angular distribution. The articles that have appeared in refereed science journals are listed here with separate links to the supporting data plots, figures, and tables of numeric data.  See also supporting data for articles in technical journals at http://www.phobos.bnl.gov/Publications/Technical/phobos_technical_publications.htm and from conference proceedings at http://www.phobos.bnl.gov/Publications/Proceedings/phobos_proceedings_publications.htm

  9. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  10. 7 CFR 301.80-2b - Exempted articles. 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 5 2013-01-01 2013-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  11. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 5 2011-01-01 2011-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  12. 7 CFR 301.85-2b - Exempted articles. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.85-2b Section 301.85-2b... § 301.85-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines and other provisions of this subpart. (a) The following articles...

  13. 7 CFR 301.80-2b - Exempted articles. 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 5 2010-01-01 2010-01-01 false Exempted articles. 1 301.80-2b Section 301.80-2b....80-2b Exempted articles. 1 1 The articles hereby exempted remain subject to applicable restrictions under other quarantines. (a) The following articles are exempt from the certification and permit...

  14. Hydroxysteroid sulfotransferase 2B1b expression and localization in normal human brain

    PubMed Central

    Salman, Emily D.; Faye-Petersen, Ona; Falany, Charles N.

    2012-01-01

    Steroid sulfonation in the human brain has not been well characterized. The major sulfotransferase (SULT) isoforms that conjugate steroids in humans are SULT1E1, SULT2A1, and SULT2B1b. SULT2B1b catalyzes the sulfonation of 3β-hydroxysteroids, including neurosteroids dehydroepiandrosterone and pregnenolone, as well as cholesterol and several hydroxycholesterols. SULT2B1b mRNA and protein expression were detected in adult and fetal human brain sections, whereas neither mRNA, nor protein expression were identified for SULT1E1 or SULT2A1. Using immunohistochemical analysis, SULT2B1b expression was detected in neurons and oligodendrocytes in adult brain and in epithelial tissues in 28-week-old fetal brain. Sulfonation of cholesterol, oxysterols, and neurosteroids in the brain is apparently catalyzed by SULT2B1b since expression of neither SULT2A1 nor SULT1E1 was detected in human brain sections. SULT2B1b mRNA and protein were also detected in human U373-MG glioblastoma cells. Both mRNA and protein expression of liver X receptor (LXR)-β, but not LXR-α, were detected in U373-MG cells, and LXR-β activation resulted in a decrease in SULT2B1b protein expression. Since hydroxycholesterols are important physiological LXR activators, this suggests a role for regulation of sterol metabolism by LXR and SULT2B1b. Therefore, elucidating key enzymes in the metabolism of cholesterol and neurosteroids could help define the properties of steroid conjugation in the human brain. PMID:24683427

  15. Complex Alternative Splicing of the Smarca2 Gene Suggests the Importance of Smarca2-B Variants

    PubMed Central

    Yang, Min; Sun, Yuan; Ma, Ling; Wang, Chenguang; Wu, Jian-min; Bi, Anding; Liao, D. Joshua

    2011-01-01

    BRM is an ATPase component of the SWI/SNF complex that regulates chromatin remodeling and cell proliferation and is considered a tumor suppressor. In this study we characterized transcripts from the Smarca2 gene that encodes the BRM protein. We found that the human Smarca2 gene (hSmarca2), like its mouse counterpart (mSmarca2), also initiated a short transcript from intron 27 of the long transcript. We name the long and short transcripts as Smarca2-a and Smarca2-b, respectively. Like its human counterpart, mSmarca2-a also underwent alternative splicing at the 54-bp exon 29. The hSmarca2-b had two alternative initiation sites and underwent alternative splicing at three different 3' sites of exon 1 and at exons 2, 3 and/or 5. We identified nine hSmarca2-b mRNA variants that might produce five different proteins. mSmarca2-b also underwent alternative splicing at exon 3 and/or exon 5, besides alternatively retaining part of intron 1 in exon 1. Smarca2-b was expressed more abundantly than Smarca2-a in many cell lines and was more sensitive to serum starvation. Moreover, cyclin D1 also regulated the expression of both Smarca2-a and Smarca2-b in a complex manner. These data suggest that the functions of the Smarca2 gene may be very complex, not just simply inhibiting cell proliferation, and in certain situations may be elicited mainly by expressing the much less known Smarca2-b, not the better studied Smarca2-a and its products BRM proteins. PMID:21811517

  16. Antigenic Determinants of Possible Vaccine Escape by Porcine Circovirus Subtype 2b Viruses

    PubMed Central

    Constans, Megan; Ssemadaali, Marvin; Kolyvushko, Oleksandr; Ramamoorthy, Sheela

    2015-01-01

    Currently available commercial vaccines against porcine circovirus strain 2 (PCV2) solely target the PCV2a genotype. While PCV2 vaccines are highly effective in preventing clinical signs, PCV2b has dominated over the PCV2a genotype in prevalence, corresponding with the introduction of PCV2a vaccines. A recently emerged PCV2b recombinant with an additional amino acid in the capsid protein, designated the mutant PCV2b (mPCV2b), is cause for concern due to its increased virulence and rapid spread. The accumulation of recent evidence for the increased genetic diversity in PCV2 suggests that current vaccines against PCV2a may be inducing selection pressure and driving viral evolution. In this study, the hypothesis that differences in key immune epitopes between the PCV2a vaccine strains, a classical PCV2b strain called PCV2b 41513 obtained from a vaccine-failure case, and mPCV2b strains could promote vaccine escape was tested using immuno-informatic tools. In the major viral proteins, 9 of the 18 predicted swine leukocyte antigens (SLA) class-I epitopes, 8 of the 22 predicted SLA class-II epitopes, and 7 of the 25 predicted B cell epitopes varied between the vaccine and field strains. A majority of the substitutions in both the T- and B-cell epitopes were located in the capsid protein. Some B- and T-cell epitopes that were identified as immunogenic in the vaccine strain were not identified as epitopes in the field strains, indicating a subtle shift in the antigenic profile of the field strains. Several nonconserved epitopes had both predicted B- and T-cell functions. Therefore, substitutions in the dual epitopes could affect both arms of the immune response simultaneously, causing immune escape. Our findings support further rational design of PCV2 vaccines to increase the current threshold of protection. PMID:26339187

  17. PHOX2B is a suppressor of neuroblastoma metastasis

    PubMed Central

    Naftali, Osnat; Maman, Shelly; Meshel, Tsipi; Sagi-Assif, Orit; Ginat, Ravit; Witz, Isaac P.

    2016-01-01

    Paired like homeobox 2B (PHOX2B) is a minimal residual disease (MRD) marker of neuroblastoma. The presence of MRD, also referred to as micro-metastases, is a powerful marker of poor prognosis in neuroblastoma. Lung metastasis is considered a terminal event in neuroblastoma. Lung micro-metastatic neuroblastoma (MicroNB) cells show high expression levels of PHOX2B and possess a less malignant and metastatic phenotype than lung macro metastatic neuroblastoma (MacroNB) cells, which hardly express PHOX2B. In vitro assays showed that PHOX2B knockdown in MicroNB cells did not affect cell viability; however it decreased the migratory capacity of the MicroNB-shPHOX2B cells. An orthotopic inoculation of MicroNB-shPHOX2B cells into the adrenal gland of nude mice resulted in significantly larger primary tumors and a heavier micro-metastatic load in the lungs and bone-marrow, than when control cells were inoculated. PHOX2B expression was found to be regulated by methylation. The PHOX2B promoter in MacroNB cells is significantly more methylated than in MicroNB cells. Demethylation assays using 5-azacytidine demonstrated that methylation can indeed inhibit PHOX2B transcription in MacroNB cells. These pre-clinical data strongly suggest that PHOX2B functions as a suppressor of neuroblastoma progression. PMID:26840262

  18. 50 CFR Figure 1 to Part 648 - Figure 1 to Part 648

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Figure 1 to Part 648 1 Figure 1 to Part 648 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Pt. 648, Figure 1 Figure 1...

  19. 50 CFR Figure 1 to Part 648 - Figure 1 to Part 648

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Figure 1 to Part 648 1 Figure 1 to Part 648 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Pt. 648, Figure 1 Figure 1...

  20. 50 CFR Figure 1 to Part 648 - Figure 1 to Part 648

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Figure 1 to Part 648 1 Figure 1 to Part 648 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Pt. 648, Figure 1 Figure 1...

  1. 50 CFR Figure 1 to Part 648 - Figure 1 to Part 648

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Figure 1 to Part 648 1 Figure 1 to Part 648 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Pt. 648, Figure 1 Figure 1...

  2. H-2b bound to egg lecithin liposomes: biochemical and functional properties.

    PubMed Central

    Rogers, M J

    1982-01-01

    Purified H-2b and H-2a molecules were bound to egg lecithin liposomes by a detergent dialysis procedure. Analysis of the liposomes indicated that only 30-50% of bound H-2b is oriented with the hydrophilic, antigenic portion of the molecule toward the outside of the liposome. Saturation of the liposomes occurred at a ratio of 64 molecules of egg lecithin per molecule of H-2b. Liposomes containing H-2 molecules were capable of stimulating spleen cells from primed donors to produce specific, alloreactive, cytotoxic T lymphocytes in vitro. Stimulation was dependent on adherent cells present in the responder spleen cells. Optimal stimulation occurred with highly saturated liposomes and at a ratio of 4-8 micrograms of H-2b per 8 X 10(6) responder cells. Images Fig. 4 PMID:7116686

  3. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation

    PubMed Central

    Pon, Julia R.; Wong, Jackson; Saberi, Saeed; Alder, Olivia; Moksa, Michelle; Grace Cheng, S. -W.; Morin, Gregg B.; Hoodless, Pamela A.; Hirst, Martin; Marra, Marco A.

    2015-01-01

    Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial–mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis. PMID:26245647

  4. MEF2B mutations in non-Hodgkin lymphoma dysregulate cell migration by decreasing MEF2B target gene activation.

    PubMed

    Pon, Julia R; Wong, Jackson; Saberi, Saeed; Alder, Olivia; Moksa, Michelle; Grace Cheng, S-W; Morin, Gregg B; Hoodless, Pamela A; Hirst, Martin; Marra, Marco A

    2015-01-01

    Myocyte enhancer factor 2B (MEF2B) is a transcription factor with mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL). To provide insight into the regulatory network of MEF2B, in this study, we analyse global gene expression and DNA-binding patterns. We find that candidate MEF2B direct target genes include RHOB, RHOD, CDH13, ITGA5 and CAV1, and that indirect target genes of MEF2B include MYC, TGFB1, CARD11, MEF2C, NDRG1 and FN1. MEF2B overexpression increases HEK293A cell migration and epithelial-mesenchymal transition, and decreases DLBCL cell chemotaxis. K4E, Y69H and D83V MEF2B mutations decrease the capacity of MEF2B to activate transcription and decrease its' effects on cell migration. The K4E and D83V mutations decrease MEF2B DNA binding. In conclusion, our map of the MEF2B regulome connects MEF2B to drivers of oncogenesis. PMID:26245647

  5. PTK2b function during fertilization of the mouse oocyte

    SciTech Connect

    Luo, Jinping; McGinnis, Lynda K.; Carlton, Carol; Beggs, Hilary E.; Kinsey, William H.

    2014-08-01

    Highlights: • PTK2b is expressed in oocytes and is activated following fertilization. • PTK2b suppression in oocytes prevents fertilization, but not parthenogenetic activation. • PTK2b suppression prevents the oocyte from fusing with or incorporating bound sperm. • PTK2b suppressed oocytes that fail to fertilize do not exhibit calcium oscillations. - Abstract: Fertilization triggers rapid changes in intracellular free calcium that serve to activate multiple signaling events critical to the initiation of successful development. Among the pathways downstream of the fertilization-induced calcium transient is the calcium-calmodulin dependent protein tyrosine kinase PTK2b or PYK2 kinase. PTK2b plays an important role in fertilization of the zebrafish oocyte and the objective of the present study was to establish whether PTK2b also functions in mammalian fertilization. PTK2b was activated during the first few hours after fertilization of the mouse oocyte during the period when anaphase resumption was underway and prior to the pronuclear stage. Suppression of PTK2b kinase activity in oocytes blocked sperm incorporation and egg activation although sperm-oocyte binding was not affected. Oocytes that failed to incorporate sperm after inhibitor treatment showed no evidence of a calcium transient and no evidence of anaphase resumption suggesting that egg activation did not occur. The results indicate that PTK2b functions during the sperm-egg fusion process or during the physical incorporation of sperm into the egg cytoplasm and is therefore critical for successful development.

  6. Recommended reference figures for geophysics and geodesy

    NASA Technical Reports Server (NTRS)

    Khan, M. A.; Okeefe, J. A.

    1973-01-01

    Specific reference figures are recommended for consistent use in geophysics and geodesy. The selection of appropriate reference figure for geophysical studies suggests a relationship between the Antarctic negative gravity anomaly and the great shrinkage of the Antarctic ice cap about 4-5 million years ago. The depression of the south polar regions relative to the north polar regions makes the Southern Hemisphere flatter than the Northern Hemisphere, thus producing the third harmonic (pear-shaped) contribution to the earth's figure.

  7. Multiple independent molecular etiology for limb-girdle muscular dystrophy type 2A patients from various geographical origins.

    PubMed Central

    Richard, I; Brenguier, L; Dinçer, P; Roudaut, C; Bady, B; Burgunder, J M; Chemaly, R; Garcia, C A; Halaby, G; Jackson, C E; Kurnit, D M; Lefranc, G; Legum, C; Loiselet, J; Merlini, L; Nivelon-Chevallier, A; Ollagnon-Roman, E; Restagno, G; Topaloglu, H; Beckmann, J S

    1997-01-01

    Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of the segregation of markers flanking the LGMD2A locus and a search for CANP3 mutations were performed for 21 LGMD2 pedigrees from various origins. In addition to the 16 mutations described previously, we report 19 novel mutations. These data indicate that muscular dystrophy caused by mutations in CANP3 are found in patients from all countries examined so far and further support the wide heterogeneity of molecular defects in this rare disease. Images Figure 2a Figure 2b PMID:9150160

  8. Knockdown of the sodium-dependent phosphate co-transporter 2b (NPT2b) suppresses lung tumorigenesis.

    PubMed

    Hong, Seong-Ho; Minai-Tehrani, Arash; Chang, Seung-Hee; Jiang, Hu-Lin; Lee, Somin; Lee, Ah-Young; Seo, Hwi Won; Chae, Chanhee; Beck, George R; Cho, Myung-Haing

    2013-01-01

    The sodium-dependent phosphate co-transporter 2b (NPT2b) plays an important role in maintaining phosphate homeostasis. In previous studies, we have shown that high dietary inorganic phosphate (Pi) consumption in mice stimulated lung tumorigenesis and increased NPT2b expression. NPT2b has also been found to be highly expressed in human lung cancer tissues. The association of high expression of NPT2b in the lung with poor prognosis in oncogenic lung diseases prompted us to test whether knockdown of NPT2b may regulate lung cancer growth. To address this issue, aerosols that contained small interfering RNA (siRNA) directed against NPT2b (siNPT2b) were delivered into the lungs of K-ras (LA1) mice, which constitute a murine model reflecting human lung cancer. Our results clearly showed that repeated aerosol delivery of siNPT2b successfully suppressed lung cancer growth and decreased cancer cell proliferation and angiogenesis, while facilitating apoptosis. These results strongly suggest that NPT2b plays a role lung tumorigenesis and represents a novel target for lung cancer therapy. PMID:24194864

  9. Preclinical studies on targeted delivery of multiple IFNα2b to HLA-DR in diverse hematologic cancers.

    PubMed

    Rossi, Edmund A; Rossi, Diane L; Cardillo, Thomas M; Stein, Rhona; Goldenberg, David M; Chang, Chien-Hsing

    2011-08-18

    The short circulating half-life and side effects of IFNα affect its dosing schedule and efficacy. Fusion of IFNα to a tumor-targeting mAb (mAb-IFNα) can enhance potency because of increased tumor localization and improved pharmacokinetics. We used the Dock-and-Lock method to generate C2-2b-2b, a mAb-IFNα comprising tetrameric IFNα2b site-specifically linked to hL243 (humanized anti-HLA-DR). In vitro, C2-2b-2b inhibited various B-cell lymphoma leukemia and myeloma cell lines. In most cases, this immunocytokine was more effective than CD20-targeted mAb-IFNα or a mixture comprising the parental mAb and IFNα. Our findings indicate that responsiveness depends on HLA-DR expression/density and sensitivity to IFNα and hL243. C2-2b-2b induced more potent and longer-lasting IFNα signaling compared with nontargeted IFNα. Phosphorylation of STAT1 was more robust and persistent than that of STAT3, which may promote apoptosis. C2-2b-2b efficiently depleted lymphoma and myeloma cells from whole human blood but also exhibited some toxicity to B cells, monocytes, and dendritic cells. C2-2b-2b showed superior efficacy compared with nontargeting mAb-IFNα, peginterferonalfa-2a, or a combination of hL243 and IFNα, using human lymphoma and myeloma xenografts. These results suggest that C2-2b-2b should be useful in the treatment of various hematopoietic malignancies. PMID:21680794

  10. HIPK2 controls cytokinesis and prevents tetraploidization by phosphorylating histone H2B at the midbody.

    PubMed

    Rinaldo, Cinzia; Moncada, Alice; Gradi, Alessandra; Ciuffini, Laura; D'Eliseo, Donatella; Siepi, Francesca; Prodosmo, Andrea; Giorgi, Alessandra; Pierantoni, Giovanna M; Trapasso, Francesco; Guarguaglini, Giulia; Bartolazzi, Armando; Cundari, Enrico; Schininà, M Eugenia; Fusco, Alfredo; Soddu, Silvia

    2012-07-13

    Failure in cytokinesis, the final step in cell division, by generating tetra- and polyploidization promotes chromosomal instability, a hallmark of cancer. Here we show that HIPK2, a kinase involved in cell fate decisions in development and response to stress, controls cytokinesis and prevents tetraploidization through its effects on histone H2B. HIPK2 binds and phosphorylates histone H2B at S14 (H2B-S14(P)), and the two proteins colocalize at the midbody. HIPK2 depletion by targeted gene disruption or RNA interference results in loss of H2B-S14(P) at the midbody, prevention of cell cleavage, and tetra- and polyploidization. In HIPK2 null cells, restoration of wild-type HIPK2 activity or expression of a phosphomimetic H2B-S14D derivative abolishes cytokinesis defects and rescues cell proliferation, showing that H2B-S14(P) is required for a faithful cytokinesis. Overall, our data uncover mechanisms of a critical HIPK2 function in cytokinesis and in the prevention of tetraploidization. PMID:22658722

  11. Multiple endocrine neoplasias type 2B and RET proto-oncogene

    PubMed Central

    2012-01-01

    Multiple Endocrine Neoplasia type 2B (MEN 2B) is an autosomal dominant complex oncologic neurocristopathy including medullary thyroid carcinoma, pheochromocytoma, gastrointestinal disorders, marphanoid face, and mucosal multiple ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN 2B syndrome, and it often appears during the first years of life. RET proto-oncogene germline activating mutations are causative for MEN 2B. The 95% of MEN 2B patients are associated with a point mutation in exon 16 (M918/T). A second point mutation at codon 883 has been found in 2%-3% of MEN 2B cases. RET proto-oncogene is also involved in different neoplastic and not neoplastic neurocristopathies. Other RET mutations cause MEN 2A syndrome, familial medullary thyroid carcinoma, or Hirschsprung's disease. RET gene expression is also involved in Neuroblastoma. The main diagnosis standards are the acetylcholinesterase study of rectal mucosa and the molecular analysis of RET. In our protocol the rectal biopsy is, therefore, the first approach. RET mutation detection offers the possibility to diagnose MEN 2B predisposition at a pre-clinical stage in familial cases, and to perform an early total prophylactic thyroidectomy. The surgical treatment of MEN 2B is total thyroidectomy with cervical limphadenectomy of the central compartment of the neck. When possible, this intervention should be performed with prophylactic aim before 1 year of age in patients with molecular genetic diagnosis. Recent advances into the mechanisms of RET proto-oncogene signaling and pathways of RET signal transduction in the development of MEN 2 and MTC will allow new treatment possibilities. PMID:22429913

  12. The role of literal meaning in figurative language comprehension: evidence from masked priming ERP.

    PubMed

    Weiland, Hanna; Bambini, Valentina; Schumacher, Petra B

    2014-01-01

    The role of literal meaning during the construction of meaning that goes beyond pure literal composition was investigated by combining cross-modal masked priming and ERPs. This experimental design was chosen to compare two conflicting theoretical positions on this topic. The indirect access account claims that literal aspects are processed first, and additional meaning components are computed only if no satisfactory interpretation is reached. In contrast, the direct access approach argues that figurative aspects can be accessed immediately. We presented metaphors (These lawyers are hyenas, Experiment 1a and 1b) and producer-for-product metonymies (The boy read Böll, Experiment 2a and 2b) with and without a prime word that was semantically relevant to the literal meaning of the target word (furry and talented, respectively). In the presentation without priming, metaphors revealed a biphasic N400-Late Positivity pattern, while metonymies showed an N400 only. We interpret the findings within a two-phase language architecture where contextual expectations guide initial access (N400) and precede pragmatic adjustment resulting in reconceptualization (Late Positivity). With masked priming, the N400-difference was reduced for metaphors and vanished for metonymies. This speaks against the direct access view that predicts a facilitating effect for the literal condition only and hence would predict the N400-difference to increase. The results are more consistent with indirect access accounts that argue for facilitation effects for both conditions and consequently for consistent or even smaller N400-amplitude differences. This combined masked priming ERP paradigm therefore yields new insights into the role of literal meaning in the online composition of figurative language. PMID:25136309

  13. The role of literal meaning in figurative language comprehension: evidence from masked priming ERP

    PubMed Central

    Weiland, Hanna; Bambini, Valentina; Schumacher, Petra B.

    2014-01-01

    The role of literal meaning during the construction of meaning that goes beyond pure literal composition was investigated by combining cross-modal masked priming and ERPs. This experimental design was chosen to compare two conflicting theoretical positions on this topic. The indirect access account claims that literal aspects are processed first, and additional meaning components are computed only if no satisfactory interpretation is reached. In contrast, the direct access approach argues that figurative aspects can be accessed immediately. We presented metaphors (These lawyers are hyenas, Experiment 1a and 1b) and producer-for-product metonymies (The boy read Böll, Experiment 2a and 2b) with and without a prime word that was semantically relevant to the literal meaning of the target word (furry and talented, respectively). In the presentation without priming, metaphors revealed a biphasic N400-Late Positivity pattern, while metonymies showed an N400 only. We interpret the findings within a two-phase language architecture where contextual expectations guide initial access (N400) and precede pragmatic adjustment resulting in reconceptualization (Late Positivity). With masked priming, the N400-difference was reduced for metaphors and vanished for metonymies. This speaks against the direct access view that predicts a facilitating effect for the literal condition only and hence would predict the N400-difference to increase. The results are more consistent with indirect access accounts that argue for facilitation effects for both conditions and consequently for consistent or even smaller N400-amplitude differences. This combined masked priming ERP paradigm therefore yields new insights into the role of literal meaning in the online composition of figurative language. PMID:25136309

  14. Increased extrasynaptic GluN2B expression is involved in cognitive impairment after isoflurane anesthesia

    PubMed Central

    LI, LUNXU; LI, ZHENGQIAN; CAO, YIYUN; FAN, DONGSHENG; CHUI, DEHUA; GUO, XIANGYANG

    2016-01-01

    There is increasing concern regarding the postoperative cognitive dysfunction (POCD) in the aging population, and general anesthetics are believed to be involved. Isoflurane exposure induced increased N-methyl-D-aspartic acid receptor (NMDAR) GluN2B subunit expression following anesthesia, which was accompanied by alteration of the cognitive function. However, whether isoflurane affects this expression in different subcellular compartments, and is involved in the development of POCD remains to be elucidated. The aims of the study were to investigate the effects of isoflurane on the expression of the synaptic and extrasynaptic NMDAR subunits, GluN2A and GluN2B, as well as the associated alteration of cognitive function in aged rats. The GluN2B antagonist, Ro25–6981, was given to rats exposed to isoflurane to determine the role of GluN2B in the isoflurane-induced alteration of cognitive function. The results showed that spatial learning and memory tested in the Morris water maze (MWM) was impaired at least 7 days after isoflurane exposure, and was returned to control levels 30 days thereafter. Ro25-6981 treatment can alleviate this impairment. Extrasynaptic GluN2B protein expression, but not synaptic GluN2B or GluN2A, increased significantly after isoflurane exposure compared to non-isoflurane exposure, and returned to control levels approximately 30 days thereafter. The results of the present study indicated that isoflurane induced the prolonged upregulation of extrasynaptic GluN2B expression after anesthesia and is involved in reversible cognitive impairment. PMID:27347033

  15. Novel approach to probe subunit-specific contributions to N-methyl-D-aspartate (NMDA) receptor trafficking reveals a dominant role for NR2B in receptor recycling.

    PubMed

    Tang, Tina Tze-Tsang; Badger, John D; Roche, Paul A; Roche, Katherine W

    2010-07-01

    N-Methyl-d-aspartate (NMDA) receptors are expressed at excitatory synapses throughout the brain and are essential for neuronal development and synaptic plasticity. Functional NMDA receptors are tetramers, typically composed of NR1 and NR2 subunits (NR2A-D). NR2A and NR2B are expressed in the forebrain and are thought to assemble as diheteromers (NR1/NR2A, NR1/NR2B) and triheteromers (NR1/NR2A/NR2B). NR2A and NR2B contain cytosolic domains that regulate distinct postendocytic sorting events, with NR2A sorting predominantly into the degradation pathway, and NR2B preferentially trafficking through the recycling pathway. However, the interplay between these two subunits remains an open question. We have now developed a novel approach based on the dimeric feature of the alpha- and beta-chains of the human major histocompatibility complex class II molecule. We created chimeras of alpha- and beta-chains with the NR2A and NR2B C termini and evaluated endocytosis of dimers. Like chimeric proteins containing only a single NR2A or NR2B C-terminal domain, major histocompatibility complex class II-NR2A homodimers sort predominantly to late endosomes, whereas NR2B homodimers traffic to recycling endosomes. Interestingly, NR2A/NR2B heterodimers traffic preferentially through the recycling pathway, and NR2B is dominant in regulating dimer trafficking in both heterologous cells and neurons. In addition, the recycling of NR2B-containing NMDARs in wild-type neurons is not significantly different from NR2A(-/-) neurons. These data support a dominant role for NR2B in regulating the trafficking of triheteromeric NMDARs in vivo. Furthermore, our molecular approach allows for the direct and selective evaluation of dimeric assemblies and can be used to define dominant trafficking domains in other multisubunit protein complexes. PMID:20427279

  16. "Blessed": Musical Talent, Smartness, & Figured Identities

    ERIC Educational Resources Information Center

    Hoffman, Adria R.

    2015-01-01

    The purpose of this study is to explore smartness and talent as social constructs. Drawing on Holland et al.'s (1998) figured identities, this article explores the figuring of abilities by elucidating the voices of African American high school chorus students. Critical Race Theory (CRT) helps to unpack normalized language and practices that…

  17. Evolution of the Significant Figure Rules

    ERIC Educational Resources Information Center

    Carter, Ashley R.

    2013-01-01

    Today, almost all introductory physics textbooks include standardized "rules" on how to find the number of significant figures in a calculated value. And yet, 30 years ago these rules were almost nonexistent. Why have we increased the role of significant figures in introductory classes, and should we continue this trend? A look back at…

  18. Plasma surface figuring of large optical components

    NASA Astrophysics Data System (ADS)

    Jourdain, R.; Castelli, M.; Morantz, P.; Shore, P.

    2012-04-01

    Fast figuring of large optical components is well known as a highly challenging manufacturing issue. Different manufacturing technologies including: magnetorheological finishing, loose abrasive polishing, ion beam figuring are presently employed. Yet, these technologies are slow and lead to expensive optics. This explains why plasma-based processes operating at atmospheric pressure have been researched as a cost effective means for figure correction of metre scale optical surfaces. In this paper, fast figure correction of a large optical surface is reported using the Reactive Atom Plasma (RAP) process. Achievements are shown following the scaling-up of the RAP figuring process to a 400 mm diameter area of a substrate made of Corning ULE®. The pre-processing spherical surface is characterized by a 3 metres radius of curvature, 2.3 μm PVr (373nm RMS), and 1.2 nm Sq nanometre roughness. The nanometre scale correction figuring system used for this research work is named the HELIOS 1200, and it is equipped with a unique plasma torch which is driven by a dedicated tool path algorithm. Topography map measurements were carried out using a vertical work station instrumented by a Zygo DynaFiz interferometer. Figuring results, together with the processing times, convergence levels and number of iterations, are reported. The results illustrate the significant potential and advantage of plasma processing for figuring correction of large silicon based optical components.

  19. Figure-Associated Text Summarization and Evaluation

    PubMed Central

    Polepalli Ramesh, Balaji; Sethi, Ricky J.; Yu, Hong

    2015-01-01

    Biomedical literature incorporates millions of figures, which are a rich and important knowledge resource for biomedical researchers. Scientists need access to the figures and the knowledge they represent in order to validate research findings and to generate new hypotheses. By themselves, these figures are nearly always incomprehensible to both humans and machines and their associated texts are therefore essential for full comprehension. The associated text of a figure, however, is scattered throughout its full-text article and contains redundant information content. In this paper, we report the continued development and evaluation of several figure summarization systems, the FigSum+ systems, that automatically identify associated texts, remove redundant information, and generate a text summary for every figure in an article. Using a set of 94 annotated figures selected from 19 different journals, we conducted an intrinsic evaluation of FigSum+. We evaluate the performance by precision, recall, F1, and ROUGE scores. The best FigSum+ system is based on an unsupervised method, achieving F1 score of 0.66 and ROUGE-1 score of 0.97. The annotated data is available at figshare.com (http://figshare.com/articles/Figure_Associated_Text_Summarization_and_Evaluation/858903). PMID:25643357

  20. Feature Assignment in Perception of Auditory Figure

    ERIC Educational Resources Information Center

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory…

  1. Figuring "Success" in a Bilingual High School

    ERIC Educational Resources Information Center

    Michael, Ali; Andrade, Norma; Bartlett, Lesley

    2007-01-01

    Using the concept of figured worlds, this article demonstrates how the faculty, staff, and students of Gregorio Luperon High School in New York City figured "success" by prioritizing the students' linguistic and cultural resources. "Success" was constructed specifically through granting Spanish high status, developing positive teacher-student…

  2. Automatic figure classification in bioscience literature.

    PubMed

    Kim, Daehyun; Ramesh, Balaji Polepalli; Yu, Hong

    2011-10-01

    Millions of figures appear in biomedical articles, and it is important to develop an intelligent figure search engine to return relevant figures based on user entries. In this study we report a figure classifier that automatically classifies biomedical figures into five predefined figure types: Gel-image, Image-of-thing, Graph, Model, and Mix. The classifier explored rich image features and integrated them with text features. We performed feature selection and explored different classification models, including a rule-based figure classifier, a supervised machine-learning classifier, and a multi-model classifier, the latter of which integrated the first two classifiers. Our results show that feature selection improved figure classification and the novel image features we explored were the best among image features that we have examined. Our results also show that integrating text and image features achieved better performance than using either of them individually. The best system is a multi-model classifier which combines the rule-based hierarchical classifier and a support vector machine (SVM) based classifier, achieving a 76.7% F1-score for five-type classification. We demonstrated our system at http://figureclassification.askhermes.org/. PMID:21645638

  3. The Development of Ambiguous Figure Perception

    ERIC Educational Resources Information Center

    Wimmer, Marina C.; Doherty, Martin J.

    2011-01-01

    Ambiguous figures have fascinated researchers for almost 200 years. The physical properties of these figures remain constant, yet two distinct interpretations are possible; these reverse (switch) from one percept to the other. The consensus is that reversal requires complex interaction of perceptual bottom-up and cognitive top-down elements. The…

  4. Human Figure Drawings: Abusing the Abused.

    ERIC Educational Resources Information Center

    Bardos, Achilles N.

    1993-01-01

    Responds to previous article (Motta, Little, and Tobin, this issue) which reviewed data-based studies on figure drawings and found little support for their validity or use in assessing personality, behavior, emotion, or intellectual functioning. Notes recent approaches to interpretation of human figure drawings and cites flaws in argument against…

  5. Figure-associated text summarization and evaluation.

    PubMed

    Polepalli Ramesh, Balaji; Sethi, Ricky J; Yu, Hong

    2015-01-01

    Biomedical literature incorporates millions of figures, which are a rich and important knowledge resource for biomedical researchers. Scientists need access to the figures and the knowledge they represent in order to validate research findings and to generate new hypotheses. By themselves, these figures are nearly always incomprehensible to both humans and machines and their associated texts are therefore essential for full comprehension. The associated text of a figure, however, is scattered throughout its full-text article and contains redundant information content. In this paper, we report the continued development and evaluation of several figure summarization systems, the FigSum+ systems, that automatically identify associated texts, remove redundant information, and generate a text summary for every figure in an article. Using a set of 94 annotated figures selected from 19 different journals, we conducted an intrinsic evaluation of FigSum+. We evaluate the performance by precision, recall, F1, and ROUGE scores. The best FigSum+ system is based on an unsupervised method, achieving F1 score of 0.66 and ROUGE-1 score of 0.97. The annotated data is available at figshare.com (http://figshare.com/articles/Figure_Associated_Text_Summarization_and_Evaluation/858903). PMID:25643357

  6. Detector array evaluation and figures of merit

    NASA Technical Reports Server (NTRS)

    Dereniak, Eustace L.

    1990-01-01

    The commonly used methods to evaluate the performance of a two-dimensional focal-plane array using charge transfer devices are reviewed. Two figures of merit that attempt to combine quantum efficiency, read noise and dark-current generation into a single parameter are discussed. The figures of merit are suggested as possible alternatives to the D asterisk.

  7. Aspects of Reference in Figurative Language.

    ERIC Educational Resources Information Center

    Pankhurst, Anne

    1995-01-01

    This study considers some problems of reference found in figurative language, particularly in metaphor and metonymy. Analysis is based on the notion that the effects communicated by figurative language depend to a large extent on reference to more than one concept, experience, or entity, and that the presence of multiple potential referents…

  8. Equilibrium figures in geodesy and geophysics.

    NASA Astrophysics Data System (ADS)

    Moritz, H.

    There is an enormous literature on geodetic equilibrium figures, but the various works have not always been interrelated, also for linguistic reasons (English, French, German, Italian, Russian). The author attempts to systematize the various approaches and to use the standard second-order theory for a study of the deviation of the actual earth and of the equipotential reference ellipsoid from an equilibrium figure.

  9. 46 CFR 69.123 - Figures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Figures. 69.123 Section 69.123 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DOCUMENTATION AND MEASUREMENT OF VESSELS MEASUREMENT OF VESSELS Standard Measurement System § 69.123 Figures. EC01FE91.042 EC01FE91.043 EC01FE91.044...

  10. In silico analysis of Brucella abortus Omp2b and in vitro expression of SOmp2b

    PubMed Central

    2016-01-01

    Purpose At present, there is no vaccine available for the prevention of human brucellosis. Brucella outer membrane protein 2b (Omp2b) is a 36 kD porin existed in common Brucella pathogens and it is considered as priority antigen for designing a new subunit vaccine. Materials and Methods In the current study, we aimed to predict and analyze the secondary and tertiary structures of the Brucella abortus Omp2b protein, and to predict T-cell and B-cell epitopes with the help of bioinformatics tools. Subsequently, cloning and expression of the short form of Omp2b (SOmp2b) was performed using pET28a expression vector and Escherichia coli BL21 host, respectively. The recombinant SOmp2b (rSOmp2b) was purified with Ni-NTA column. Results The recombinant protein was successfully expressed in E. coli host and purified under denaturation conditions. The yield of the purified rSOmp2b was estimated by Bradford method and found to be 220 µg/mL of the culture. Conclusion Our results indicate that Omp2b protein has a potential to induce both B-cell– and T-cell–mediated immune responses and it can be evaluated as a new subunit vaccine candidate against brucellosis. PMID:26866027

  11. Building Customized University-to-Business (U2B) Partnerships

    ERIC Educational Resources Information Center

    Irvine, George; Verma, Lisa

    2013-01-01

    Continuing education (CE) units throughout the United States have successfully built University-to-Business (U2B) partnerships to provide greater value to their community partners and to increase revenue for the university. Our experience in building U2B partnerships and feedback from our partners--businesses, corporations, state agencies, and…

  12. Role of adenosine A2B receptors in inflammation

    PubMed Central

    Feoktistov, Igor; Biaggioni, Italo

    2013-01-01

    Recent progress in our understanding of the unique role of A2B receptors in the regulation of inflammation, immunity and tissue repair was considerably facilitated with the introduction of new pharmacological and genetic tools. However, it also led to seemingly conflicting conclusions on the role of A2B adenosine receptors in inflammation with some publications indicating pro-inflammatory effects and others suggesting the opposite. This chapter reviews the functions of A2B receptors in various cell types related to inflammation and integrated effects of A2B receptor modulation in several animal models of inflammation. It is argued that translation of current findings into novel therapies would require a better understanding of A2B receptors functions in diverse types of inflammatory responses in various tissues and at different points of their progression. PMID:21586358

  13. Importance of the GluN2B Carboxy-Terminal Domain for Enhancement of Social Memories

    ERIC Educational Resources Information Center

    Jacobs, Stephanie; Wei, Wei; Wang, Deheng; Tsien, Joe Z.

    2015-01-01

    The N-methyl-D-aspartate (NMDA) receptor is known to be necessary for many forms of learning and memory, including social recognition memory. Additionally, the GluN2 subunits are known to modulate multiple forms of memory, with a high GluN2A:GluN2B ratio leading to impairments in long-term memory, while a low GluN2A:GluN2B ratio enhances some…

  14. 16 CFR Figure 3 to Part 1509 - Figure 3 to Part 1509

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 3 to Part 1509 3 Figure 3 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 3 Figure 3 to Part 1509 EC03OC91.066...

  15. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  16. 16 CFR Figure 1 to Part 1509 - Figure 1 to Part 1509

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 1 to Part 1509 1 Figure 1 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 1 Figure 1 to Part 1509 EC03OC91.064...

  17. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 3 Figure 3 to Part 1508 EC03OC91.063...

  18. 16 CFR Figure 1 to Part 1509 - Figure 1 to Part 1509

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 1 to Part 1509 1 Figure 1 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 1 Figure 1 to Part 1509 EC03OC91.064...

  19. 16 CFR Figure 3 to Part 1509 - Figure 3 to Part 1509

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 3 to Part 1509 3 Figure 3 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 3 Figure 3 to Part 1509 EC03OC91.066...

  20. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 3 Figure 3 to Part 1508 EC03OC91.063...

  1. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  2. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  3. Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

    PubMed Central

    Montellier, Emilie; Boussouar, Fayçal; Rousseaux, Sophie; Zhang, Kai; Buchou, Thierry; Fenaille, François; Shiota, Hitoshi; Debernardi, Alexandra; Héry, Patrick; Curtet, Sandrine; Jamshidikia, Mahya; Barral, Sophie; Holota, Hélène; Bergon, Aurélie; Lopez, Fabrice; Guardiola, Philippe; Pernet, Karin; Imbert, Jean; Petosa, Carlo; Tan, Minjia; Zhao, Yingming; Gérard, Matthieu; Khochbin, Saadi

    2013-01-01

    The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg. PMID:23884607

  4. New halogenated tris-(phenylalkyl)amines as h5-HT2B receptor ligands.

    PubMed

    Kapadia, Nirav; Ahmed, Shahrear; Harding, Wayne W

    2016-07-15

    A series of compounds in which various halogen substituents were incorporated into a phenyl ring of a tris-(phenylalkyl)amine scaffold, was synthesized and evaluated for affinity to h5-HT2 receptors. In general, all compounds were found to have good affinity for the 5-HT2B receptor and were selective over 5-HT2A and 5-HT2C receptors. Compound 9i was the most selective compound in this study and is the highest affinity 5-HT2B receptor ligand bearing a tris-(phenylalkyl)amine scaffold to date. PMID:27261181

  5. 5-HT2B Receptor Antagonists Inhibit Fibrosis and Protect from RV Heart Failure

    PubMed Central

    Janssen, Wiebke; Schymura, Yves; Novoyatleva, Tatyana; Luitel, Himal; Tretyn, Aleksandra; Pullamsetti, Soni Savai; Weissmann, Norbert; Seeger, Werner; Ghofrani, Hossein Ardeschir; Schermuly, Ralph Theo

    2015-01-01

    Objective. The serotonin (5-HT) pathway was shown to play a role in pulmonary hypertension (PH), but its functions in right ventricular failure (RVF) remain poorly understood. The aim of the current study was to investigate the effects of Terguride (5-HT2A and 2B receptor antagonist) or SB204741 (5-HT2B receptor antagonist) on right heart function and structure upon pulmonary artery banding (PAB) in mice. Methods. Seven days after PAB, mice were treated for 14 days with Terguride (0.2 mg/kg bid) or SB204741 (5 mg/kg day). Right heart function and remodeling were assessed by right heart catheterization, magnetic resonance imaging (MRI), and histomorphometric methods. Total secreted collagen content was determined in mouse cardiac fibroblasts isolated from RV tissues. Results. Chronic treatment with Terguride or SB204741 reduced right ventricular fibrosis and showed improved heart function in mice after PAB. Moreover, 5-HT2B receptor antagonists diminished TGF-beta1 induced collagen synthesis of RV cardiac fibroblasts in vitro. Conclusion. 5-HT2B receptor antagonists reduce collagen deposition, thereby inhibiting right ventricular fibrosis. Chronic treatment prevented the development and progression of pressure overload-induced RVF in mice. Thus, 5-HT2B receptor antagonists represent a valuable novel therapeutic approach for RVF. PMID:25667920

  6. Characterization of CYP2B6 in a CYP2B6-Humanized Mouse Model: Inducibility in the Liver by Phenobarbital and Dexamethasone and Role in Nicotine Metabolism In Vivo

    PubMed Central

    Liu, Zhihua; Li, Lei; Wu, Hong; Hu, Jing; Ma, Jun; Zhang, Qing-Yu

    2015-01-01

    The aim of this study was to further characterize the expression and function of human CYP2B6 in a recently generated CYP2A13/2B6/2F1-transgenic (TG) mouse model, in which CYP2B6 is expressed selectively in the liver. The inducibility of CYP2B6 by phenobarbital (PB) and dexamethasone (DEX), known inducers of CYP2B6 in human liver, was examined in the TG mice, as well as in TG/Cyp2abfgs-null (or “CYP2B6-humanized”) mice. Hepatic expression of CYP2B6 mRNA and protein was greatly induced by PB or DEX treatment in both TG and TG/Cyp2abfgs-null mice. Function of the transgenic CYP2B6 was first studied using bupropion as a probe substrate. In PB-treated mice, the rates of hepatic microsomal hydroxybupropion formation (at 50 μM bupropion) were >4-fold higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice (for both male and female mice); the rate difference was accompanied by a 5-fold higher catalytic efficiency in the TG/Cyp2abfgs-null mice and was abolished by an antibody to CYP2B6. The ability of CYP2B6 to metabolize nicotine was then examined, both in vitro and in vivo. The rates of hepatic microsomal cotinine formation from nicotine were significantly higher in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice, pretreated with PB or DEX. Furthermore, systemic nicotine metabolism was faster in TG/Cyp2abfgs-null than in Cyp2abfgs-null mice. Thus, the transgenic CYP2B6 was inducible and functional, and, in the absence of mouse CYP2A and CYP2B enzymes, it contributed to nicotine metabolism in vivo. The CYP2B6-humanized mouse will be valuable for studies on in vivo roles of hepatic CYP2B6 in xenobiotic metabolism and toxicity. PMID:25409894

  7. Comprehension of Figurative Language in Youth.

    ERIC Educational Resources Information Center

    Nippold, Marilyn A.

    1985-01-01

    A review of developmental studies concerning metaphor, idiom, and proverb comprehension suggest a variety of assessment tasks for language impaired children. Also suggested are such intervention considerations as the comprehension of literal meaning of figurative expressions before nonliteral meanings. (CL)

  8. Significant Figure Rules for General Arithmetic Functions.

    ERIC Educational Resources Information Center

    Graham, D. M.

    1989-01-01

    Provides some significant figure rules used in chemistry including the general theoretical basis; logarithms and antilogarithms; exponentiation (with exactly known exponents); sines and cosines; and the extreme value rule. (YP)

  9. Setdb1 histone methyltransferase regulates mood-related behaviors and expression of the NMDA receptor subunit NR2B.

    PubMed

    Jiang, Yan; Jakovcevski, Mira; Bharadwaj, Rahul; Connor, Caroline; Schroeder, Frederick A; Lin, Cong L; Straubhaar, Juerg; Martin, Gilles; Akbarian, Schahram

    2010-05-26

    Histone methyltransferases specific for the histone H3-lysine 9 residue, including Setdb1 (Set domain, bifurcated 1)/Eset/Kmt1e are associated with repressive chromatin remodeling and expressed in adult brain, but potential effects on neuronal function and behavior remain unexplored. Here, we report that transgenic mice with increased Setdb1 expression in adult forebrain neurons show antidepressant-like phenotypes in behavioral paradigms for anhedonia, despair, and learned helplessness. Chromatin immunoprecipitation in conjunction with DNA tiling arrays (ChIP-chip) revealed that genomic occupancies of neuronal Setdb1 are limited to <1% of annotated genes, which include the NMDA receptor subunit NR2B/Grin2B and other ionotropic glutamate receptor genes. Chromatin conformation capture and Setdb1-ChIP revealed a loop formation tethering the NR2B/Grin2b promoter to the Setdb1 target site positioned 30 kb downstream of the transcription start site. In hippocampus and ventral striatum, two key structures in the neuronal circuitry regulating mood-related behaviors, Setdb1-mediated repressive histone methylation at NR2B/Grin2b was associated with decreased NR2B expression and EPSP insensitivity to pharmacological blockade of NR2B, and accelerated NMDA receptor desensitization consistent with a shift in NR2A/B subunit ratios. In wild-type mice, systemic treatment with the NR2B antagonist, Ro25-6981 [R-(R,S)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine propranol], and hippocampal small interfering RNA-mediated NR2B/Grin2b knockdown resulted in behavioral changes similar to those elicited by the Setdb1 transgene. Together, these findings point to a role for neuronal Setdb1 in the regulation of affective and motivational behaviors through repressive chromatin remodeling at a select set of target genes, resulting in altered NMDA receptor subunit composition and other molecular adaptations. PMID:20505083

  10. Ion beam figuring system in NUDT

    NASA Astrophysics Data System (ADS)

    Zhou, Lin; Xie, Xuhui; Dai, Yifan; Jiao, Changjun; Li, Shengyi

    2007-12-01

    Ion beam figuring (IBF) is an optical fabrication technique that provides highly deterministic process to correct surface figure error of previously polished surfaces by using a directed, inert and neutralized ion beam to physically sputter material from the optic surface. Recently, an ion beam figuring system KDIFS-500 has been designed and built in National University of Defense Technology (NUDT) of the P.R. China. KDIFS-500 is capable of processing workpiece up to Φ500mm. Line scanning process was discussed in detail for estimating the parameters of the beam removal function (BRF) in process. Experiments were conducted to demonstrate that the BRF increases gradually in process and by employing a stability control, the BRF can be kept stable in process. Finally, a Φ95 mm plano optical sample of CVD coated SiC substrate has been figured in two process iterations for demonstrating the correction capability of the KDIFS-500. Their figure convergence ratios reached 5.8 and 2.1 respectively. The actual figure residual errors were basically consistent with the predicted error. These consistencies indicated that the IBF processes on KDIFS-500 are predictable deterministic processes.

  11. Ion beam figuring of small optical components

    NASA Astrophysics Data System (ADS)

    Drueding, Thomas W.; Fawcett, Steven C.; Wilson, Scott R.; Bifano, Thomas G.

    1995-12-01

    Ion beam figuring provides a highly deterministic method for the final precision figuring of optical components with advantages over conventional methods. The process involves bombarding a component with a stable beam of accelerated particles that selectively removes material from the surface. Figure corrections are achieved by rastering the fixed-current beam across the workplace at appropriate, time-varying velocities. Unlike conventional methods, ion figuring is a noncontact technique and thus avoids such problems as edge rolloff effects, tool wear, and force loading of the workpiece. This work is directed toward the development of the precision ion machining system at NASA's Marshall Space Flight Center. This system is designed for processing small (approximately equals 10-cm diam) optical components. Initial experiments were successful in figuring 8-cm-diam fused silica and chemical-vapor-deposited SiC samples. The experiments, procedures, and results of figuring the sample workpieces to shallow spherical, parabolic (concave and convex), and non-axially-symmetric shapes are discussed. Several difficulties and limitations encountered with the current system are discussed. The use of a 1-cm aperture for making finer corrections on optical components is also reported.

  12. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  13. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  14. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits Formulas and Authorized Uses § 21.33 Formula No. 2-B....

  15. Npt2b Deletion Attenuates Hyperphosphatemia Associated with CKD

    PubMed Central

    Tang, Wen; Bracken, Christina; O’Brien, Stephen P.; Song, Wenping; Boulanger, Joseph; Ryan, Susan; Phillips, Lucy; Liu, Shiguang; Arbeeny, Cynthia; Ledbetter, Steven; Sabbagh, Yves

    2012-01-01

    The incidence of cardiovascular events and mortality strongly correlates with serum phosphate in individuals with CKD. The Npt2b transporter contributes to maintaining phosphate homeostasis in the setting of normal renal function, but its role in CKD-associated hyperphosphatemia is not well understood. Here, we used adenine to induce uremia in both Npt2b-deficient and wild-type mice. Compared with wild-type uremic mice, Npt2b-deficient uremic mice had significantly lower levels of serum phosphate and attenuation of FGF23. Treating Npt2b-deficient mice with the phosphate binder sevelamer carbonate further reduced serum phosphate levels. Uremic mice exhibited high turnover renal osteodystrophy; treatment with sevelamer significantly decreased the number of osteoclasts and the rate of mineral apposition in Npt2b-deficient mice, but sevelamer did not affect bone formation and rate of mineral apposition in wild-type mice. Taken together, these data suggest that targeting Npt2b in addition to using dietary phosphorus binders may be a therapeutic approach to modulate serum phosphate in CKD. PMID:22859851

  16. Independent Review of AFC 2A, 2B, and 2E ATR Irradiation Tests

    SciTech Connect

    M. Cappiello; R. Hobbins; K. Penny; L. Walters

    2014-01-01

    As part of the Department of Energy Advanced Fuel Cycle program, a series of fuels development irradiation tests have been performed in the Advanced Test Reactor (ATR) at the Idaho National Laboratory. These tests are providing excellent data for advanced fuels development. The program is focused on the transmutation of higher actinides which best can be accomplished in a sodium-cooled fast reactor. Because a fast test reactor is no longer available in the US, a special test vehicle is used to achieve near-prototypic fast reactor conditions (neutron spectra and temperature) for use in ATR (a water-cooled thermal reactor). As part of the testing program, there were many successful tests of advanced fuels including metals and ceramics. Recently however, there have been three experimental campaigns using metal fuels that experienced failure during irradiation. At the request of the program, an independent review committee was convened to review the post-test analyses performed by the fuels development team, to assess the conclusions of the team for the cause of the failures, to assess the adequacy and completeness of the analyses, to identify issues that were missed, and to make recommendations for improvements in the design and operation of future tests. Although there is some difference of opinion, the review committee largely agreed with the conclusions of the fuel development team regarding the cause of the failures. For the most part, the analyses that support the conclusions are sufficient.

  17. A Highly Conserved Region within H2B Is Important for FACT To Act on Nucleosomes

    PubMed Central

    Zheng, Suting; Crickard, J. Brooks; Srikanth, Abhinaya

    2014-01-01

    Histone N-terminal tails play crucial roles in chromatin-related processes. The tails of histones H3 and H4 are highly conserved and well characterized, but much less is known about the functions of the tails of histones H2A and H2B and their sequences are more divergent among eukaryotes. Here we characterized the function of the only highly conserved region in the H2B tail, the H2B repression (HBR) domain. Once thought to play a role only in repression, it also has an uncharacterized function in gene activation and DNA damage responses. We report that deletion of the HBR domain impairs the eviction of nucleosomes at the promoters and open reading frames of genes. A closer examination of the HBR domain mutants revealed that they displayed phenotypes similar to those of histone chaperone complex FACT mutants, including an increase in intragenic transcription and the accumulation of free histones in cells. Biochemical characterization of recombinant nucleosomes indicates that deletion of the HBR domain impairs FACT-dependent removal of H2A-H2B from nucleosomes, suggesting that the HBR domain plays an important role in allowing FACT to disrupt dimer-DNA interactions. We have uncovered a previously unappreciated role for the HBR domain in regulating chromatin structure and have provided insight into how FACT acts on nucleosomes. PMID:24248595

  18. Acousto-optic interaction in alpha-BaB(2)O(4)and Li(2)B(4)O(7) crystals.

    PubMed

    Martynyuk-Lototska, Irina; Mys, Oksana; Dudok, Taras; Adamiv, Volodymyr; Smirnov, Yevgen; Vlokh, Rostyslav

    2008-07-01

    Experimental studies and analysis of acousto-optic diffraction in alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are given. Ultrasonic wave velocity, elastic compliance and stiffness coefficients, and piezo-optic and photoelastic coefficients of alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals are determined. The acousto-optic figure of merit has been estimated for different possible geometries of acousto-optic interaction. It is shown that the acousto-optic figures of merit for alpha-BaB(2)O(4) crystals reach the value M(2)=(270 +/- 70) x 10(-15) s(3)/kg for the case of interaction with the slowest ultrasonic wave. The directions of propagation and polarization of those acoustic waves are obtained on the basis of construction of acoustic slowness surfaces. The acousto-optic diffraction is experimentally studied for alpha-BaB(2)O(4) and Li(2)B(4)O(7) crystals. PMID:18594591

  19. Recent improvements in the development of A2B adenosine receptor agonists

    PubMed Central

    Tabrizi, Mojgan Aghazadeh; Fruttarolo, Francesca; Romagnoli, Romeo; Preti, Delia

    2009-01-01

    Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary

  20. Recent improvements in the development of A2B adenosine receptor agonists

    PubMed Central

    Tabrizi, Mojgan Aghazadeh; Fruttarolo, Francesca; Romagnoli, Romeo; Preti, Delia

    2008-01-01

    Adenosine is known to exert most of its physiological functions by acting as local modulator at four receptor subtypes named A1, A2A, A2B and A3 (ARs). Principally as a result of the difficulty in identifying potent and selective agonists, the A2B AR is the least extensively characterised of the adenosine receptors family. Despite these limitations, growing understanding of the physiological meaning of this target indicates promising therapeutic perspectives for specific ligands. As A2B AR signalling seems to be associated with pre/postconditioning cardioprotective and anti-inflammatory mechanisms, selective agonists may represent a new therapeutic group for patients suffering from coronary artery disease. Herein we present an overview of the recent advancements in identifying potent and selective A2B AR agonists reported in scientific and patent literature. These compounds can be classified into adenosine-like and nonadenosine ligands. Nucleoside-based agonists are the result of modifying adenosine by substitution at the N6-, C2-positions of the purine heterocycle and/or at the 5′-position of the ribose moiety or combinations of these substitutions. Compounds 1-deoxy-1-{6-[N′-(furan-2-carbonyl)-hydrazino]-9H-purin-9-yl}-N-ethyl-β-D-ribofuranuronamide (19, hA1Ki = 1050 nM, hA2AKi = 1550 nM, hA2B EC50 = 82 nM, hA3Ki > 5 μM) and its 2-chloro analogue 23 (hA1Ki = 3500 nM, hA2AKi = 4950 nM, hA2B EC50 = 210 nM, hA3Ki > 5 μM) were confirmed to be potent and selective full agonists in a cyclic adenosine monophosphate (cAMP) functional assay in Chinese hamster ovary (CHO) cells expressing hA2B AR. Nonribose ligands are represented by conveniently substituted dicarbonitrilepyridines, among which 2-[6-amino-3,5-dicyano-4-[4-(cyclopropylmethoxy)phenyl]pyridin-2-ylsulfanyl]acetamide (BAY-60–6583, hA1, hA2A, hA3 EC50 > 10 μM; hA2B EC50 = 3 nM) is currently under preclinical-phase investigation for treating coronary

  1. Wet-Etch Figuring Optical Figuring by Controlled Application of Liquid Etchant

    SciTech Connect

    Britten, J

    2001-02-13

    WET-ETCH FIGURING (WEF) is an automated method of precisely figuring optical materials by the controlled application of aqueous etchant solution. This technology uses surface-tension-gradient-driven flow to confine and stabilize a wetted zone of an etchant solution or other aqueous processing fluid on the surface of an object. This wetted zone can be translated on the surface in a computer-controlled fashion for precise spatial control of the surface reactions occurring (e.g. chemical etching). WEF is particularly suitable for figuring very thin optical materials because it applies no thermal or mechanical stress to the material. Also, because the process is stress-free the workpiece can be monitored during figuring using interferometric metrology, and the measurements obtained can be used to control the figuring process in real-time--something that cannot be done with traditional figuring methods.

  2. Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance

    PubMed Central

    Zanger, Ulrich M.; Klein, Kathrin

    2013-01-01

    Cytochrome P450 2B6 (CYP2B6) belongs to the minor drug metabolizing P450s in human liver. Expression is highly variable both between individuals and within individuals, owing to non-genetic factors, genetic polymorphisms, inducibility, and irreversible inhibition by many compounds. Drugs metabolized mainly by CYP2B6 include artemisinin, bupropion, cyclophosphamide, efavirenz, ketamine, and methadone. CYP2B6 is one of the most polymorphic CYP genes in humans and variants have been shown to affect transcriptional regulation, splicing, mRNA and protein expression, and catalytic activity. Some variants appear to affect several functional levels simultaneously, thus, combined in haplotypes, leading to complex interactions between substrate-dependent and -independent mechanisms. The most common functionally deficient allele is CYP2B6*6 [Q172H, K262R], which occurs at frequencies of 15 to over 60% in different populations. The allele leads to lower expression in liver due to erroneous splicing. Recent investigations suggest that the amino acid changes contribute complex substrate-dependent effects at the activity level, although data from recombinant systems used by different researchers are not well in agreement with each other. Another important variant, CYP2B6*18 [I328T], occurs predominantly in Africans (4–12%) and does not express functional protein. A large number of uncharacterized variants are currently emerging from different ethnicities in the course of the 1000 Genomes Project. The CYP2B6 polymorphism is clinically relevant for HIV-infected patients treated with the reverse transcriptase inhibitor efavirenz, but it is increasingly being recognized for other drug substrates. This review summarizes recent advances on the functional and clinical significance of CYP2B6 and its genetic polymorphism, with particular emphasis on the comparison of kinetic data obtained with different substrates for variants expressed in different recombinant expression systems. PMID

  3. Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b).

    PubMed

    Yu, Qin-Wei; Hu, Jie; Wang, Hao; Chen, Xin; Zhao, Fang; Gao, Peng; Yang, Qiu-Bin; Sun, Dan-Dan; Zhang, Lu-Yong; Yan, Ming

    2016-05-01

    The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases. PMID:27478099

  4. Fibrillin-2b regulates endocardial morphogenesis in zebrafish.

    PubMed

    Mellman, Katharine; Huisken, Jan; Dinsmore, Colin; Hoppe, Cornelia; Stainier, Didier Y

    2012-12-01

    scotch tape (sco) is a zebrafish cardiac mutant initially proposed to exhibit a reduced amount of cardiac jelly, the extracellular matrix between the myocardial and endocardial layers. We analyzed sco(te382) mutant hearts in detail using both selective plane illumination microscopy (SPIM) and transmission electron microscopy (TEM), and observed a fascinating endocardial defect. Time-lapse SPIM imaging of wild-type and mutant embryos revealed significant and dynamic gaps between endocardial cells during development. Although these gaps close in wild-type animals, they fail to close in the mutants, ultimately leading to a near complete absence of endocardial cells in the atrial chamber by the heart looping stage. TEM analyses confirm the presence of gaps between endocardial cells in sco mutants, allowing the apparent leakage of cardiac jelly into the lumen. High-resolution mapping places the sco(te382) mutation within the fbn2b locus, which encodes the extracellular matrix protein Fibrillin 2b (OMIM ID: 121050). Complementation and further phenotypic analyses confirm that sco is allelic to puff daddy(gw1) (pfd(gw1)), a null mutant in fbn2b, and that sco(te382) is a hypomorphic allele of fbn2b. fbn2b belongs to a family of genes responsible for the assembly of microfibrils throughout development, and is essential for microfibril structural integrity. In sco(te382) mutants, Fbn2b is disabled by a missense mutation in a highly conserved cbEGF domain, which likely interferes with protein folding. Integrating data obtained from microscopy and molecular biology, we posit that this mutation impacts the rigidity of Fbn2b, imparting a structural defect that weakens endocardial adhesion thereby resulting in perforated endocardium. PMID:22841646

  5. Serotonin 2B Receptor Antagonism Prevents Heritable Pulmonary Arterial Hypertension

    PubMed Central

    Schroer, Alison K.; Chen, Peter; Ryzhova, Larisa M.; Gladson, Santhi; Shay, Sheila; Hutcheson, Joshua D.; Merryman, W. David

    2016-01-01

    Serotonergic anorexigens are the primary pharmacologic risk factor associated with pulmonary arterial hypertension (PAH), and the resulting PAH is clinically indistinguishable from the heritable form of disease, associated with BMPR2 mutations. Both BMPR2 mutation and agonists to the serotonin receptor HTR2B have been shown to cause activation of SRC tyrosine kinase; conversely, antagonists to HTR2B inhibit SRC trafficking and downstream function. To test the hypothesis that a HTR2B antagonist can prevent BMRP2 mutation induced PAH by restricting aberrant SRC trafficking and downstream activity, we exposed BMPR2 mutant mice, which spontaneously develop PAH, to a HTR2B antagonist, SB204741, to block the SRC activation caused by BMPR2 mutation. SB204741 prevented the development of PAH in BMPR2 mutant mice, reduced recruitment of inflammatory cells to their lungs, and reduced muscularization of their blood vessels. By atomic force microscopy, we determined that BMPR2 mutant mice normally had a doubling of vessel stiffness, which was substantially normalized by HTR2B inhibition. SB204741 reduced SRC phosphorylation and downstream activity in BMPR2 mutant mice. Gene expression arrays indicate that the primary changes were in cytoskeletal and muscle contractility genes. These results were confirmed by gel contraction assays showing that HTR2B inhibition nearly normalizes the 400% increase in gel contraction normally seen in BMPR2 mutant smooth muscle cells. Heritable PAH results from increased SRC activation, cellular contraction, and vascular resistance, but antagonism of HTR2B prevents SRC phosphorylation, downstream activity, and PAH in BMPR2 mutant mice. PMID:26863209

  6. Structural Basis for Host Membrane Remodeling Induced by Protein 2B of Hepatitis A Virus

    PubMed Central

    Vives-Adrián, Laia; Garriga, Damià; Buxaderas, Mònica; Fraga, Joana; Pereira, Pedro José Barbosa

    2015-01-01

    ABSTRACT The complexity of viral RNA synthesis and the numerous participating factors require a mechanism to topologically coordinate and concentrate these multiple viral and cellular components, ensuring a concerted function. Similarly to all other positive-strand RNA viruses, picornaviruses induce rearrangements of host intracellular membranes to create structures that act as functional scaffolds for genome replication. The membrane-targeting proteins 2B and 2C, their precursor 2BC, and protein 3A appear to be primarily involved in membrane remodeling. Little is known about the structure of these proteins and the mechanisms by which they induce massive membrane remodeling. Here we report the crystal structure of the soluble region of hepatitis A virus (HAV) protein 2B, consisting of two domains: a C-terminal helical bundle preceded by an N-terminally curved five-stranded antiparallel β-sheet that displays striking structural similarity to the β-barrel domain of enteroviral 2A proteins. Moreover, the helicoidal arrangement of the protein molecules in the crystal provides a model for 2B-induced host membrane remodeling during HAV infection. IMPORTANCE No structural information is currently available for the 2B protein of any picornavirus despite it being involved in a critical process in viral factory formation: the rearrangement of host intracellular membranes. Here we present the structure of the soluble domain of the 2B protein of hepatitis A virus (HAV). Its arrangement, both in crystals and in solution under physiological conditions, can help to understand its function and sheds some light on the membrane rearrangement process, a putative target of future antiviral drugs. Moreover, this first structure of a picornaviral 2B protein also unveils a closer evolutionary relationship between the hepatovirus and enterovirus genera within the Picornaviridae family. PMID:25589659

  7. Lithium insertion in nanostructured TiO(2)(B) architectures.

    PubMed

    Dylla, Anthony G; Henkelman, Graeme; Stevenson, Keith J

    2013-05-21

    Electric vehicles and grid storage devices have potentialto become feasible alternatives to current technology, but only if scientists can develop energy storage materials that offer high capacity and high rate capabilities. Chemists have studied anatase, rutile, brookite and TiO2(B) (bronze) in both bulk and nanostructured forms as potential Li-ion battery anodes. In most cases, the specific capacity and rate of lithiation and delithiation increases as the materials are nanostructured. Scientists have explained these enhancements in terms of higher surface areas, shorter Li(+) diffusion paths and different surface energies for nanostructured materials allowing for more facile lithiation and delithiation. Of the most studied polymorphs, nanostructured TiO2(B) has the highest capacity with promising high rate capabilities. TiO2(B) is able to accommodate 1 Li(+) per Ti, giving a capacity of 335 mAh/g for nanotubular and nanoparticulate TiO2(B). The TiO2(B) polymorph, discovered in 1980 by Marchand and co-workers, has been the focus of many recent studies regarding high power and high capacity anode materials with potential applications for electric vehicles and grid storage. This is due to the material's stability over multiple cycles, safer lithiation potential relative to graphite, reasonable capacity, high rate capability, nontoxicity, and low cost (Bruce, P. G.; Scrosati, B.; Tarascon, J.-M. Nanomaterials for Rechargeable Lithium Batteries. Angew. Chem., Int. Ed.2008, 47, 2930-2946). One of the most interesting properties of TiO2(B) is that both bulk and nanostructured forms lithiate and delithiate through a surface redox or pseudocapacitive charging mechanism, giving rise to stable high rate charge/discharge capabilities in the case of nanostructured TiO2(B). When other polymorphs of TiO2 are nanostructured, they still mainly intercalate lithium through a bulk diffusion-controlled mechanism. TiO2(B) has a unique open crystal structure and low energy Li

  8. Rap2B GTPase: structure, functions, and regulation.

    PubMed

    Zhu, Zhesi; Di, Jiehui; Lu, Zheng; Gao, Keyu; Zheng, Junnian

    2016-06-01

    Rap2B GTPase, a member of Ras-related protein superfamily, was first discovered from a platelet cDNA library in the early 1990s. Since then, it has been reported to play an important role in regulating cellular processes including cytoskeletal organization, cell growth, and proliferation. It can be stimulated and suppressed by a wide range of external and internal inducers, circulating between GTP-bound active state and GDP-bound inactive state. Increasing focus on Ras signaling pathway reveals critical effects of Rap2B on tumorigenesis. In particular, Rap2B behaves in a p53-dependent manner in regulation of apoptosis and migration. Apart from being an oncogenic activator, Rap2B has been found to participate in many other physiological events via diverse downstream effectors. In this review, we present recent studies on the structure, regulation, and multiple biological functions of Rap2B, shedding light on its potential status in treatment of cancer as well as other diseases. PMID:27012552

  9. A study on D0 Run2b stave structural performance

    SciTech Connect

    Lanfranco, Giobatta; /Fermilab

    2002-04-01

    Two different structural solutions have been proposed and studied for the D0 Run2b stave (Figure 1 and Figure 3). The way the stave structural stiffness is achieved in both designs is essentially the same: the structural material is displaced as far as possible from the neutral axis in order to increase the bending moment of the stave. The agreement of the measured data with what has been theoretically predicted is excellent. The C channel stave with dog-bones glued on top of the sensor (stave No.2) has outperformed the other mockups with a predicted sag of 51 {micro}m for a distributed load of 2.28 N/m [0.013 lbf/in] and a consequent natural frequency of 89.2Hz. The other three C channel staves with the dog-bones not glued on the sensor have a bending stiffness that is -19.0%, -10.8%, +4.0% of that of stave No.2, being 11.0%, 7.8%, 15.1% lighter respectively. An optimized stave structural proposal with 130.5% of the design stiffness within the mass budget is presented at the end of this paper.

  10. Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta.

    PubMed

    Kuma, Yvonne; Campbell, David G; Cuenda, Ana

    2004-04-01

    The endogenous glycogen synthase in extracts from mouse skeletal muscle, liver and brain bound specifically to SAPK2b (stress-activated protein kinase 2b)/p38b, but not to other members of the group of SAPK/p38 kinases. Glycogen synthase was phosphorylated in vitro more efficiently by SAPK2b/p38b than by SAPK2a/p38a, SAPK3/p38g or SAPK4/p38d. SAPK2b/p38b phosphorylated glycogen synthase in vitro at residues Ser644, Ser652, Thr718 and Ser724, two of which (Ser644 and Ser652) are also phosphorylated by glycogen synthase kinase 3. Thr718 and Ser724 are novel sites not known to be phosphorylated by other protein kinases. Glycogen synthase becomes phosphorylated at Ser644 in response to osmotic shock; this phosphorylation is prevented by pretreatment of the cells with SB 203580, which inhibits SAPK2a/p38a and SAPK2b/p38b activity. In vitro, phosphorylation of glycogen synthase by SAPK2b/p38b alone had no significant effect on its activity, indicating that phosphorylation at residue Ser644 itself is insufficient to decrease glycogen synthase activity. However, after phosphorylation by SAPK2b/p38b, subsequent phosphorylation at Ser640 by glycogen synthase kinase 3 decreased the activity of glycogen synthase. This decrease was not observed when SAPK2b/p38b activity was blocked with SB 203580. These results suggest that SAPK2b/p38b may be a priming kinase that allows glycogen synthase kinase 3 to phosphorylate Ser640 and thereby inhibit glycogen synthase activity. PMID:14680475

  11. Software systems for modeling articulated figures

    NASA Technical Reports Server (NTRS)

    Phillips, Cary B.

    1989-01-01

    Research in computer animation and simulation of human task performance requires sophisticated geometric modeling and user interface tools. The software for a research environment should present the programmer with a powerful but flexible substrate of facilities for displaying and manipulating geometric objects, yet insure that future tools have a consistent and friendly user interface. Jack is a system which provides a flexible and extensible programmer and user interface for displaying and manipulating complex geometric figures, particularly human figures in a 3D working environment. It is a basic software framework for high-performance Silicon Graphics IRIS workstations for modeling and manipulating geometric objects in a general but powerful way. It provides a consistent and user-friendly interface across various applications in computer animation and simulation of human task performance. Currently, Jack provides input and control for applications including lighting specification and image rendering, anthropometric modeling, figure positioning, inverse kinematics, dynamic simulation, and keyframe animation.

  12. Figure control concepts for segmented reflector telescopes

    NASA Technical Reports Server (NTRS)

    Boussalis, D.; Chu, C. C.; Ih, C.-H. C.; Wang, S. J.; Ryaciotaki-Boussalis, H. A.

    1989-01-01

    Control analysis activities related to the development of figure control technologies for large space telescopes with precision segmented actively controlled primary reflectors are reviewed. The Precision Segmented Reflector (PSR) configuration is described along with the development and use of the PSR models. Geometric and dynamic models, characterization of figure estimation errors and optimal sensor placement, and the development of quasi-static and dynamic control concepts are outlined. The structure of a quasi-static controller is presented, that utilizes edge sensor measurements to estimate displacement errors at the actuator level and generates figure correction commands. The second approach considers decentralization of the reflector system at the panel level, while the third considers decentralization at the actuator level.

  13. [Figures of anima in the Odyssey].

    PubMed

    Meneghello, Mauro

    2012-01-01

    Feminine characters in the Odyssey show different aspects of the archetype: Mother and Anima (C.G. Jung). From an Analytical Psychology perspective the encounters of Odysseus with goddesses: Circe, Calypso, Ino are looked at as different and successive stages of the hero's way into the inconscious, who shows himself in feminine figures, being masculine the consciousness of the hero. Nausicaa is a new, nearly-human figure of Anima who appears after the symbolic death of Odysseus and leads him to the royal couple Alcinous-Arete: in front of them all he finds his new, reborn, personality by creating and narrating his own myth. PMID:25807734

  14. Substrate Recognition of Histone H2B by DUBm

    NASA Astrophysics Data System (ADS)

    Henderson, Elizabeth; Berndsen, Christopher; Wolberger, Cynthia

    2011-03-01

    The SAGA complex is a transcriptional coactivator that regulates gene expression in eukaryotes via histone acetylation and deubiquitination, which are crucial for transcription. Our lab is investigating the SAGA-dependent deubiquitination of histone H2B. The deubiquitinating module (DUBm) of SAGA is comprised of a ubiquitin-specific protease, Ubp8, and three other proteins. It is known that Ubp8 cleaves ubiquitin from histone H2B, however, the specific way in which the enzyme binds to the substrate remains elusive. In order to unravel this mechanism, we attempted to determine the crystal structure of the substrate binding complex. We obtained this substrate by exploiting the techniques of intein chemistry to artificially ubiquitinate a histone H2B peptide, which we then co-crystallized with DUBm. Additionally, we synthesized Ub-K63R-linked chains and Ub-K48-linked chains and co-crystallized them with DUBm.

  15. Expanding Interprofessional EHR Data in i2b2.

    PubMed

    Westra, Bonnie L; Christie, Beverly; Johnson, Steven G; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G; Byrne, Matthew D; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  16. Expanding Interprofessional EHR Data in i2b2

    PubMed Central

    Westra, Bonnie L.; Christie, Beverly; Johnson, Steven G.; Pruinelli, Lisiane; LaFlamme, Anne; Park, Jung In; Sherman, Suzan G.; Byrne, Matthew D.; Ranallo, Piper; Speedie, Stuart

    2016-01-01

    Emerging issues of team-based care, precision medicine, and big data science underscore the need for health information technology (HIT) tools for integrating complex data in consistent ways to achieve the triple aims of improving patient outcomes, patient experience, and cost reductions. The purpose of this study was to demonstrate the feasibility of creating a hierarchical flowsheet ontology in i2b2 using data-derived information models and determine the underlying informatics and technical issues. This study is the first of its kind to use information models that aggregate team-based care across time, disciplines, and settings into 14 information models that were integrated into i2b2 in a hierarchical model. In the process of successfully creating a hierarchical ontology for flowsheet data in i2b2, we uncovered a variety of informatics and technical issues described in this paper. PMID:27570680

  17. caB2B hosting update —

    Cancer.gov

    cancer Bench-to-Beside - caB2B - is an open-source query tool that permits translational research scientists to search and combine data from virtually any caGrid data service. The caB2B suite is composed of three core components: the Web application, the Client Application and the Administrative Module. The caB2B Web Application provides query templates that allow easy search and retrieval of microarray data (from caArray), imaging data (from the National Biomedical Imaging Archive (NBIA)), specimen data (from caTissue) and nanoparticle data (from caNanoLab) across the grid. Searches can be performed on selected locations using either form-based or keyword searches and data can be exported in the CSV format.

  18. Multiple endocrine neoplasia type 2b associated with lichen nitidus.

    PubMed

    Altaykan, Asli; Ersoy-Evans, Sibel; Emre, Serap; Orhan, Diclehan; Güçer, Safak; Erkin, Gül

    2007-01-01

    Multiple endocrine neoplasia (MEN) type 2B syndrome is an autosomal dominantly inherited endocrine disorder with rare skin manifestations. We report the case of a 19-year-old Turkish girl who presented with skin-colored flat papules scattered all over the trunk and extremities. Additionally, she had marfanoid habitus, thick lips, and multiple flesh-colored papules over the inner eyelids and oral mucosa. Histopathological examination of one of the trunk lesions was consistent with lichen nitidus. Her past medical history was significant for medullary thyroid carcinoma. Genetic testing showed a point mutation in exon 16 at codon 918 (M918T) in the RET proto-oncogene. Based on all these findings, MEN type 2B was diagnosed. To the best of our knowledge we report the first case of MEN type 2B associated with lichen nitidus. PMID:17540634

  19. ORM-Based Semantics of B2B Transactions

    NASA Astrophysics Data System (ADS)

    Balsters, H.; van Blommestein, F.

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely neglected by present implementations of standard EDI- or XML-messaging and by B2B webservice implementations. In this paper a precise model is given of the negotiation process. The requirements of a potential Buyer and the offer of a potential Seller are matched and, if the negotiation is successful, a contract is concluded. The negotiation process model is represented in ORM, extended with dynamic constraints. Our model may be implemented in the databases of the trading partners and in message- or service definitions.

  20. Flow Simulation of N2B Hybrid Wing Body Configuration

    NASA Technical Reports Server (NTRS)

    Kim, Hyoungjin; Liou, Meng-Sing

    2012-01-01

    The N2B hybrid wing body aircraft was conceptually designed to meet environmental and performance goals for the N+2 generation transport set by the subsonic fixed wing project. In this study, flow fields around the N2B configuration is simulated using a Reynolds-averaged Navier-Stokes flow solver using unstructured meshes. Boundary conditions at engine fan face and nozzle exhaust planes are provided by response surfaces of the NPSS thermodynamic engine cycle model. The present flow simulations reveal challenging design issues arising from boundary layer ingestion offset inlet and nacelle-airframe interference. The N2B configuration can be a good test bed for application of multidisciplinary design optimization technology.

  1. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  2. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  3. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  4. Histone H2B mutations in inner region affect ubiquitination, centromere function, silencing and chromosome segregation.

    PubMed

    Maruyama, Takeshi; Nakamura, Takahiro; Hayashi, Takeshi; Yanagida, Mitsuhiro

    2006-06-01

    The reiterated nature of histone genes has hampered genetic approach to dissect the role of histones in chromatin dynamics. We here report isolation of three temperature-sensitive (ts) Schizosaccharomyces pombe strains, containing amino-acid substitutions in the sole histone H2B gene (htb1+). The mutation sites reside in the highly conserved, non-helical residues of H2B, which are implicated in DNA-protein or protein-protein interactions in the nucleosome. In the allele of htb1-72, the substitution (G52D) occurs at the DNA binding loop L1, causing disruption of the gene silencing in heterochromatic regions and lagging chromosomes in anaphase. In another allele htb1-223 (P102L) locating in the junction between alpha3 and alphaC, the mutant residue is in contact with H2A and other histones, leading to structural aberrations in the central centromere chromatin and unequal chromosome segregation in anaphase. The third allele htb1-442 (E34K) near alpha1 displayed little defect. Evidence is provided that monoubiquitinated H2B is greatly unstable in P102L mutant, possibly owing to proteasome-independent destruction or enhanced deubiquitination. Histone H2B thus plays an important role in centromere/kinetochore formation. PMID:16688222

  5. Molecular characterization of the spliceosomal proteins U1A and U2B" from higher plants.

    PubMed Central

    Simpson, G G; Clark, G P; Rothnie, H M; Boelens, W; van Venrooij, W; Brown, J W

    1995-01-01

    In addition to their role in pre-mRNA splicing, the human spliceosomal proteins U1A and U2B" are important models of how RNP motif-containing proteins execute sequence-specific RNA binding. Genes encoding U1A and U2B" have been isolated from potato and thereby provide the only evolutionary comparison available for both proteins and represent the only full-length genes encoding plant spliceosomal proteins to have been cloned and characterized. In vitro RNA binding experiments revealed the ability of potato U2B" to interact with human U2A' to enhance sequence-specific binding and to distinguish cognate RNAs of either plant or animal origin. A comparison of the sequence of U1A and U2B" proteins indicated that multiple residues which could affect RNP motif conformation probably govern the specific distinction in RNA binding by these proteins. Since human U1A modulates polyadenylation in vertebrates, the possibility that plant U1A might be exploited in the characterization of this process in plants was examined. However, unlike vertebrate U1A, neither U1A from potato nor Arabidopsis bound their own mRNA and no evidence for binding to upstream efficiency elements in polyadenylation signals was obtained, suggesting that plant U1A is not involved in polyadenylation. Images PMID:7556097

  6. NREL Advanced Research Turbine (ART) Aerodynamic Design of ART-2B Rotor Blades

    SciTech Connect

    Griffin, D.A.

    2000-09-05

    The National Renewable Energy Laboratory (NREL) installed two Advanced Research Turbines (ART) at the National Wind Technology Center near Boulder, Colorado, to use as full-scale test beds for ongoing research efforts, including three-dimensional blade aerodynamics and the effects of various control methods on turbine loads and performance. The Westinghouse WWG-0600 was selected as a baseline configuration for the ART turbines. The first turbine, ART-1, is currently operational and has been used to collect a baseline set of performance and loads data. A second turbine, ART-2A, incorporates several major modifications and may be upgraded further to a configuration designated aRT-2B. Possible features of the ART-2B turbine include a multi-degree of freedom hum and newly designed rotor blades. Global energy concepts, L.L.C. provided engineering support to NREL in designing the components for the ART-2B turbine. This document provides a summary of work performed by GEC on the aerodynamic design of ART-2B rotor blades.

  7. Antigenicity of the Leishmania infantum histones H2B and H4 during canine viscerocutaneous leishmaniasis

    PubMed Central

    Soto, M; Requena, J M; Quijada, L; Perez, M J; Nieto, C G; Guzman, F; Patarroyo, M E; Alonso, C

    1999-01-01

    In this study we show that sera from dogs naturally infected with Leishmania infantum contain antibodies that specifically react against the parasite H2B and H4 histones. The Leishmania H2B and the amino-terminal region of the histone H4, expressed as fusion proteins, when confronted with sera from canine viscerocutaneous leishmaniasis (VCL) dogs, were recognized by 63% and 47%, respectively. No reactivity was detected when sera from dogs naturally infected with pathogens other than Leishmania were used. Using a collection of synthetic peptides covering the complete sequence of both proteins, we have determined that the main linear antigenic determinants are located in the amino-terminal domains of these histones. The humoral response against histones H2B and H4 induced during canine leishmaniasis was found to be specific for Leishmania histones, since no cross-reactivity of the VCL sera with mammal histones was observed. Also, a comparative study of the prevalence of antibodies among VCL sera against the four core histones of L. infantum was performed. Although a large heterogeneity of the humoral responses against these proteins was found, histones H2A and H3 seem to be more prevalent immunogens than histones H2B and H4 during canine natural leishmaniasis. The origin of the anti-histone humoral response and its possible implications in the pathogenesis of Leishmania infection are discussed. PMID:9933463

  8. Thioredoxin-like protein 2b facilitates colon cancer cell proliferation and inhibits apoptosis via NF-κB pathway.

    PubMed

    Lu, Yuanyuan; Zhao, Xiaodi; Luo, Guanhong; Shen, Gaofei; Li, Kai; Ren, Gui; Pan, Yan; Wang, Xin; Fan, Daiming

    2015-07-28

    Our previous work identified thioredoxin-like protein 2 (Txl-2), a novel thioredoxin family member, as the target of the monoclonal antibody MC3 which can detect colon cancer with high sensitivity and specificity. In the present study, the function of the most abundant isoform Txl-2b in cell proliferation and apoptosis was investigated. Txl-2 overexpression correlated with increased clinical stages. Inhibition of Txl-2b suppressed cell proliferation, induced cell cycle arrest at the G1/S phase, and led to responsiveness to the vincristine-induced apoptosis in SW620 cells. Txl-2b overexpression in LoVo cells had the opposite effect, which was dependent on Trx domain function. In vivo studies validated that Txl-2b expression promoted colon cancer tumorigenesis in nude mice. Further studies revealed that nuclear factor-κB (NF-κB) signaling was activated by Txl-2b. Inhibition of NF-κB activation partly abrogated the pro-proliferation and anti-apoptotic phenotypes mediated by Txl-2b via reduced Cyclin D1, Bcl-2, Bcl-xL and Survivin expression and increased Caspase-3 activation. Overall, our results indicate that Txl-2b expression stimulates cancer cell proliferation, accelerates the cell cycle and contributes to apoptosis resistance in colon cancer and provides a potential therapeutic target for colon cancer treatment. PMID:25555669

  9. Upregulation of UGT2B4 Expression by 3'-Phosphoadenosine-5'-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation.

    PubMed

    Barrett, Kathleen G; Fang, Hailin; Cukovic, Daniela; Dombkowski, Alan A; Kocarek, Thomas A; Runge-Morris, Melissa

    2015-07-01

    During cholestasis, the bile acid-conjugating enzymes, SULT2A1 and UGT2B4, work in concert to prevent the accumulation of toxic bile acids. To understand the impact of sulfotransferase deficiency on human hepatic gene expression, we knocked down 3'-phosphoadenosine-5'-phosphosulfate synthases (PAPSS) 1 and 2, which catalyze synthesis of the obligate sulfotransferase cofactor, in HepG2 cells. PAPSS knockdown caused no change in SULT2A1 expression; however, UGT2B4 expression increased markedly (∼41-fold increase in UGT2B4 mRNA content). Knockdown of SULT2A1 in HepG2 cells also increased UGT2B4 expression. To investigate the underlying mechanism, we transfected PAPSS-deficient HepG2 cells with a luciferase reporter plasmid containing ∼2 Kb of the UGT2B4 5'-flanking region, which included a response element for the bile acid-sensing nuclear receptor, farnesoid X receptor (FXR). FXR activation or overexpression increased UGT2B4 promoter activity; however, knocking down FXR or mutating or deleting the FXR response element did not significantly decrease UGT2B4 promoter activity. Further evaluation of the UGT2B4 5'-flanking region indicated the presence of distal regulatory elements between nucleotides -10090 and -10037 that negatively and positively regulated UGT2B4 transcription. Pulse-chase analysis showed that increased UGT2B4 expression in PAPSS-deficient cells was attributable to both increased mRNA synthesis and stability. Transfection analysis demonstrated that the UGT2B4 3'-untranslated region decreased luciferase reporter expression less in PAPSS-deficient cells than in control cells. These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity, presumably to maintain bile acid-conjugating activity. PMID:25948711

  10. The selectivity of conantokin-G for ion channel inhibition of NR2B subunit-containing NMDA receptors is regulated by amino acid residues in the S2 region of NR2B.

    PubMed

    Sheng, Zhenyu; Liang, Zhong; Geiger, James H; Prorok, Mary; Castellino, Francis J

    2009-08-01

    The conantokins are short, naturally occurring peptides that inhibit ion flow through N-methyl-d-aspartate receptor (NMDAR) channels. One member of this peptide family, conantokin-G (con-G), shows high selectivity for antagonism of NR2B-containing NMDAR channels, whereas other known conantokins are less selective inhibitors with regard to the nature of the NR2 subunit of the NMDAR complex. In order to define the molecular determinants of NR2B that govern con-G selectivity, we evaluated the ability of con-G to inhibit NMDAR ion channels expressed in human embryonic kidney (HEK)293 cells transfected with NR1, in combination with various NR2A/2B chimeras and point mutants, by electrophysiology using cells voltage-clamped in the whole-cell configuration. We found that a variant of the con-G-insensitive subunit, NR2A, in which the 158 residues comprising the S2 peptide segment (E(657)-I(814)) were replaced by the corresponding S2 region of NR2B (E(658)-I(815)), results in receptors that are highly sensitive to inhibition by con-G. Of the 22 amino acids that are different between the NR2A-S2 and the NR2B-S2 regions, exchange of one of these, M(739) of NR2B for the equivalent K(738) of NR2A, was sufficient to completely import the inhibitory activity of con-G into NR1b/NR2A-containing NMDARs. Some reinforcement of this effect was found by substitution of a second amino acid, K(755) of NR2B for Y(754) of NR2A. The discovery of the molecular determinants of NR2B selectivity with con-G has implications for the design of subunit-selective neurobiological probes and drug therapies, in addition to advancing our understanding of NR2B- versus NR2A-mediated neurological processes. PMID:19427876

  11. Adolescent Girls' Parasocial Interactions with Media Figures

    ERIC Educational Resources Information Center

    Theran, Sally A.; Newberg, Emily M.; Gleason, Tracy R.

    2010-01-01

    We examined aspects of adolescent girls' parasocial interactions in the context of typical development. Parasocial interactions are defined as symbolic, one-sided quasi-interactions between a viewer and a media figure. In total, 107 adolescent girls were examined; 94% reported engaging in parasocial interactions to some degree. Preoccupied…

  12. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  13. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  14. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  15. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  16. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  17. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  18. Fading-Figure Tracing in Williams Syndrome

    ERIC Educational Resources Information Center

    Nagai, Chiyoko; Inui, Toshio; Iwata, Makoto

    2011-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe impairment of visuospatial abilities. Figure-drawing abilities, which are thought to reflect visuospatial abilities, have yet to be fully investigated in WS. The purpose of the present study was to clarify whether drawing abilities differ between WS individuals and…

  19. Participation in the Figured World of Graffiti

    ERIC Educational Resources Information Center

    Valle, Imuris; Weiss, Eduardo

    2010-01-01

    This article is based on ethnographic work with two "crews" of young graffiti artists in southern Mexico City. The crews share certain characteristics with gangs or urban tribes, but more with "communities of practice": they live in the "figured world" of graffiti, a community of practice at the local and global level. Through participation,…

  20. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  1. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  2. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  3. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  4. Cylindrical optic figuring dwell time optimization

    NASA Astrophysics Data System (ADS)

    Waluschka, Eugene

    2000-11-01

    The Constellation-X, grazing incidence, x-ray telescope may be fabricated from replicated segments. A series of mandrels will serve as the 'masters' in the replication processes. Diamond turning (milling) followed by abrasive figuring followed by a super polishing are the steps currently envisioned in making just one (of many) mandrel. The abrasive figuring of a mandrel is accomplished by moving a grinding tool along a helical path on this almost cylindrical surface. The measurement of the surface is, however, performed along 'axial' scan lines which intercept this helical path. This approach to figuring and measuring permits a relatively simple scheme to be implemented for the determination of the optimal dwell times of the figuring tool. These optimal dwell times are determined by a deconvolution which approaches the problem in a linear programming context and uses the Simplex Method. The approach maximizes the amount of material removed at any point subject to inequality constraints. The effects of using these 'optimum' dwell times is to significantly improve the tools effectiveness at removing the higher spatial frequencies while staying (strictly) within the bounds and constraints imposed by the hardware. In addition, the ringing at the edges of the optic, frequently present in deconvolution problems, is completely eliminated.

  5. Go Figure. HEADJAM. Teaching Guide [and Videotape].

    ERIC Educational Resources Information Center

    MATHCOUNTS Foundation, Alexandria, VA.

    The HeadJam series is comprised of six programs exploring mathematics, science, and critical thinking skills. It is an award-winning, educational videotape series for middle school students that explores multi-disciplinary skills in a highly entertaining way. The teacher's guide and 22-minute video, "Go Figure," demonstrate how math is used in the…

  6. The Offerings of Fringe Figures and Migrants

    ERIC Educational Resources Information Center

    Engels-Schwarzpaul, A.-Chr.

    2015-01-01

    "The Western tradition", as passe-partout, includes fringe figures, émigrés and migrants. Rather than looking to resources at the core of the Western tradition to overcome its own blindnesses, I am more interested in its gaps and peripheries, where other thoughts and renegade knowledges take hold. It is in the contact zones with…

  7. Mirror Figuring Techniques of Sir William Herschel

    NASA Astrophysics Data System (ADS)

    Albin, E. F.

    2004-05-01

    Between the years 1773 to 1818, Sir William Herschel constructed dozens of speculum telescope mirrors, with diameters ranging from 6 - 48 inches. Very little, if any, detailed information has ever been published on the specifics of his mirror figuring efforts. The reason for this certainly relates to his desire to closely guard mirror production trade secrets. Upon Herschel's death, all telescope-making documents were passed on to his only son, Sir John Herschel. These materials are now in the possession of the British RAS and primarily consist of: a) a four volume series entitled "Experiments on the Construction of Specula," b) a 129 page treaty called "On the Construction of Specula," and c) a 179 page manuscript entitled "Results of Experiments on the Construction of Mirrors." It is suggested that publication was further delayed and then eventually abandoned due to silver-coated glass mirrors coming into favor. A recent investigation by the author, of the unpublished manuscripts on the construction of specula, suggests that Herschel's mirror figuring techniques did not involve any guess work; in fact, his methods were highly refined -- never leaving to chance the evolution of a spherical surface into the required paraboloid. At the heart of Herschel's figuring techniques were a series of aperture diaphragms (similar to the Couder masks used by modern telescope makers) that were placed over the mirror, which allowed for the precise determination of its curvature at various predefined zones. With this information, Herschel was able to vary his figuring strokes with his polishing tool accordingly. In addition, all mirrors were subsequently "star tested," sometimes with aperture diaphragms in place, allowing for field examination of the mirror's "distinctness" or performance. Double stars and the planet Saturn were favorite targets used to analyze and then correct a mirror's figure.

  8. 27 CFR 21.33 - Formula No. 2-B.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Formula No. 2-B. 21.33 Section 21.33 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL FORMULAS FOR DENATURED ALCOHOL AND RUM Specially Denatured Spirits...

  9. Strategies for maintaining patient privacy in i2b2

    PubMed Central

    Gainer, Vivian; Mendis, Michael; Churchill, Susanne; Kohane, Isaac

    2011-01-01

    Background The re-use of patient data from electronic healthcare record systems can provide tremendous benefits for clinical research, but measures to protect patient privacy while utilizing these records have many challenges. Some of these challenges arise from a misperception that the problem should be solved technically when actually the problem needs a holistic solution. Objective The authors' experience with informatics for integrating biology and the bedside (i2b2) use cases indicates that the privacy of the patient should be considered on three fronts: technical de-identification of the data, trust in the researcher and the research, and the security of the underlying technical platforms. Methods The security structure of i2b2 is implemented based on consideration of all three fronts. It has been supported with several use cases across the USA, resulting in five privacy categories of users that serve to protect the data while supporting the use cases. Results The i2b2 architecture is designed to provide consistency and faithfully implement these user privacy categories. These privacy categories help reflect the policy of both the Health Insurance Portability and Accountability Act and the provisions of the National Research Act of 1974, as embodied by current institutional review boards. Conclusion By implementing a holistic approach to patient privacy solutions, i2b2 is able to help close the gap between principle and practice. PMID:21984588

  10. The Sheep Tetherin Paralog oBST2B Blocks Envelope Glycoprotein Incorporation into Nascent Retroviral Virions

    PubMed Central

    Murphy, Lita; Varela, Mariana; Desloire, Sophie; Ftaich, Najate; Murgia, Claudio; Golder, Matthew; Neil, Stuart; Spencer, Thomas E.; Wootton, Sarah K.; Lavillette, Dimitri; Terzian, Christophe; Palmarini, Massimo

    2014-01-01

    ABSTRACT Bone marrow stromal cell antigen 2 (BST2) is a cellular restriction factor with a broad antiviral activity. In sheep, the BST2 gene is duplicated into two paralogs termed oBST2A and oBST2B. oBST2A impedes viral exit of the Jaagsiekte sheep retroviruses (JSRV), most probably by retaining virions at the cell membrane, similar to the “tethering” mechanism exerted by human BST2. In this study, we provide evidence that unlike oBST2A, oBST2B is limited to the Golgi apparatus and disrupts JSRV envelope (Env) trafficking by sequestering it. In turn, oBST2B leads to a reduction in Env incorporation into viral particles, which ultimately results in the release of virions that are less infectious. Furthermore, the activity of oBST2B does not seem to be restricted to retroviruses, as it also acts on vesicular stomatitis virus glycoproteins. Therefore, we suggest that oBST2B exerts antiviral activity using a mechanism distinct from the classical tethering restriction observed for oBST2A. IMPORTANCE BST2 is a powerful cellular restriction factor against a wide range of enveloped viruses. Sheep possess two paralogs of the BST2 gene called oBST2A and oBST2B. JSRV, the causative agent of a transmissible lung cancer of sheep, is known to be restricted by oBST2A. In this study, we show that unlike oBST2A, oBST2B impairs the normal cellular trafficking of JSRV envelope glycoproteins by sequestering them within the Golgi apparatus. We also show that oBST2B decreases the incorporation of envelope glycoprotein into JSRV viral particles, which in turn reduces virion infectivity. In conclusion, oBST2B exerts a novel antiviral activity that is distinct from those of BST2 proteins of other species. PMID:25339764

  11. Progress in the discovery of selective, high affinity A(2B) adenosine receptor antagonists as clinical candidates.

    PubMed

    Kalla, Rao V; Zablocki, Jeff

    2009-03-01

    The selective, high affinity A(2B) adenosine receptor (AdoR) antagonists that were synthesized by several research groups should aid in determining the role of the A(2B) AdoR in inflammatory diseases like asthma or rheumatoid arthritis (RA) and angiogenic diseases like diabetic retinopathy or cancer. CV Therapeutics scientists discovered the selective, high affinity A(2B) AdoR antagonist 10, a 8-(4-pyrazolyl)-xanthine derivative [CVT-6883, K(i)(hA(2B)) = 22 nM; K(i)(hA(1)) = 1,940 nM; K(i)(hA(2A)) = 3,280; and K(i)(hA(3)) = 1,070 nM] that has favorable pharmacokinetic (PK) properties (t (1/2) = 4 h and F > 35% rat). Compound 10 demonstrated functional antagonism at the A(2B) AdoR (K(B) = 6 nM) and efficacy in a mouse model of asthma. In two phase 1 clinical trials, CVT-6883 was found to be safe, well tolerated, and suitable for once daily dosing. A second compound 20, 8-(5-pyrazolyl)-xanthine, has been nominated for development from Baraldi's group in conjunction with King Pharmaceuticals that has favorable A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 5.5 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 1,000; and K(i)(hA(3)) > 1,000 nM], and it has been demonstrated to be a functional antagonist. A third compound 32, a 2-aminopyrimidine, from the Almirall group has high A(2B) AdoR affinity and selectivity [K(i)(hA(2B)) = 17 nM; K(i)(hA(1)) > 1,000 nM; K(i)(hA(2A)) > 2,500; and K(i)(hA(3)) > 1,000 nM], and 32 has been moved into preclinical safety testing. Since three highly selective, high affinity A(2B) AdoR antagonists have been nominated for development with 10 (CVT-6883) being the furthest along in the development process, the role of the A(2B) AdoR in various disease states will soon be established. PMID:18568423

  12. The 2B domain of the Escherichia coli Rep protein is not required for DNA helicase activity.

    PubMed

    Cheng, Wei; Brendza, Katherine M; Gauss, George H; Korolev, Sergey; Waksman, Gabriel; Lohman, Timothy M

    2002-12-10

    The Escherichia coli Rep protein is a 3' to 5' SF1 DNA helicase required for replication of bacteriophage phiX174 in E. coli, and is structurally homologous to the E. coli UvrD helicase and the Bacillus stearothermophilus PcrA helicase. Previous crystallographic studies of Rep protein bound to single-stranded DNA revealed that it can undergo a large conformational change consisting of an approximately 130 degrees rotation of its 2B subdomain about a hinge region connected to the 2A subdomain. Based on crystallographic studies of PcrA, its 2B subdomain has been proposed to form part of its duplex DNA binding site and to play a role in duplex destabilization. To test the role of the 2B subdomain in Rep-catalyzed duplex DNA unwinding, we have deleted its 2B subdomain, replacing it with three glycines, to form the RepDelta2B protein. This RepDelta2B protein can support phiX174 replication in a rep(-) E. coli strain, although the growth rate of E. coli containing the repDelta2B gene is approximately 1.5-fold slower than with the wild-type rep gene. Pre-steady-state, single-turnover DNA unwinding kinetics experiments show that purified RepDelta2B protein has DNA helicase activity in vitro and unwinds an 18-bp DNA duplex with rates at least as fast as wild-type Rep, and with higher extents of unwinding and higher affinity for the DNA substrate. These studies show that the 2B domain of Rep is not required for DNA helicase activity in vivo or in vitro, and that it does not facilitate DNA unwinding in vitro. PMID:12441398

  13. Distribution of galanin receptor 2b neurons and interaction with galanin in the zebrafish central nervous system.

    PubMed

    Kim, Eunmi; Jeong, Inyoung; Kim, Suhyun; Kim, Hwan-Ki; Lee, Dong-Won; Kim, Boa; Seong, Jae Young; Bae, Young-Ki; Ryu, Jae-Ho; Park, Hae-Chul

    2016-08-15

    Galanin is a multifunctional neuropeptide that is implicated in the modulation of physiological processes, including nociception, cognition, feeding behavior, neuronal growth, and reproduction. The physiological effects of galanin are mediated through its interaction with three different G protein-coupled receptors, i.e., GALR1, GALR2, and GALR3. Unlike mammals, zebrafish have four different receptors for galanin, diversified from GALR1 (GAL1a and GALR1b) and GALR2 (GALR2a and GALR2b). Despite the importance of galanin in the central nervous system (CNS), no information has been reported regarding GalR2 in zebrafish CNS. In this study, we found that galr2a is expressed at low levels in restricted areas of the brain; however, galr2b was widely expressed in CNS including olfactory bulb, midbrain tegmentum, preoptic region, dorsal thalamus, posterior tuberculum, postoptic commissure, hindbrain, and spinal cord. To further analyze the distribution of GALR2b neurons and their interaction with GAL, we generated Tg(galr2b:egfp) zebrafish, which express enhanced green fluorescent protein (EGFP) under the control of a galr2b promoter. Investigation of the CNS of transgenic reporter zebrafish revealed that galr2b:EGFP(+) neurons are distributed and interact with galanin-immunoreactive (galanin-IR) cells in various regions of the brain and spinal cord. We found that in some regions of the brain and spinal cord, galanin-IR nerve cells were not observed near galr2b:EGFP neurons, suggesting that GALR2b may have the potential to interact with other ligands instead of galanin in these regions. PMID:27315774

  14. Mutations of the human interferon alpha-2b (hIFNα-2b) gene in cancer patients receiving radiotherapy

    PubMed Central

    Shahid, Saman; Chaudhry, Muhammad Nawaz; Mahmood, Nasir

    2015-01-01

    This research aimed to find out the impact of ionizing radiations on the hIFNα-2b gene of radiotherapy treated cancer patients. The gene hIFNα-2b synthesizes a protein which is an important anticancerous and antiviral protein. The cancer patients (breast, lung, thyroid, oral and prostate) who were undergoing a radiotherapy treatment were selected. A molecular analysis was performed for DNA isolation and gene amplification through PCR, to identify gene mutations. Further, by bioinformatics tools we concluded that how mutations identified in gene sequences have led to the alterations in the hINFα-2b protein in radiotherapy receiving cancer patients. The 32% mutations in the hINFα-2b gene were identified and all were frameshift mutations. Radiotherapy can impact the immune system and cancer patients may modulate their immunity. Understaning the mechanisms of radiotherapy-elicited immune response may be helpful in the development of those therapeutic interventions that can enhance the efficacy of radiotherapy. PMID:26396921

  15. D1((2)B2g) to D0((2)Au) Fluorescence from the Matrix-Isolated Perylene Cation Following Laser Excitation into the D5(2)B3g) and D2 ((2)B3g) Electronic States

    NASA Technical Reports Server (NTRS)

    Chillier, Xavier D. F.; Stone, Bradley M.; Joblin, Christine; Salama, Farid; Allamandola, Louis J.; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    Fluorescence spectra of the perylene cation, pumped by direct laser excitation via the D(sub 2)((2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) and D(sub 5)(2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) transitions, are presented. Direct excitation into the D5 or D2 states is followed by rapid non-radiative relaxation to D1 that, in turn,relaxes radiatively. Excitation spectroscopy across the D(sub 2)((2)B(sub 3g)) (left arrow) D(sub 0)((2)A(sub u)) transition near 730 nm shows that site splitting plays little or no role in determining the spectral substructure in the ion spectra. Tentative assignments for ground state vibrational frequencies are made by comparison of spectral intervals with calculated normal mode frequencies.

  16. Evolution of seismic layer 2B across the Juan de Fuca Ridge from hydrophone streamer 2-D traveltime tomography

    NASA Astrophysics Data System (ADS)

    Newman, Kori R.; Nedimović, Mladen R.; Canales, J. Pablo; Carbotte, Suzanne M.

    2011-05-01

    How oceanic crust evolves has important implications for understanding both subduction earthquake hazards and energy and mass exchange between the Earth's interior and the oceans. Although considerable work has been done characterizing the evolution of seismic layer 2A, there has been little analysis of the processes that affect layer 2B after formation. Here we present high-resolution 2-D tomographic models of seismic layer 2B along ˜300 km long multichannel seismic transects crossing the Endeavour, Northern Symmetric, and Cleft segments of the Juan de Fuca Ridge. These models show that seismic layer 2B evolves rapidly following a different course than layer 2A. The upper layer 2B velocities increase on average by 0.8 km/s and reach a generally constant velocity of 5.2 ± 0.3 km/s within the first 0.5 Myr after crustal formation. This suggests that the strongest impact on layer 2B evolution may be that of mineral precipitation due to "active" hydrothermal circulation centered about the ridge crest and driven by the heat from the axial magma chamber. Variations in upper layer 2B velocity with age at time scales ≥0.5 Ma show correlation about the ridge axis indicating that in the long term, crustal accretion processes affect both sides of the ridge axis in a similar way. Below the 0.5 Ma threshold, differences in 2B velocity are likely imprinted during crustal formation or early crustal evolution. Layer 2B velocities at propagator wakes (5.0 ± 0.2 km/s), where enhanced faulting and cracking are expected, and at areas that coincide with extensional or transtensional faulting are on average slightly slower than in normal mature upper layer 2B. Analysis of the layer 2B velocities from areas where the hydrothermal patterns are known shows that the locations of current and paleohydrothermal discharge and recharge zones are marked by reduced and increased upper layer 2B velocities, respectively. Additionally, the distance between present up-flow and down-flow zones is

  17. Variable-spot ion beam figuring

    NASA Astrophysics Data System (ADS)

    Wu, Lixiang; Qiu, Keqiang; Fu, Shaojun

    2016-03-01

    This paper introduces a new scheme of ion beam figuring (IBF), or rather variable-spot IBF, which is conducted at a constant scanning velocity with variable-spot ion beam collimated by a variable diaphragm. It aims at improving the reachability and adaptation of the figuring process within the limits of machine dynamics by varying the ion beam spot size instead of the scanning velocity. In contrast to the dwell time algorithm in the conventional IBF, the variable-spot IBF adopts a new algorithm, which consists of the scan path programming and the trajectory optimization using pattern search. In this algorithm, instead of the dwell time, a new concept, integral etching time, is proposed to interpret the process of variable-spot IBF. We conducted simulations to verify its feasibility and practicality. The simulation results indicate the variable-spot IBF is a promising alternative to the conventional approach.

  18. Figure correction of multilayer coated optics

    DOEpatents

    Chapman; Henry N. , Taylor; John S.

    2010-02-16

    A process is provided for producing near-perfect optical surfaces, for EUV and soft-x-ray optics. The method involves polishing or otherwise figuring the multilayer coating that has been deposited on an optical substrate, in order to correct for errors in the figure of the substrate and coating. A method such as ion-beam milling is used to remove material from the multilayer coating by an amount that varies in a specified way across the substrate. The phase of the EUV light that is reflected from the multilayer will be affected by the amount of multilayer material removed, but this effect will be reduced by a factor of 1-n as compared with height variations of the substrate, where n is the average refractive index of the multilayer.

  19. Recommended Figures of Merit for Green Monopropellants

    NASA Technical Reports Server (NTRS)

    Marshall, William M.; Deans, Matthew C.

    2013-01-01

    Hydrazine propellant has historically been used as a rocket thruster monopropellant since the mid-1960s. Mission managers are well aware of its characteristics and performance. However, it is a known toxic chemical and a wide effort is underway to reduce and/or eliminate its use worldwide. Several new propellant combinations have been developed in the last few years which tout or promise to provide same or better performance as hydrazine while being "non-toxic" or "green". Yet, there is no consistent definition for what constitutes "non-toxic" or "green", and thus no good figure of merit for which to compare. This paper seeks to review the three major categories of figures of merit, and discusses how they might be used to assess the viability of a propellant.

  20. Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import*

    PubMed Central

    Di Lascio, Simona; Belperio, Debora

    2016-01-01

    Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity. PMID:27129232

  1. Alanine Expansions Associated with Congenital Central Hypoventilation Syndrome Impair PHOX2B Homeodomain-mediated Dimerization and Nuclear Import.

    PubMed

    Di Lascio, Simona; Belperio, Debora; Benfante, Roberta; Fornasari, Diego

    2016-06-17

    Heterozygous mutations of the human PHOX2B gene, a key regulator of autonomic nervous system development, lead to congenital central hypoventilation syndrome (CCHS), a neurodevelopmental disorder characterized by a failure in the autonomic control of breathing. Polyalanine expansions in the 20-residues region of the C terminus of PHOX2B are the major mutations responsible for CCHS. Elongation of the alanine stretch in PHOX2B leads to a protein with altered DNA binding, transcriptional activity, and nuclear localization and the possible formation of cytoplasmic aggregates; furthermore, the findings of various studies support the idea that CCHS is not due to a pure loss of function mechanism but also involves a dominant negative effect and/or toxic gain of function for PHOX2B mutations. Because PHOX2B forms homodimers and heterodimers with its paralogue PHOX2A in vitro, we tested the hypothesis that the dominant negative effects of the mutated proteins are due to non-functional interactions with the wild-type protein or PHOX2A using a co-immunoprecipitation assay and the mammalian two-hybrid system. Our findings show that PHOX2B forms homodimers and heterodimerizes weakly with mutated proteins, exclude the direct involvement of the polyalanine tract in dimer formation, and indicate that mutated proteins retain partial ability to form heterodimers with PHOX2A. Moreover, in this study, we investigated the effects of the longest polyalanine expansions on the homeodomain-mediated nuclear import, and our data clearly show that the expanded C terminus interferes with this process. These results provide novel insights into the effects of the alanine tract expansion on PHOX2B folding and activity. PMID:27129232

  2. Structural stability of W2B5 under high pressure

    NASA Astrophysics Data System (ADS)

    Kumar, N. R. Sanjay; Shekar, N. V. Chandra; Sahu, P. Ch.

    2015-05-01

    High-pressure structural stability studies have been carried out on tungsten boride W2B5 up to maximum pressure of 36 GPa using a Mao-Bell diamond-anvil cell at beamline BR-12 of the ELETTRA synchrotron facility (λ = 0.68881 Å). The hexagonal phase (S.G:P63/mmc) of W2B5 is stable up to the maximum pressure studied. The bulk modulus is estimated to be ~347 GPa using the Birch-Murnaghan equation of state. The variation of lattice parameters and bond lengths B-B and W-B have been studied and the c-axis is seen to be marginally more compressible than the a-axis.

  3. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  4. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point * (degrees F) Criteria Reactivityfactor 1 80-205 Alkanes... + Dry Point) / 2 (b) Aromatic Hydrocarbon Solvents...

  5. Flux Line Lattice Structure in YNi2B2C

    NASA Astrophysics Data System (ADS)

    Kawano-Furukawa, Hazuki; Ohira-Kawamura, Seiko; Tsukagoshi, Hitomi; Kobayashi, Chiyako; Nagata, Takashi; Sakiyama, Naoki; Yoshizawa, Hideki; Yethiraj, Mohana; Suzuki, Jun-ichi; Takeya, Hiroyuki

    2008-10-01

    Recently Nakai et al. reported a theoretical H-T phase diagram of flux line lattice (FLL) structure in which successive transitions from a triangular, a square (\\squarev), a triangular and another square (\\squareg) occur with increasing a magnetic field. Here \\squarev and \\squareg indicate the FLL structures reflecting anisotropies in the Fermi velocity and the superconducting gap, respectively. In the case of YNi2B2C, \\squarev and \\squareg should rotate by 45°. The low field transition from triangular to \\squarev is observed in RENi2B2C (\\textit{RE}=Er, Tm, Lu, and Y). However, there is no experimental evidence for the appearance of \\squareg phase so far. We studied the FLL structure of YNi2B2C in the higher field region by small-angle neutron scattering. Our results show that a large area of the H-T phase diagram is occupied by \\squarev phase and there is no evidence for the appearance of \\squareg lattice.

  6. Agent-based services for B2B electronic commerce

    NASA Astrophysics Data System (ADS)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  7. Association of genetic variants of GRIN2B with autism.

    PubMed

    Pan, Yongcheng; Chen, Jingjing; Guo, Hui; Ou, Jianjun; Peng, Yu; Liu, Qiong; Shen, Yidong; Shi, Lijuan; Liu, Yalan; Xiong, Zhimin; Zhu, Tengfei; Luo, Sanchuan; Hu, Zhengmao; Zhao, Jingping; Xia, Kun

    2015-01-01

    Autism (MIM 209850) is a complex neurodevelopmental disorder characterized by social communication impairments and restricted repetitive behaviors. It has a high heritability, although much remains unclear. To evaluate genetic variants of GRIN2B in autism etiology, we performed a system association study of common and rare variants of GRIN2B and autism in cohorts from a Chinese population, involving a total sample of 1,945 subjects. Meta-analysis of a triad family cohort and a case-control cohort identified significant associations of multiple common variants and autism risk (Pmin = 1.73 × 10(-4)). Significantly, the haplotype involved with the top common variants also showed significant association (P = 1.78 × 10(-6)). Sanger sequencing of 275 probands from a triad cohort identified several variants in coding regions, including four common variants and seven rare variants. Two of the common coding variants were located in the autism-related linkage disequilibrium (LD) block, and both were significantly associated with autism (P < 9 × 10(-3)) using an independent control cohort. Burden analysis and case-only analysis of rare coding variants identified by Sanger sequencing did not find this association. Our study for the first time reveals that common variants and related haplotypes of GRIN2B are associated with autism risk. PMID:25656819

  8. Figures of Equilibrium among Binary Asteroids

    NASA Astrophysics Data System (ADS)

    Hestroffer, D.; Tanga, P.

    2005-12-01

    The original idea of Farinella et al. [1] that rubble pile asteroids can have figures of equilibrium, is rehabilitated. Albeit asteroids generally have a broad distribution of shapes and do not follow sequences of (hydrostatic) equilibrium, we show that some asteroids are indeed Jacobi or Darwin ellipsoids. Such statement is obtained from an analysis of their ellipsoidal shape (a:b:c) together with recent measures of their mass and bulk density [2,3]. This means that both their shape and adimensional rotation frequency sbond Ω =Ω /(π ρ G) follow sequences of equilibrium [4,5]. Jacobi and Darwin figures are obtained for uniformly rotating mass of (inviscid as well as compressible) fluids and relatively large angular momentum. Interestingly these objects appear to preferably be binaries. We moreover show that the porosity of such objects is relatively large (approx. 40%) indicating that they are loose rubble piles, yet with dense packing. Last we show that, given the observed bulk-densities, these bodies must be homogeneous bodies of uniform density distribution. Thus, though solid-solid friction must occur in such aggregates, the surface of these bodies is a surface of level similar to that of inviscid fluids. Comparison to other asteroids of similar mass either possessing a moonlet or with no known satellites should shed light on their formation history and/or constrains on collisional evolution. Binaries with low eccentricities and inclination (hence prograde orbit) should preferably be the outcome of catastrophic disruption as is supposed for members of dynamical family [6,7]. Future work and analysis of the typical reaccumulation time scales, typical angular momentum, possible post-reaccumulation cosmic shaking, etc. shall help to know how the fate of collisions or catastrophic breakup of a parent body can differ yielding to binaries with equilibrium figures. In any case the existence of a figure of equilibrium appears to be highly correlated to the presence

  9. Regulation of Human UGT2B15 and UGT2B17 by miR-376c in Prostate Cancer Cell Lines.

    PubMed

    Wijayakumara, Dhilushi D; Hu, Dong Gui; Meech, Robyn; McKinnon, Ross A; Mackenzie, Peter I

    2015-09-01

    Given the prime importance of UDP-glucuronosyltransferase (UGT) 2B15 and UGT2B17 in inactivating testosterone and dihydrotestosterone, control of their expression and activity in the prostate is essential for androgen signaling homeostasis in this organ. Although several studies provide evidence of transcriptional control of UGT2B15 and UGT2B17 by various endogenous and exogenous compounds, potential post-transcriptional regulation of UGT2B15 and UGT2B17 by microRNAs (miRs) in prostate cancer cells has not been examined. The present study identified a putative miR-376c target site in the 3'-untranslated regions (UTRs) of both UGT2B15 and UGT2B17 mRNAs. In accordance with the possibility that this miRNA negatively regulates UGT2B15 and UGT2B17 expression, there is an inverse correlation in the levels of miR-376c and UGT2B15/UGT2B17 mRNAs in prostate cancer cell lines versus normal prostate tissue. In LNCaP cells, transfection of miR-376c mimics inhibited the glucuronidations of testosterone, 4-methylumbelliferone (a substrate of UGT2B15), and androsterone (a substrate of UGT2B17). miR-376c reduced both UGT2B15 and UGT2B17 mRNA and protein levels and the activity of luciferase reporters containing UGT2B15 or UGT2B17 3'-UTRs. This microRNA-mediated repression was significantly abrogated by mutating the miR-376c binding site in the 3'-UTRs of both UGTs. Collectively, these data indicate that the expression of UGT2B15 and UGT2B17 is negatively regulated by the binding of miR-376c to the 3'-UTRs of UGT2B15 and UGT2B17 in prostate cancer cells. This represents the first evidence for post-transcriptional regulation of UGT2B15 and UGT2B17 by miRNAs in prostate cancer cells and may have importance in regulating androgen receptor signaling. PMID:26163549

  10. Structural, mechanical, and electronic properties of Rh2B and RhB2: first-principles calculations

    PubMed Central

    Chu, Binhua; Li, Da; Tian, Fubo; Duan, Defang; Sha, Xiaojing; Lv, Yunzhou; Zhang, Huadi; Liu, Bingbing; Cui, Tian

    2015-01-01

    The crystal structures of Rh2B and RhB2 at ambient pressure were explored by using the evolutionary methodology. A monoclinic P21/m structure of Rh2B was predicted and donated as Rh2B-I, which is energetically much superior to the previously experimentally proposed Pnma structure. At the pressure of about 39 GPa, the P21/m phase of Rh2B transforms to the C2/m phases. For RhB2, a new monoclinic P21/m phase was predicted, named as RhB2-II, it has the same structure type with Rh2B. Rh2B-I and RhB2-II are both mechanically and dynamically stable. They are potential low compressible materials. The analysis of electronic density of states and chemical bonding indicates that the formation of strong and directional covalent B-B and Rh-B bonds in these compounds contribute greatly to their stabilities and high incompressibility. PMID:26123399

  11. MOLECULAR CHARACTERIZATION OF CYP2B6 SUBSTRATES

    PubMed Central

    Ekins, Sean; Iyer, Manisha; Krasowski, Matthew D.; Kharasch, Evan D.

    2008-01-01

    CYP2B6 has not been as fully characterized at the molecular level as other members of the human cytochrome P450 family. As more widely used in vitro probes for characterizing the involvement of this enzyme in the metabolism of xenobiotics have become available, the number of molecules identified as CYP2B6 substrates has increased. In this study we have analyzed the available kinetic data generated by multiple laboratories with human recombinant expressed CYP2B6 and along with calculated molecular properties derived from the ChemSpider database, we have determined the molecular features that appear to be important for CYP2B6 substrates. In addition we have applied 2D and 3D QSAR methods to generate predictive pharmacophore and 2D models. For 28 molecules with Km data, the molecular weight (mean ± SD) is 253.78±74.03, ACD/logP is 2.68±1.51, LogDpH 5.5 is 1.51±1.43, LogDpH 7.4 is 2.02±1.25, hydrogen bond donor (HBD) count is 0.57 ±0.57, hydrogen bond acceptor (HBA) count is 2.57±1.37, rotatable bonds is 3.50±2.71 and total polar surface area (TPSA) is 27.63±19.42. A second set of 15 molecules without Km data possessed similar mean molecular property values. These properties are comparable to those of a set of 21 molecules used in a previous pharmacophore modeling study (Ekins et al., J Pharmacol Exp Ther 288 (1), 21–29, 1999). Only the LogD and HBD values were statistically significantly different between these different datasets. We have shown that CYP2B6 substrates are generally small hydrophobic molecules that are frequently central nervous system active, which may be important for drug discovery research. PMID:18537573

  12. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo

    PubMed Central

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M.; Werling, Dirk

    2015-01-01

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a “proof of concept” vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. PMID:26476879

  13. Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

    PubMed

    Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

    2015-11-17

    Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. PMID:26476879

  14. Immunogenicity of a West Nile Virus DIII-Cholera Toxin A2/B Chimera after Intranasal Delivery

    PubMed Central

    Tinker, Juliette K.; Yan, Jie; Knippel, Reece J.; Panayiotou, Panos; Cornell, Kenneth A.

    2014-01-01

    West Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA2/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB/c mice were immunized intranasally with DIII-CTA2/B, DIII, DIII mixed with CTA2/B, or CTA2/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA2/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA2/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA2/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA2/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate. PMID:24759174

  15. The ISS 2B PVTCS Ammonia Leak: An Operational History

    NASA Technical Reports Server (NTRS)

    Vareha, Anthony

    2014-01-01

    In 2006, the Photovoltaic Thermal Control System (PVTCS) for the International Space Station's 2B power channel began leaking ammonia at a rate of approximately 1.5lbm/year (out of a starting approximately 53lbm system ammonia mass). Initially, the operations strategy was "feed the leak," a strategy successfully put into action via Extra Vehicular Activity during the STS-134 mission. During this mission the system was topped off with ammonia piped over from a separate thermal control system. This recharge was to have allowed for continued power channel operation into 2014 or 2015, at which point another EVA would have been required. Without these periodic EVAs to refill the 2B coolant system, the channel would eventually leak enough fluid as to risk pump cavitation and system failure, resulting in the loss of the 2B power channel - the most critical of the Space Station's 8 power channels. In mid-2012, the leak rate increased to approximately 5lbm/year. Once discovered, an EVA was planned and executed within a 5 week timeframe to drastically alter the architecture of the PVTCS via connection to a dormant thermal control system not intended to be utilized as anything other than spare components. The purpose of this rerouting of the TCS was to increase system volume and to isolate the photovoltaic radiator, thought to be the likely leak source. This EVA was successfully executed on November 1st, 2012 and left the 2B PVTCS in a configuration where the system was now being adequately cooled via a totally different radiator than what the system was designed to utilize. Unfortunately, data monitoring over the next several months showed that the isolated radiator was not leaking, and the system itself continued to leak steadily until May 9th, 2013. It was on this day that the ISS crew noticed the visible presence of ammonia crystals escaping from the 2B channel's truss segment, signifying a rapid acceleration of the leak from 5lbm/year to 5lbm/day. Within 48 hours of the

  16. Anisotropic elastic and vibrational properties of Ru2B3 and Os2B3: a first-principles investigation

    NASA Astrophysics Data System (ADS)

    Ozisik, Haci; Deligoz, Engin; Surucu, Gokhan; Bogaz Ozisik, Havva

    2016-07-01

    The structural, mechanical and lattice dynamical properties of Ru2B3 and Os2B3 have been investigated by using a first-principles method based on the density functional theory within the generalized gradient approximation. The single crystal elastic constants are numerically estimated using strain–stress approach. The polycrystalline aggregate elastic parameters are calculated from the single elastic constants via the Voigt–Reuss–Hill approximations. Subsequently, the ductility and brittleness are characterized with the estimation from Pugh’s rule (B/G) and Cauchy pressure. Additionally, the Debye temperature is calculated from the average elastic wave velocity obtained from bulk and shear moduli. The calculated parameters are consistent with the previous experimental and theoretical data. These borides are both mechanically and dynamically stable in the considered structure.

  17. Identification of A2B5-positive putative oligodendrocyte progenitor cells and A2B5-positive astrocytes in adult human white matter.

    PubMed

    Scolding, N J; Rayner, P J; Compston, D A

    1999-03-01

    Spontaneous remyelination of previously demyelinated axons is found in a substantial minority of acute and chronic lesions in multiple sclerosis. In the rodent, central remyelination restores saltatory conduction and helps restore limb function, and it seems likely that endogenous myelin repair contributes to neurological recovery in multiple sclerosis. However, the identity of the remyelinating cell remains enigmatic. Fully differentiated oligodendrocytes have very limited capacity for recapitulating their developmental activities and re-engaging myelination pathways. Proliferative oligodendrocyte progenitors--often known as O-2A cells because of their ability to differentiate in vitro into either oligodendrocytes or ("type 2") astrocytes--are, in contrast, extremely efficient at myelin repair either spontaneously, or after transplantation into the de- or dysmyelinated CNS. Oligodendrocyte progenitors are present in both developing and adult rodent CNS. We have previously demonstrated that proliferative oligodendrocyte progenitors are present in cultures prepared from the adult human CNS. Here, using fresh tissue print preparations, we report that cells with processes and the A2B5-positive immunophenotype of proliferative oligodendrocyte progenitors are present in situ in adult human white matter. This technique also reveals the occurrence of A2B5-positive astrocytes, a cell also not previously identified in the normal adult human CNS. In the light of the rodent data showing the importance of oligodendrocyte progenitors in myelin repair, our findings suggesting the presence of progenitors in the adult human brain may have significant implications for spontaneous remyelination in multiple sclerosis and other demyelinating conditions. PMID:10051212

  18. Figures of merit for laser beam quality

    NASA Technical Reports Server (NTRS)

    Milster, T. D.; Walker, E. P.

    1993-01-01

    It was shown how full-width at half maximum (FWHM), full-width at 1/e(sup 2) (FW1/e(sup 2)), Strehl ratio, and encircled energy figures of merit vary with different types of aberration and measurement methods. The array sampling method and the slit-scan method are examined in detail. Our irradiance in the exit pupil of the optical system is a simple gaussian. It was found that in general the slit-scan method and the array method do not yield the same result. The width measurements for the central lobe of the diffraction pattern are very insensitive to aberration.

  19. Noise figure of amplified dispersive Fourier transformation

    SciTech Connect

    Goda, Keisuke; Jalali, Bahram

    2010-09-15

    Amplified dispersive Fourier transformation (ADFT) is a powerful tool for fast real-time spectroscopy as it overcomes the limitations of traditional optical spectrometers. ADFT maps the spectrum of an optical pulse into a temporal waveform using group-velocity dispersion and simultaneously amplifies it in the optical domain. It greatly simplifies spectroscopy by replacing the diffraction grating and detector array in the conventional spectrometer with a dispersive fiber and single-pixel photodetector, enabling ultrafast real-time spectroscopic measurements. Following our earlier work on the theory of ADFT, here we study the effect of noise on ADFT. We derive the noise figure of ADFT and discuss its dependence on various parameters.

  20. Infrared thermal imaging figures of merit

    NASA Technical Reports Server (NTRS)

    Kaplan, Herbert

    1989-01-01

    Commercially available types of infrared thermal imaging instruments, both viewers (qualitative) and imagers (quantitative) are discussed. The various scanning methods by which thermal images (thermograms) are generated will be reviewed. The performance parameters (figures of merit) that define the quality of performance of infrared radiation thermometers will be introduced. A discussion of how these parameters are extended and adapted to define the performance of thermal imaging instruments will be provided. Finally, the significance of each of the key performance parameters of thermal imaging instruments will be reviewed and procedures currently used for testing to verify performance will be outlined.

  1. 75 FR 31324 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2B19 (Regional Jet Series 100 & 440...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3... in the AD docket. Relevant Service Information Bombardier has issued Temporary Revision (TR) 2A-43...-600-2B19 Maintenance Requirements Manual; and Canadair Regional Jet TR RJ/178-1, dated March 8,...

  2. MED23: a new Mediator of H2B monoubiquitylation.

    PubMed

    Streubel, Gundula; Bracken, Adrian P

    2015-12-01

    The Mediator multiprotein complex physically links transcription factors to RNA polymerase II and the basal transcription machinery. While the Mediator complex has been shown to be required for transcriptional initiation and elongation, the understanding of its interplay with histone modifying enzymes and post‐translational modifications remains elusive. In this issue of The EMBO Journal, Yao et al (2015) report that the MED23 subunit of the Mediator complex physically associates with the heterodimeric RNF20/40 E3‐ligase complex to facilitate the monoubiquitylation of histone H2B on gene bodies of actively transcribed genes. PMID:26438725

  3. The Preparation and Characterization of INTEC Phase 2b Composition Variation Study Glasses

    SciTech Connect

    B. A. Staples; B. A. Scholes; L. L. Torres; C. A. Musick; B. R. Boyle; D. K. Peeler; J. D. Vienna

    2000-02-01

    The second phase of the composition variation study (CVS) for the development of glass compositions to immobilize Idaho Nuclear Technology and Engineering Center (INTEC) high level wastes (HLW) is complete. This phase of the CVS addressed waste composition of high activity waste fractions (HAW) from the initial separations flowsheet. Updated estimates if INTEC calcined HLW compositions and of high activity waste fractions proposed to be separated from dissolved calcine were used as the waste component for this CVS phase. These wastes are of particular interest because high aluminum, calcium, zirconium, fluorine, potassium, and low iron and sodium content places them outside the vitrification experience in the Department of Energy complex. Because of the presence of calcium and fluorine, two major zirconia calcine components not addressed in Phase I, a series of scooping tests, designated Phase 2a, were performed. The results of these tests provided information on the effects of calcium and fluoride solubility and their impacts on product properties and composition boundary information for Phase 2b. Details and results of Phase 2a are reported separately. Through application of statistical techniques and the results of Phase 2a, a test matrix was defined for Phase 2b of the CVS. From this matrix, formulations were systematically selected for preparation and characterization with respect to visual and optical homogeneity, viscosity as a function of melt temperature, liquidus temperature (TL), and leaching properties based on response to the product consistency test. The results of preparing and characterizing the Phase 2b glasses are presented in this document. Based on the results, several formulations investigated have suitable properties for further development. A full analysis of the composition-product characteristic relationship of glasses being developed for immobilizing INTEC wastes will be performed at the completion of composition-property relationship

  4. [The endemic goitre in figurative arts].

    PubMed

    Giampalmo, A

    1996-01-01

    For the past fifteen years the author has been collecting photografic documentation of works of figurative arts (graffiti, mosiac, engravings, paintings and sculptures) made at different times and places, in which he found mostly unintentional display of diseases or deformities that would be clearly identified in nosography in the light of today's knowledge. In this study the author intends to illustrate briefly different cases on endemic goitre - whose representation is particularly frequent in figurative arts - in chronological order, beginning with the most ancient ones and focussing on Italian portraying of the Nativity and the Passion of Christ, where the most striking infirmities and disabilities were mirrored and commonly accepted. This study whose interest lies between a scientific and a humanistic one has also importance in the field of art, and especially in relevant philological research which is of particular importance to us pathologists. At last it contribute to establish the epidemiology of some diseases and the knowledge of historical and geographical pathology. PMID:11623474

  5. Interferometer for optical waviness and figure testing

    NASA Astrophysics Data System (ADS)

    Freischlad, Klaus R.

    1997-09-01

    A novel instrument is described for the optical, non-contact measurement of the waviness and figure component of the surface texture of flat surface. Here the spatial frequency range for waviness is typically chosen from 1.25/mm to 0.05/mm, whereas the global figure error contains the lower spatial frequencies. The special requirements on the dynamic range, the spatial resolution, and the signal-to-noise ratio of the measurement are discussed. The presented instrument consists of a white-light, extended-source, phase-shifting Mach-Zehnder interferometer. The special design employing low temporal and spatial coherence avoids coherent speckle noise on the measured surface maps while providing good spatial resolution. Thus in the waviness frequency band the modulation transfer function exceeds 0.75, an the RMS- precision is 0.1nm over the measurement area of 100mm in diameter. Measurement examples of typical applications, e.g. substrates for hard disks and flat panel displays, are shown.

  6. Surface figure control for coated optics

    DOEpatents

    Ray-Chaudhuri, Avijit K.; Spence, Paul A.; Kanouff, Michael P.

    2001-01-01

    A pedestal optical substrate that simultaneously provides high substrate dynamic stiffness, provides low surface figure sensitivity to mechanical mounting hardware inputs, and constrains surface figure changes caused by optical coatings to be primarily spherical in nature. The pedestal optical substrate includes a disk-like optic or substrate section having a top surface that is coated, a disk-like base section that provides location at which the substrate can be mounted, and a connecting cylindrical section between the base and optics or substrate sections. The optic section has an optical section thickness.sup.2 /optical section diameter ratio of between about 5 to 10 mm, and a thickness variation between front and back surfaces of less than about 10%. The connecting cylindrical section may be attached via three spaced legs or members. However, the pedestal optical substrate can be manufactured from a solid piece of material to form a monolith, thus avoiding joints between the sections, or the disk-like base can be formed separately and connected to the connecting section. By way of example, the pedestal optical substrate may be utilized in the fabrication of optics for an extreme ultraviolet (EUV) lithography imaging system, or in any optical system requiring coated optics and substrates with reduced sensitivity to mechanical mounts.

  7. The Amazon Boundary-Layer Experiment (ABLE 2B) - A meteorological perspective

    NASA Technical Reports Server (NTRS)

    Garstang, Michael; Greco, Steven; Scala, John; Swap, Robert; Ulanski, Stanley; Fitzjarrald, David; Martin, David; Browell, Edward; Shipman, Mark; Connors, Vickie

    1990-01-01

    The Amazon Boundary-Layer Experiments (ABLE) 2A and 2B, which were performed near Manaus, Brazil in July-August, 1985, and April-May, 1987 are discussed. The experiments were performed to study the sources, sinks, concentrations, and transports of trace gases and aerosols in rain forest soils, wetlands, and vegetation. Consideration is given the design and preliminary results of the experiment, focusing on the relationships between meteorological scales of motion and the flux, transports, and reactions of chemical species and aerosols embedded in the atmospheric fluid. Meteorological results are presented and the role of the meteorological results in the atmospheric chemistry experiment is examined.

  8. Impact assessment of draft DOE Order 5820.2B. Radioactive Waste Technical Support Program

    SciTech Connect

    1995-04-01

    The Department of Energy (DOE) has prepared a revision to DOE Order 5820.2A, entitled ``Radioactive Waste Management.`` DOE issued DOE Order 5820.2A in September 1988 and, as the title implies, it covered only radioactive waste forms. The proposed draft order, entitled ``Waste Management,`` addresses the management of both radioactive and nonradioactive waste forms. It also includes spent nuclear fuel, which DOE does not consider a waste. Waste forms covered include hazardous waste, high-level waste, transuranic (TRU) waste, low-level radioactive waste, uranium and thorium mill tailings, mixed waste, and sanitary waste. The Radioactive Waste Technical Support Program (TSP) of Leached Idaho Technologies Company (LITCO) is facilitating the revision of this order. The EM Regulatory Compliance Division (EM-331) has requested that TSP estimate the impacts and costs of compliance with the revised order. TSP requested Dames & Moore to aid in this assessment by comparing requirements in Draft Order 5820.2B to ones in DOE Order 5820.2A and other DOE orders and Federal regulations. The assessment started with a draft version of 5820.2B dated January 14, 1994. DOE has released three updated versions of the draft order since then (dated May 20, 1994; August 26, 1994; and January 23, 1995). Each time DOE revised the order, Dames and Moore updated the assessment work to reflect the text changes. This report reflects the January 23, 1995 version of the draft order.

  9. Magnetospheric Multiscale Mission (MMS) Phase 2B Navigation Performance

    NASA Technical Reports Server (NTRS)

    Scaperoth, Paige Thomas; Long, Anne; Carpenter, Russell

    2009-01-01

    The Magnetospheric Multiscale (MMS) formation flying mission, which consists of four spacecraft flying in a tetrahedral formation, has challenging navigation requirements associated with determining and maintaining the relative separations required to meet the science requirements. The baseline navigation concept for MMS is for each spacecraft to independently estimate its position, velocity and clock states using GPS pseudorange data provided by the Goddard Space Flight Center-developed Navigator receiver and maneuver acceleration measurements provided by the spacecraft's attitude control subsystem. State estimation is performed onboard in real-time using the Goddard Enhanced Onboard Navigation System flight software, which is embedded in the Navigator receiver. The current concept of operations for formation maintenance consists of a sequence of two maintenance maneuvers that is performed every 2 weeks. Phase 2b of the MMS mission, in which the spacecraft are in 1.2 x 25 Earth radii orbits with nominal separations at apogee ranging from 30 km to 400 km, has the most challenging navigation requirements because, during this phase, GPS signal acquisition is restricted to less than one day of the 2.8-day orbit. This paper summarizes the results from high-fidelity simulations to determine if the MMS navigation requirements can be met between and immediately following the maintenance maneuver sequence in Phase 2b.

  10. Poetry and the Teaching of Figurative Language Skills.

    ERIC Educational Resources Information Center

    Bush, Harold K., Jr.

    Many teachers note the importance of student ability to analyze and understand intricate uses of figurative language in reading. Research in recent years has focused on the prevalence of figures of speech in textbooks and other reading, suggesting that the fostering of figurative language skills should become a more common feature of language…

  11. Enactivism, Figural Apprehension and Knowledge Objectification: An Exploration of Figural Pattern Generalisation

    ERIC Educational Resources Information Center

    Samson, Duncan; Schafer, Marc

    2011-01-01

    This article explores the inter-relationship between the embodied processes of pattern generalisation and the visualisation of pictorial cues. A research framework is established for analysing pupils' multiple visualisations of figural cues in the context of pattern generalisation. The research framework centres on a novel combination of three…

  12. Figure Control of Lightweight Optical Structures

    NASA Technical Reports Server (NTRS)

    Main, John A.; Song, Haiping

    2005-01-01

    The goal of this paper is to demonstrate the use of fuzzy logic controllers in modifying the figure of a piezoceramic bimorph mirror. Non-contact electron actuation technology is used to actively control a bimorph mirror comprised two PZT-5H wafers by varying the electron flux and electron voltages. Due to electron blooming generated by the electron flux, it is difficult to develop an accurate control model for the bimorph mirror through theoretical analysis alone. The non-contact shape control system with electron flux blooming can be approximately described with a heuristic model based on experimental data. Two fuzzy logic feedback controllers are developed to control the shape of the bimorph mirror according to heuristic fuzzy inference rules generated from previous experimental results. Validation of the proposed fuzzy logic controllers is also discussed.

  13. Precision Segmented Reflector figure control system architecture

    NASA Technical Reports Server (NTRS)

    Mettler, E.; Eldred, D.; Briggs, C.; Kiceniuk, T.; Agronin, M.

    1989-01-01

    A control system architecture for an actively controlled segmented reflector is described along with a design realization for achieving precision alignment of reflector panels. Performance requirements are derived in part from the Large Deployable Reflector, which is a representative mission, and error allocations are made which consider mirror panel surface errors, position measurement and figure estimation, and position control of both quasi-static and dynamic disturbances. The design uses multiple wavelength interferometric edge sensors and voice coil actuators in conjunction with a hybrid control strategy to correct panel position errors. A unit cell shown to be central to the concept is analyzed. The cell integrates the sensing, actuation, and mechanical functions of a control module together with a reflector panel to form a unitized assembly.

  14. Interdependent figure-of-merit software development

    NASA Technical Reports Server (NTRS)

    Ramohalli, K.; Kirsch, T.

    1989-01-01

    This program was undertaken in order to understand the complex nature of interdependent performance in space missions. At the first step in a planned sequence of progress, a spread sheet program was developed to evaluate different fuel/oxidizer combinations for a specific Martian mission. This program is to be linked with output attained using sophisticated software produced by Gordon and McBride. The programming to date makes use of 11 independent parameters. Optimization is essential when faced with the incredible magnitude of costs, risks, and benefits involved with space exploration. A system of weights needs to be devised on which to measure the options. It was the goal to devise a Figure of Merit (FoM) on which different choices can be presented and made. The plan was to model typical missions to Mars, identify the parameters, and vary them until the best one is found. Initially, most of the focus was placed on propellant selection.

  15. Structure analysis for plane geometry figures

    NASA Astrophysics Data System (ADS)

    Feng, Tianxiao; Lu, Xiaoqing; Liu, Lu; Li, Keqiang; Tang, Zhi

    2013-12-01

    As there are increasing numbers of digital documents for education purpose, we realize that there is not a retrieval application for mathematic plane geometry images. In this paper, we propose a method for retrieving plane geometry figures (PGFs), which often appear in geometry books and digital documents. First, detecting algorithms are applied to detect common basic geometry shapes from a PGF image. Based on all basic shapes, we analyze the structural relationships between two basic shapes and combine some of them to a compound shape to build the PGF descriptor. Afterwards, we apply matching function to retrieve candidate PGF images with ranking. The great contribution of the paper is that we propose a structure analysis method to better describe the spatial relationships in such image composed of many overlapped shapes. Experimental results demonstrate that our analysis method and shape descriptor can obtain good retrieval results with relatively high effectiveness and efficiency.

  16. Structure of human nucleosome containing the testis-specific histone variant TSH2B

    SciTech Connect

    Urahama, Takashi; Horikoshi, Naoki; Osakabe, Akihisa; Tachiwana, Hiroaki; Kurumizaka, Hitoshi

    2014-03-25

    The crystal structure of human nucleosome containing the testis-specific TSH2B variant has been determined. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, and induces a local structural difference between TSH2B and H2B in nucleosomes. The human histone H2B variant TSH2B is highly expressed in testis and may function in the chromatin transition during spermatogenesis. In the present study, the crystal structure of the human testis-specific nucleosome containing TSH2B was determined at 2.8 Å resolution. A local structural difference between TSH2B and canonical H2B in nucleosomes was detected around the TSH2B-specific amino-acid residue Ser85. The TSH2B Ser85 residue does not interact with H4 in the nucleosome, but in the canonical nucleosome the H2B Asn84 residue (corresponding to the TSH2B Ser85 residue) forms water-mediated hydrogen bonds with the H4 Arg78 residue. In contrast, the other TSH2B-specific amino-acid residues did not induce any significant local structural changes in the TSH2B nucleosome. These findings may provide important information for understanding how testis-specific histone variants form nucleosomes during spermatogenesis.

  17. Detection of a new cluster of porcine circovirus type 2b strains in domestic pigs in Germany.

    PubMed

    Eddicks, M; Fux, R; Szikora, F; Eddicks, L; Majzoub-Altweck, M; Hermanns, W; Sutter, G; Palzer, A; Banholzer, E; Ritzmann, M

    2015-04-17

    PCV2 can be divided into three different genotypes: PCV2a, PCV2b and PCV2c. Since 2004/2005 PCV2b has become the predominant genotype in the domestic pig population worldwide. In the years 2010 and 2012 PCV2b mutant strains (mPCV2), classified as PCV2b-1C strains, were detected in porcine circovirus diseases (PCVD) affected pigs in China and the United States, respectively. Within one year (April 2013-April 2014) newly emerging mPCV2 strains were isolated in seven German pig farms routinely vaccinating against PCV2. Histopathological, clinical and molecular biological findings including in-situ hybridization (ISH) and real-time PCR indicate PCVD in the affected animals. Characterized isolates from five farms were closely related to the PCV2b-1C reference strain BDH (GenBank no. HM038017), whereas strains from two other farms were only 99.1% and 99.0% identical (based on the nucleotide sequence of the complete genome) to mPCV2 strain BDH, respectively. PMID:25669598

  18. ANKS1B Gene Product AIDA-1 Controls Hippocampal Synaptic Transmission by Regulating GluN2B Subunit Localization

    PubMed Central

    Tindi, Jaafar O.; Chávez, Andrés E.; Cvejic, Svetlana; Calvo-Ochoa, Erika; Castillo, Pablo E.

    2015-01-01

    NMDA receptors (NMDARs) are key mediators of glutamatergic transmission and synaptic plasticity, and their dysregulation has been linked to diverse neuropsychiatric and neurodegenerative disorders. While normal NMDAR function requires regulated expression and trafficking of its different subunits, the molecular mechanisms underlying these processes are not fully understood. Here we report that the amyloid precursor protein intracellular domain associated-1 protein (AIDA-1), which associates with NMDARs and is encoded by ANKS1B, a gene recently linked to schizophrenia, regulates synaptic NMDAR subunit composition. Forebrain-specific AIDA-1 conditional knock-out (cKO) mice exhibit reduced GluN2B-mediated and increased GluN2A-mediated synaptic transmission, and biochemical analyses show AIDA-1 cKO mice have low GluN2B and high GluN2A protein levels at isolated hippocampal synaptic junctions compared with controls. These results are corroborated by immunocytochemical and electrophysiological analyses in primary neuronal cultures following acute lentiviral shRNA-mediated knockdown of AIDA-1. Moreover, hippocampal NMDAR-dependent but not metabotropic glutamate receptor-dependent plasticity is impaired in AIDA-1 cKO mice, further supporting a role for AIDA-1 in synaptic NMDAR function. We also demonstrate that AIDA-1 preferentially associates with GluN2B and with the adaptor protein Ca2+/calmodulin-dependent serine protein kinase and kinesin KIF17, which regulate the transport of GluN2B-containing NMDARs from the endoplasmic reticulum (ER) to synapses. Consistent with this function, GluN2B accumulates in ER-enriched fractions in AIDA-1 cKO mice. These findings suggest that AIDA-1 regulates NMDAR subunit composition at synapses by facilitating transport of GluN2B from the ER to synapses, which is critical for NMDAR plasticity. Our work provides an explanation for how AIDA-1 dysfunction might contribute to neuropsychiatric conditions, such as schizophrenia. PMID:26085624

  19. Study of Subsonic Flow Over a TOW 2B Missile

    NASA Astrophysics Data System (ADS)

    Goudarzi, Koorosh; Jamali, Mehdi

    2016-01-01

    The objective of this investigation is to study the subsonic flow over a missile. In this paper, a model of TOW 2B missile is studied. Two computational approaches are being explored, namely solutions based on the Reynolds-averaged compressible Navier-Stokes equations and solutions based on the inviscid flow (small disturbance theory). The simulations are performed at the Mach number of 0.6, 0.7, 0.8, 0.9 and 1.0 at four angles of attack of 2, 4, 6 and 8 degree. Results obtained from analytical simulation are compared with numerical data. It is found that lift and drag coefficients would go up by increasing of the angle of attack and the Mach number. Trend of changes of the results that obtained from the small disturbance theory is roughly as same as the numeric solution.

  20. Integrated Product and Process Data for B2B Collaboration

    SciTech Connect

    Kulvatunyou, Boonserm; Ivezic, Nenad; Jones, Albert; Wysk, Richard A.

    2003-09-01

    Collaborative development of engineered products in a business-to-business (B2B) environment will require more than just the selection of components from an on-line catalogue. It will involve the electronic exchange of product, process, and production engineering information during both design and manufacturing. While the state-of-the-practice does include a variety of ways to exchange product data electronically, it does not extend to the exchange of manufacturing process data. The reason is simple; process data is usually tied to specific manufacturing resources. These resources are not known typically at product development time. This paper proposes an approach, called an Integrated Product and Process Data (IPPD), where manufacturing process data is considered during product development. This approach replaces traditional process plans, which are resource specific, with a resource-independent process representation. Such a representation will allow a much wider collaboration among business partners and provide the necessary base for collaborative product development.

  1. The cyclotron energization through auroral wave experiments (CENTAUR 2B)

    NASA Technical Reports Server (NTRS)

    Winningham, J. D.

    1992-01-01

    The CENTAUR 2B mission, a dual payload program, is in many aspects the same as the previous missions from Cape Perry and Norway in 1985. It was planned that these payloads would be launched from Andoya, Norway, Nov. 1989 from the Universal II launcher. The payloads are identical, but would have been launched at different azimuths as far north and as far west as possible. Particle experiments include the angular resolving energy analyzer (AREA), the fast ion mass spectrometer (FIMS), the spectrographic particle images (SPI), and finally, the differential ion flux probe (DIFP). SwRI was responsible for the scientific payload, which includes the power supplies, the power supply interfacing, the manipulating of the data from the instruments to format it for the telemetry system, all mechanical structure and restraint mechanisms, and the payload subskin. The status of the various components of this program is given.

  2. Semantic ETL into i2b2 with Eureka!

    PubMed

    Post, Andrew R; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H

    2013-01-01

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns' complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  3. Semantic ETL into i2b2 with Eureka!

    PubMed Central

    Post, Andrew R.; Krc, Tahsin; Rathod, Himanshu; Agravat, Sanjay; Mansour, Michel; Torian, William; Saltz, Joel H.

    Clinical phenotyping is an emerging research information systems capability. Research uses of electronic health record (EHR) data may require the ability to identify clinical co-morbidities and complications. Such phenotypes may not be represented directly as discrete data elements, but rather as frequency, sequential and temporal patterns in billing and clinical data. These patterns’ complexity suggests the need for a robust yet flexible extract, transform and load (ETL) process that can compute them. This capability should be accessible to investigators with limited ability to engage an IT department in data management. We have developed such a system, Eureka! Clinical Analytics. It extracts data from an Excel spreadsheet, computes a broad set of phenotypes of common interest, and loads both raw and computed data into an i2b2 project. A web-based user interface allows executing and monitoring ETL processes. Eureka! is deployed at our institution and is available for deployment in the cloud. PMID:24303265

  4. Doc2b Serves as a Scaffolding Platform for Concurrent Binding of Multiple Munc18 Isoforms in Pancreatic Islet Beta Cells

    PubMed Central

    Ramalingam, Latha; Lu, Jingping; Hudmon, Andy; Thurmond, Debbie C.

    2015-01-01

    Biphasic glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells involves SNARE protein-regulated exocytosis. SNARE complex assembly further requires the regulatory proteins Munc18c, Munc18-1 and Doc2b. Munc18-1 and Munc18c are required for 1st- and 2nd-phase GSIS, respectively. These distinct Munc18-1 and Munc18c roles are related to their transient high-affinity binding with their cognate t-SNAREs; Syntaxin 1A and Syntaxin 4, respectively. Doc2b is essential for both phases of GSIS, yet the molecular basis for this remains unresolved. Because Doc2b binds to Munc18-1 and Munc18c via it’s distinct C2A and C2B domains, respectively, we hypothesized that Doc2b may provide a plasma membrane-localized scaffold/platform for transient docking of these Munc18 isoforms during GSIS. Toward this, macromolecular complexes composed of Munc18c, Doc2b, and Munc18-1 were detected in beta cells. In vitro interaction assays indicated that Doc2b is required to bridge the interaction between Munc18c and Munc18-1 in the macromolecular complex; Munc18c and Munc18-1 failed to associate in the absence of Doc2b. Competition-based GST-Doc2b interaction assays revealed that Doc2b could simultaneously bind both Munc18-1 and Munc18c. Hence, these data support a working model wherein Doc2b functions as a docking platform/scaffold for transient interactions with the multiple Munc18 isoforms operative in insulin release, promoting SNARE assembly. PMID:25190515

  5. A Computer Graphics Human Figure Application Of Biostereometrics

    NASA Astrophysics Data System (ADS)

    Fetter, William A.

    1980-07-01

    A study of improved computer graphic representation of the human figure is being conducted under a National Science Foundation grant. Special emphasis is given biostereometrics as a primary data base from which applications requiring a variety of levels of detail may be prepared. For example, a human figure represented by a single point can be very useful in overview plots of a population. A crude ten point figure can be adequate for queuing theory studies and simulated movement of groups. A one hundred point figure can usefully be animated to achieve different overall body activities including male and female figures. A one thousand point figure si-milarly animated, begins to be useful in anthropometrics and kinesiology gross body movements. Extrapolations of this order-of-magnitude approach ultimately should achieve very complex data bases and a program which automatically selects the correct level of detail for the task at hand. See Summary Figure 1.

  6. A figure control sensor for the Large Deployable Reflector (LDR)

    NASA Technical Reports Server (NTRS)

    Bartman, R.; Dubovitsky, S.

    1988-01-01

    A sensing and control system is required to maintain high optical figure quality in a segmented reflector. Upon detecting a deviation of the segmented surface from its ideal form, the system drives segment mounted actuators to realign the individual segments and thereby return the surface to its intended figure. When the reflector is in use, a set of figure sensors will determine positions of a number of points on the back surface of each of the reflector's segments, each sensor being assigned to a single point. By measuring the positional deviations of these points from previously established nominal values, the figure sensors provide the control system with the information required to maintain the reflector's optical figure. The optical lever, multiple wavelength interferometer, and electronic capacitive sensor, the most promising technologies for the development of the figure sensor, are illustrated. It is concluded that to select a particular implementation of the figure sensors, performance requirement will be refined and relevant technologies investigated further.

  7. Increased binding of circulating systemic lupus erythematosus autoantibodies to recombinant interferon alpha 2b.

    PubMed

    Khan, Wahid Ali; Qureshi, Javed Anwer

    2015-12-01

    Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by various types of immunological abnormalities including circulating and tissue-fixed autoantibodies reactive with autoantigens. The mechanism that can explain the production of these antibodies is unclear. Here we address the binding specificity of SLE autoantibodies with recombinant alpha interferon 2b (hrIFN α-2b), commercially available interferon (IFN α-2b), and the gene (cIFN α-2b) encoding this interferon. hrIFN α-2b showed higher binding with naturally occurring SLE autoantibodies as compared to IFN α-2b (p < 0.05) or cIFN α-2b gene (p < 0.001) as assessed by direct binding, inhibition ELISA, and quantitative precipitin titration. The relative affinity of SLE autoantibodies for hrIFN α-2b, IFN α-2b, and cIFN α-2b gene was in the order of 1.13 × 10(-7) , 1.38 × 10(-6) , and 1.22 × 10(-6) , respectively. hrIFN α-2b is shown to have unique epitopes that would explain the possible antigenic role of hrIFN α-2b in the generation of SLE autoantibodies. Anti-hrIFN α-2b antibodies have been shown to represent an alternative immunological probe for the estimation of interferon alpha 2b in the serum of SLE patients. PMID:26547367

  8. Loss of Arabidopsis thaliana Dynamin-Related Protein 2B Reveals Separation of Innate Immune Signaling Pathways

    PubMed Central

    Smith, John M.; Leslie, Michelle E.; Robinson, Samuel J.; Korasick, David A.; Zhang, Tong; Backues, Steven K.; Cornish, Peter V.; Koo, Abraham J.; Bednarek, Sebastian Y.; Heese, Antje

    2014-01-01

    Vesicular trafficking has emerged as an important means by which eukaryotes modulate responses to microbial pathogens, likely by contributing to the correct localization and levels of host components necessary for effective immunity. However, considering the complexity of membrane trafficking in plants, relatively few vesicular trafficking components with functions in plant immunity are known. Here we demonstrate that Arabidopsis thaliana Dynamin-Related Protein 2B (DRP2B), which has been previously implicated in constitutive clathrin-mediated endocytosis (CME), functions in responses to flg22 (the active peptide derivative of bacterial flagellin) and immunity against flagellated bacteria Pseudomonas syringae pv. tomato (Pto) DC3000. Consistent with a role of DRP2B in Pattern-Triggered Immunity (PTI), drp2b null mutant plants also showed increased susceptibility to Pto DC3000 hrcC−, which lacks a functional Type 3 Secretion System, thus is unable to deliver effectors into host cells to suppress PTI. Importantly, analysis of drp2b mutant plants revealed three distinct branches of the flg22-signaling network that differed in their requirement for RESPIRATORY BURST OXIDASE HOMOLOGUE D (RBOHD), the NADPH oxidase responsible for flg22-induced apoplastic reactive oxygen species production. Furthermore, in drp2b, normal MAPK signaling and increased immune responses via the RbohD/Ca2+-branch were not sufficient for promoting robust PR1 mRNA expression nor immunity against Pto DC3000 and Pto DC3000 hrcC−. Based on live-cell imaging studies, flg22-elicited internalization of the plant flagellin-receptor, FLAGELLIN SENSING 2 (FLS2), was found to be partially dependent on DRP2B, but not the closely related protein DRP2A, thus providing genetic evidence for a component, implicated in CME, in ligand-induced endocytosis of FLS2. Reduced trafficking of FLS2 in response to flg22 may contribute in part to the non-canonical combination of immune signaling defects observed in drp2

  9. A case of figurate urticaria by etanercept.

    PubMed

    Sessa, Maurizio; Sullo, Maria Giuseppa; Mascolo, Annamaria; Cimmaruta, Daniela; Romano, Francesca; Puca, Rosa Valentina; Capuano, Annalisa; Rossi, Francesco; Schiavo, Ada Lo

    2016-01-01

    Etanercept is a competitive inhibitor of tumor necrosis factor-alpha (TNF-α) a polypeptide hormone, involved in the development of the immune system, in host defense and immune surveillance. Even if the etanercept mechanism of action is not completely understood, it is supposed that it negatively modulates biological responses mediated by molecules (cytokines, adhesion molecules, or proteinases) induced or regulated by TNF. For this reason, it is widely used in the treatment of immunologicals diseases, such as rheumatoid and psoriatic arthritis, polyarticular juvenile idiopathic active, ankylosing spondylitis, and plaque psoriasis. Etanercept has a good tolerability profile. Adverse events related to skin are rare, arising usually in about 5% of patients treated with anti-TNF α. In this scenario, we describe a case of figurate urticaria arose after the re-administration of etanercept in a patient affected by psoriasis and hepatitis B. A 65-year-old man, affected by psoriasis, was hospitalized in September 2014 to the Regional Center for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The laboratory analysis detected positivity for hepatitis B virus (HBV) antigens. For this reason, it was administered to him lamivudine 100 mg/die about 30 days before to start etanercept treatment. The etanercept therapy has resulted in a progressive improving of skin manifestations, and the patient decided individually to stop the therapy. Afterwards, for worsening of the psoriatic lesions, he was again hospitalized and treated with the same therapeutic schedule (lamivudine followed by etanercept). Ten days after the start of therapy, the patient showed the onset of urticarial rash. Due to this, the treatment with lamivudine and etanercept was suspended and the patient's clinical conditions improved. It is probably that immunological disorders due to etanercept therapy and HBV infection could

  10. A case of figurate urticaria by etanercept

    PubMed Central

    Sessa, Maurizio; Sullo, Maria Giuseppa; Mascolo, Annamaria; Cimmaruta, Daniela; Romano, Francesca; Puca, Rosa Valentina; Capuano, Annalisa; Rossi, Francesco; Schiavo, Ada Lo

    2016-01-01

    Etanercept is a competitive inhibitor of tumor necrosis factor-alpha (TNF-α) a polypeptide hormone, involved in the development of the immune system, in host defense and immune surveillance. Even if the etanercept mechanism of action is not completely understood, it is supposed that it negatively modulates biological responses mediated by molecules (cytokines, adhesion molecules, or proteinases) induced or regulated by TNF. For this reason, it is widely used in the treatment of immunologicals diseases, such as rheumatoid and psoriatic arthritis, polyarticular juvenile idiopathic active, ankylosing spondylitis, and plaque psoriasis. Etanercept has a good tolerability profile. Adverse events related to skin are rare, arising usually in about 5% of patients treated with anti-TNF α. In this scenario, we describe a case of figurate urticaria arose after the re-administration of etanercept in a patient affected by psoriasis and hepatitis B. A 65-year-old man, affected by psoriasis, was hospitalized in September 2014 to the Regional Center for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The laboratory analysis detected positivity for hepatitis B virus (HBV) antigens. For this reason, it was administered to him lamivudine 100 mg/die about 30 days before to start etanercept treatment. The etanercept therapy has resulted in a progressive improving of skin manifestations, and the patient decided individually to stop the therapy. Afterwards, for worsening of the psoriatic lesions, he was again hospitalized and treated with the same therapeutic schedule (lamivudine followed by etanercept). Ten days after the start of therapy, the patient showed the onset of urticarial rash. Due to this, the treatment with lamivudine and etanercept was suspended and the patient's clinical conditions improved. It is probably that immunological disorders due to etanercept therapy and HBV infection could

  11. The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo.

    PubMed

    Mackler, J M; Drummond, J A; Loewen, C A; Robinson, I M; Reist, N E

    2002-07-18

    Synaptotagmin is a synaptic vesicle protein that is postulated to be the Ca(2+) sensor for fast, evoked neurotransmitter release. Deleting the gene for synaptotagmin (syt(null)) strongly suppresses synaptic transmission in every species examined, showing that synaptotagmin is central in the synaptic vesicle cycle. The cytoplasmic region of synaptotagmin contains two C(2) domains, C(2)A and C(2)B. Five, highly conserved, acidic residues in both the C(2)A and C(2)B domains of synaptotagmin coordinate the binding of Ca(2+) ions, and biochemical studies have characterized several in vitro Ca(2+)-dependent interactions between synaptotagmin and other nerve terminal molecules. But there has been no direct evidence that any of the Ca(2+)-binding sites within synaptotagmin are required in vivo. Here we show that mutating two of the Ca(2+)-binding aspartate residues in the C(2)B domain (D(416,418)N in Drosophila) decreased evoked transmitter release by >95%, and decreased the apparent Ca(2+) affinity of evoked transmitter release. These studies show that the Ca(2+)-binding motif of the C(2)B domain of synaptotagmin is essential for synaptic transmission. PMID:12110842

  12. 5-HT2B receptor-mediated calcium release from ryanodine-sensitive intracellular stores in human pulmonary artery endothelial cells.

    PubMed Central

    Ullmer, C.; Boddeke, H. G.; Schmuck, K.; Lübbert, H.

    1996-01-01

    1. We have characterized the 5-hydroxytryptamine (5-HT)-induced calcium signalling in endothelial cells from the human pulmonary artery. Using RT-PCR we show, that of all cloned G-protein coupled 5-HT receptors, these cells express only 5-HT1D beta, 5-HT2B and little 5-HT4 receptor mRNA. 2. In endothelial cells 5-HT inhibits the formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) via 5-HT1D beta receptors but fails to activate phosphoinositide (PI) turnover. However, the latter pathway is strongly activated by histamine. 3. Despite the lack of detectable inositol phosphate (IP) formation in human pulmonary artery endothelial cells, 5-HT (pD2 = 5.82 +/- 0.06, n = 6) or the selective 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (pD2 = 5.66 +/- 0.03, n = 7) elicited transient calcium signals comparable to those evoked by histamine (pD2 = 6.44 +/- 0.01, n = 7). Since 5-HT2A and 5-HT2C receptor mRNAs are not detectable in pulmonary artery endothelial cells, activation of 5-HT2B receptors is responsible for the transient calcium release. The calcium transients are independent of the inhibition of adenylate cyclase, since DOI does not stimulate 5-HT1D beta receptors. 4. Both, the 5-HT- and histamine-stimulated calcium signals were also observed when the cells were placed in calcium-free medium. This indicates that 5-HT triggers calcium release from intracellular stores. 5. Heparin is an inhibitor of the IP3-activated calcium release channels on the endoplasmic reticulum. Intracellular infusion of heparin through patch pipettes in voltage clamp experiments failed to block 5-HT-induced calcium signals, whereas it abolished the histamine response. This supports the conclusion that the 5-HT-induced calcium release is independent of IP3 formation. 6. Unlike the histamine response, the 5-HT response was sensitive to micromolar concentrations of ryanodine and, to a lesser extent, ruthenium red. This implies that 5-HT2B receptors trigger calcium

  13. An economics figure of merit in ALPS

    SciTech Connect

    Shatilla, Y.A.

    2000-07-01

    One of the most pressing issues facing the deregulated nuclear electric power industry is its economic competitiveness when compared to other sources of electrical power. Traditionally, finding the optimum loading pattern (LP) that meets all the safety and operational objective functions and at the same time produces the most attractive economical solutions is an iterative process. This is because (a) LP search tools usually lack the capability to generate equilibrium solutions and (b) economics objective functions are hard to include in the search process. In this paper, the Westinghouse Advanced Loading Pattern Search code (ALPS) has been demonstrated to successfully find LPs that meet user-defined operational and safety as well as economics objectives. This has been made possible by the development of TULIP language that allows the integration of external procedures into the search process of the main program, ALPS. In the example given, an economic figure of merit (EFM) has been defined and included via TULIP script into the fuel management optimization problem of a three-loop Westinghouse core operating an 18-month cycle. The LPs found by ALPS exhibit a clear trend of meeting and, in some cases, exceeding the EFM objective function defined for the ALPS search process a priori.

  14. Figure skater level moderates balance training.

    PubMed

    Saunders, N W; Hanson, N J; Koutakis, P; Chaudhari, A M; Devor, S T

    2013-04-01

    It was suggested that baseline levels of postural control in figure skaters might influence the effectiveness of neuromuscular training. The aims of the present study were to investigate the baseline association of skater skill level with standard center of pressure metrics and time to stabilization, and to determine if skill level influenced the effectiveness of a 6-week neuromuscular training program. There was no main effect of skill level for any baseline center of pressure metric for either test. There was no main effect of skill level on the percent change in any metric for the single leg stance following training. However, skill level did influence landing test outcome measures. The difference in percent change of root mean squared was evident for the mediolateral (low: 24.5±16.50% vs. high: 2.42±14.99%) and anterior-posterior (low: 6.66±9.21% vs. high: - 4.03±5.91%) axes. Percent change in anterior-posterior time to stabilization also differed by skill level (low: - 0.73%±4.74 vs. high: - 5.61%±2.76). Note that this study was underpowered with 26 subjects and 14 subjects contributing to baseline and post-training assessments, respectively. Though no baseline differences in postural control were observed, compared with low skill levels, high skill levels benefitted more from training. PMID:23184479

  15. Resolving the formation of modern Chladni figures

    NASA Astrophysics Data System (ADS)

    Tuan, P. H.; Tung, J. C.; Liang, H. C.; Chiang, P. Y.; Huang, K. F.; Chen, Y. F.

    2015-09-01

    The resonant spectrum of a thin plate driven with a mechanical oscillator is precisely measured to distinguish modern Chladni figures (CFs) observed at the resonant frequencies from classical CFs observed at the non-resonant frequencies. Experimental results reveal that modern CFs generally display an important characteristic of avoided crossings of nodal lines, whereas the nodal lines of classical CFs form a regular grid. The formation of modern CFs and the resonant frequency spectrum are resolved with a theoretical model that characterizes the interaction between the plate and the driving source into the inhomogeneous Kirchhoff-Love equation. The derived formula for determining resonant frequencies is shown to be exactly identical to the meromorphic function given in singular billiards that deals with the coupling strength on the transition between integrable and chaotic features. The good agreement between experimental results and theoretical predictions verifies the significant role of the strong-coupling effect in the formation of modern CFs. More importantly, it is confirmed that the apparatus for generating modern CFs can be developed to serve as an expedient system for exploring the nodal domains of chaotic wave functions as well as the physics of the strong coupling with a point scatterer.

  16. Figuring the Acceleration of the Simple Pendulum

    NASA Astrophysics Data System (ADS)

    Lieberherr, Martin

    2011-12-01

    The centripetal acceleration has been known since Huygens' (1659) and Newton's (1684) time.1,2 The physics to calculate the acceleration of a simple pendulum has been around for more than 300 years, and a fairly complete treatise has been given by C. Schwarz in this journal.3 But sentences like "the acceleration is always directed towards the equilibrium position" beside the picture of a swing on a circular arc can still be found in textbooks, as e.g. in Ref. 4. Vectors have been invented by Grassmann (1844)5 and are conveniently used to describe the acceleration in curved orbits, but acceleration is more often treated as a scalar with or without sign, as the words acceleration/deceleration suggest. The component tangential to the orbit is enough to deduce the period of the simple pendulum, but it is not enough to discuss the forces on the pendulum, as has been pointed out by Santos-Benito and A. Gras-Marti.6 A suitable way to address this problem is a nice figure with a catch for classroom discussions or homework. When I plotted the acceleration vectors of the simple pendulum in their proper positions, pictures as in Fig. 1 appeared on the screen. The endpoints of the acceleration vectors, if properly scaled, seemed to lie on a curve with a familiar shape: a cardioid. Is this true or just an illusion?

  17. Advances in precision mirror figure metrology (abstract)

    SciTech Connect

    Takacs, P.Z.; Furenlid, K. ); Church, E.L. )

    1992-01-01

    New developments in optical measurement techniques have made it possible to test the surface quality on grazing incidence optics with extreme precision and accuracy. An instrument developed at Brookhaven, the Long Trace Profiler (LTP), measures the figure of large (up to 1 m long) cylindrical aspheres with nanometer accuracy. The LTP optical system is based around a common-path interferometer design belonging to the class of slope measuring interferometers and, as such, it is very robust, stable, and vibration insensitive. A unique error correction technique removes the effect of tilt errors in the optical head as it traverses the air bearing, thus allowing one to accurately measure the absolute surface profile and radius of curvature. This is of critical importance to the manufacture of long-radius spherical optics used in high-resolution soft x-ray monochromators and in the testing of mirror bending systems. This talk will review the principle of operation of the LTP, probe the factors limiting the performance of the system, and will examine the current state of the art in synchrotron radiation mirror manufacturing quality (as viewed by our metrology techniques). This research was supported by the U.S. Department of Energy Contract No. DE-AC02-76CH00016.

  18. 2008 Alzheimer's disease facts and figures.

    PubMed

    2008-03-01

    Alzheimer's disease is the seventh leading cause of all deaths in the United States and the fifth leading cause of death in Americans older than the age of 65 years. More than 5 million Americans are estimated to have Alzheimer's disease. Every 71 seconds someone in America develops Alzheimer's disease; by 2050 it is expected to occur every 33 seconds. During the coming decades, baby boomers are projected to add 10 million people to these numbers. By 2050, the incidence of Alzheimer's disease is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million persons. Significant cost implications related to Alzheimer's disease and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (eg, caregiver lost wages and out-of-pocket expenses, decreased business productivity) costs. Not included in these figures are the estimated 10 million caregivers who annually provide $89 billion in unpaid services to individuals with Alzheimer's disease. This report provides information to increase understanding of the public health impact of Alzheimer's disease, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. PMID:18631956

  19. Upregulation of UGT2B4 Expression by 3′-Phosphoadenosine-5′-Phosphosulfate Synthase Knockdown: Implications for Coordinated Control of Bile Acid Conjugation

    PubMed Central

    Barrett, Kathleen G.; Fang, Hailin; Cukovic, Daniela; Dombkowski, Alan A.; Kocarek, Thomas A.

    2015-01-01

    During cholestasis, the bile acid–conjugating enzymes, SULT2A1 and UGT2B4, work in concert to prevent the accumulation of toxic bile acids. To understand the impact of sulfotransferase deficiency on human hepatic gene expression, we knocked down 3′-phosphoadenosine-5′-phosphosulfate synthases (PAPSS) 1 and 2, which catalyze synthesis of the obligate sulfotransferase cofactor, in HepG2 cells. PAPSS knockdown caused no change in SULT2A1 expression; however, UGT2B4 expression increased markedly (∼41-fold increase in UGT2B4 mRNA content). Knockdown of SULT2A1 in HepG2 cells also increased UGT2B4 expression. To investigate the underlying mechanism, we transfected PAPSS-deficient HepG2 cells with a luciferase reporter plasmid containing ∼2 Kb of the UGT2B4 5′-flanking region, which included a response element for the bile acid–sensing nuclear receptor, farnesoid X receptor (FXR). FXR activation or overexpression increased UGT2B4 promoter activity; however, knocking down FXR or mutating or deleting the FXR response element did not significantly decrease UGT2B4 promoter activity. Further evaluation of the UGT2B4 5′-flanking region indicated the presence of distal regulatory elements between nucleotides −10090 and −10037 that negatively and positively regulated UGT2B4 transcription. Pulse-chase analysis showed that increased UGT2B4 expression in PAPSS-deficient cells was attributable to both increased mRNA synthesis and stability. Transfection analysis demonstrated that the UGT2B4 3′-untranslated region decreased luciferase reporter expression less in PAPSS-deficient cells than in control cells. These data indicate that knocking down PAPSS increases UGT2B4 transcription and mRNA stability as a compensatory response to the loss of SULT2A1 activity, presumably to maintain bile acid–conjugating activity. PMID:25948711

  20. Acquired von Willebrand syndrome with a type 2B phenotype: diagnostic and therapeutic dilemmas.

    PubMed

    Scepansky, Ellen; Othman, Maha; Smith, Hedy

    2014-01-01

    In this report, we provide evidence of an acquired von Willebrand syndrome (AVWS) with a type 2B phenotype rather than the expected type 1 or 2A. The patient was referred prior to surgical removal of a fibrous mass within the maxillary sinus. His first bleeding 7 years earlier following a retinal tear had been complicated by monocular blindness. Several mucocutanous bleedings followed. Hematological investigations revealed von Willebrand factor (VWF):Ag 91 IU/ml, factor VIII 86 IU/ml, VWF:RCo 34 IU/ml and profound thrombocytopenia with platelet clumping. VWF multimer analysis showed a loss of high-molecular-weight multimers and his plasma aggregated normal platelets under low ristocetin concentration, consistent with type 2B von Willebrand disease (VWD). Sequencing of VWF exon 28 and of the platelet GP1BA gene to investigate the possibility of platelet-type VWD failed to reveal mutations. Serum protein electrophoresis showed a monoclonal IgG protein and led to the diagnosis of monoclonal gammopathy of unknown significance (MGUS), raising suspicion of an AVWS. Over 2 years, he experienced severe gingival bleedings and traumatic intracerebral hemorrhage. Following debridement of the sinus mass, the patient required 20 units of packed red blood cells, despite high-dose Humate-P, continuous Amicar and twice-daily platelet transfusions. Bleeding finally ceased following infusion of activated factor VIIa. A history of prior uncomplicated vasectomy and tendon laceration, no family history of bleeding, the inability to identify a causative mutation in either exon 28 VWF or platelet GP1BA and the MGUS led to diagnosis of AVWS with a type 2B phenotype. This case highlights the difficulties in assigning a diagnosis and the management of bleeding in a patient with an atypical presentation of AVWS. PMID:24296552

  1. Molecular characterization of an. alpha. sub 2B -adrenergic receptor

    SciTech Connect

    Harrison, J.K.; Dewan Zeng; D'Angelo, D.D.; Tucker, A.L.; Zhihong Lu; Barber, C.M.; Lynch, K.R. )

    1990-02-26

    {alpha}{sub 2}-Adrenergic receptors comprise a heterogeneous population based on pharmacologic and molecular evidence. The authors have isolated a cDNA clone (pRNG{alpha}2) encoding a previously undescribed third subtype of an {alpha}{sub 2}-adrenergic receptor from a rat kidney cDNA library. The library was screened with an oligonucleotide encoding a highly conserved region found in all biogenic amine receptors described to date. The deduced amino acid sequence displays many features of G-protein coupled receptors with exception of the absence of the consensus N-linked glycosylation site at the amino terminus. Membranes prepared from COS-1 cells transfected with pRNG{alpha}2 display high affinity and saturable binding to {sup 3}H-rauwolscine (K{sub d}=2 nM).Competition curve data analysis shows that pRNG{alpha}2 protein binds to a variety of adrenergic drugs with the following rank order of potency: yohimbine {ge} cholorpromazine > prazosin {ge} clonidine > norepinephrine {ge} oxymetazoline. pRNG{alpha}2 RNA accumulates in both adult rat kidney and rat neonatal lung (predominant species is 4.0 kb). They conclude that pRNG{alpha}2 likely represents a cDNA for the {alpha}{sub 2B}-adrenergic receptor.

  2. BRI2 (ITM2b) Inhibits Aβ Deposition in Vivo

    PubMed Central

    Kim, Jungsu; Miller, Victor M.; Levites, Yona; West, Karen Jansen; Zwizinski, Craig W.; Moore, Brenda D.; Troendle, Fredrick J.; Bann, Maralyssa; Verbeeck, Christophe; Price, Robert W.; Smithson, Lisa; Sonoda, Leilani; Wagg, Kayleigh; Rangachari, Vijayaraghavan; Zou, Fanggeng; Younkin, Steven G.; Graff-Radford, Neill; Dickson, Dennis; Rosenberry, Terrone; Golde, Todd E.

    2008-01-01

    Analyses of the biologic effects of mutations in the BRI2 (ITM2b) and the amyloid β precursor protein (APP) genes support the hypothesis that cerebral accumulation of amyloidogenic peptides in familial British and familial Danish dementias and Alzheimer’s disease (AD) is associated with neurodegeneration. We have used somatic brain transgenic technology to express the BRI2 and BRI2-Aβ1-40 transgenes in amyloid β protein precursor (APP) mouse models. Expression of BRI2-Aβ1-40 mimics the suppressive effect previously observed using conventional transgenic methods, further validating the somatic brain transgenic methodology. Unexpectedly, we also find that expression of wild type human BRI2 reduces cerebral Aβ deposition in an AD mouse model. Additional data indicate that the 23 amino acid peptide, Bri23, released from BRI2 by normal processing is present in human cerebrospinal fluid (CSF), inhibits Aβ aggregation in vitro, and mediates its anti-amyloidogenic effect in vivo. These studies demonstrate that BRI2 is a novel mediator of Aβ deposition in vivo. PMID:18524908

  3. Remission of liver fibrosis by interferon-alpha 2b.

    PubMed

    Moreno, M G; Muriel, P

    1995-08-01

    Fibrosis is a dynamic process associated with the continuous deposition and resorption of connective tissue, mainly collagen. Therapeutic strategies are emerging by which this dynamic process can be modulated. Since interferons are known to inhibit collagen production, the aim of this study was to investigate if the administration of interferon-alpha 2b (IFN-alpha) can restore the normal hepatic content of collagen in rats with established fibrosis. Fibrosis was induced by prolonged bile duct ligation. IFN-alpha (100,000 IU/rat/day; s.c.) was administered to fibrotic rats for 15 days. Bile duct ligation increased liver collagen content 6-fold. In addition, serum and liver markers of hepatic injury increased significantly; liver histology showed an increase in collagen deposition, and the normal architecture was lost, with large zones of necrosis being observed frequently. IFN-alpha administration reversed to normal the values of all the biochemical markers measured and restored the normal architecture of the liver. Our results demonstrated that IFN-alpha is useful in reversing fibrosis and liver damage induced by biliary obstruction in the rat. However, further investigations are required to evaluate the therapeutic relevance of interferons on non-viral fibrosis and cholestasis. PMID:7646558

  4. Specific involvement of postsynaptic GluN2B-containing NMDA receptors in the developmental elimination of corticospinal synapses

    PubMed Central

    Ohno, Takae; Maeda, Hitoshi; Murabe, Naoyuki; Kamiyama, Tsutomu; Yoshioka, Noboru; Mishina, Masayoshi; Sakurai, Masaki

    2010-01-01

    The GluN2B (GluRε2/NR2B) and GluN2A (GluRε1/NR2A) NMDA receptor (NMDAR) subtypes have been differentially implicated in activity-dependent synaptic plasticity. However, little is known about the respective contributions made by these two subtypes to developmental plasticity, in part because studies of GluN2B KO [Grin2b−/− (2b−/−)] mice are hampered by early neonatal mortality. We previously used in vitro slice cocultures of rodent cerebral cortex (Cx) and spinal cord (SpC) to show that corticospinal (CS) synapses, once present throughout the SpC, are eliminated from the ventral side during development in an NMDAR-dependent manner. To study subtype specificity of NMDAR in this developmental plasticity, we cocultured Cx and SpC slices derived from postnatal day 0 (P0) animals with different genotypes [2b−/−, Grin2a−/− (2a−/−), or WT mice]. The distribution of CS synapses was studied electrophysiologically and with a voltage-sensitive dye. Synapse elimination on the ventral side was blocked in WT(Cx)-2b−/−(SpC) pairs but not in WT(Cx)-2a−/−(SpC) or 2b−/−(Cx)-WT(SpC) pairs. CS axonal regression was also observed through live imaging of CS axons labeled with enhanced yellow fluorescent protein (EYFP) through exo utero electroporation. These findings suggest that postsynaptic GluN2B is selectively involved in CS synapse elimination. In addition, the elimination was not blocked in 2a−/− SpC slices, where Ca2+ entry through GluN2B-mediated CS synaptic currents was reduced to the same level as in 2b−/− slices, suggesting that the differential effect of GluN2B and GluN2A in CS synapse elimination might not be explained based solely on greater Ca2+ entry through GluN2B-containing channels. PMID:20696923

  5. Click Dehydrogenation of Carbon-Substituted nido-5,6-C2B8H12 Carboranes: A General Route to closo-1,2-C2B8H10 Derivatives.

    PubMed

    Tok, Oleg L; Bakardjiev, Mario; Štíbr, Bohumil; Hnyk, Drahomír; Holub, Josef; Padělková, Zdenka; Růžička, Aleš

    2016-09-01

    Triethylamine-catalyzed dehydrogenation of carbon-disubstituted dicarbaboranes 5,6-R2-nido-5,6-C2B8H10 [1, where R = H (1a), Me (1b), and Ph (1c)] in refluxing acetonitrile leads to a high-yield (up to 85-95%) formation of a series of dicarbaboranes 1,2-R2-closo-1,2-C2B8H8 (2). The monosubstituted 6-R-nido-5,6-C2B8H11 (3) analogues [where R = Ph (3a), naph (1-naphthyl; 3b), Bu (3c)] afforded 1-R-1,2-closo C2B8H9 (4) isomers [where R = Ph (4a), naph (4b), n-Bu (4c)] as the main products; compounds 4a and 4c were accompanied by 2-R-1,2-C2B8H9 (5) isomers (total yields up to 90%), with the 4/5 molar ratio being strongly dependent on the nature of R (4:1 and 1:1, respectively). All of these cage-closure reactions are supposed to proceed via the stage of the corresponding Et3NH(+) salts of nido anions [5,6-R2-5,6-C2B8H9](-) (1(-)) and [6-R-5,6-C2B8H10](-) (3(-)), which lose H2 and Et3N upon heating (dehydrodeamination). The cage-closure mechanisms leading to closo isomers 2, 4, and 5 have been substantiated by B3LYP/6-31+G* calculations of the reaction profile for a simple 1a(-) → 2a + H(-) conversion. All of the compounds isolated have been characterized by multinuclear ((11)B, (1)H, and (13)C) NMR spectroscopy, mass spectrometry, and elemental analyses, and the structure of 1-Ph-closo-1,2-C2B8H9 (4a) was established by an X-ray diffraction study. PMID:27551885

  6. [Obtaining and characteristics of domestic preparation interferon alpha-2b with prolonged effect].

    PubMed

    Pokholenko, Ia A; Porubleva, L V; Dubeĭ, I Ia; Rebriev, A V; Sutugina, L P; Gromovoĭ, T Iu; Pokrovskiĭ, V A; Obolenskaia, M Iu; Chernykh, S I

    2008-01-01

    Pegylated interferon alpha-2b (PEG-IFN alpha-2b) is a domestic preparation of a modified recombinant interferon alpha-2b with prolonged effect. The preparation was obtained by N-terminal pegylation of IFN alpha-2b with polyethylene glycol (PEG). This paper presents the method of PEG-IFN alpha-2b synthesis and characteristics of the obtained product. PAAG electrophoresis, Western blot analysis and MALDI-TOF mass-spectrometry confirm that the preparation is an N-terminal pegylated IFN alpha-2b that contains no more than 10% of dipegylated IFN alpha-2b. The comparison of PEG-IFN alpha-2b with its foreign analogue has revealed the similarity of their biological activity and pharmacokinetic parameters. PMID:19351063

  7. Lighting, backlighting and watercolor illusions and the laws of figurality.

    PubMed

    Pinna, Baingio; Reeves, Adam

    2006-01-01

    We report some novel 'lighting' and 'backlighting' effects in plane figures similar to those which induce the 'watercolor illusion', that is, figures made with outlines composed of juxtaposed parallel lines varying in brightness and chromatic color. These new effects show 'illumination' as an emergent percept, and show how arrangements of 'dark and light' along the boundaries of various plane figures model the volume and strengthen the illusion of depth. To account for these various effects we propose several phenomenological 'laws of figurality' to add to the Gestalt laws of organization and figure-ground segregation. We offer a set of meta-laws which are speculative but which serve to integrate and organize the phenomenological laws. These laws indicate how luminance gradient profiles across boundary contours define both the 3D appearance of figures and the properties of the light reflected from their volumetric shapes. PMID:16862844

  8. 2009 Alzheimer's disease facts and figures.

    PubMed

    2009-05-01

    Alzheimer's disease (AD) is the sixth leading cause of all deaths in the United States, and the fifth leading cause of death in Americans aged 65 and older. Whereas other major causes of death have been on the decrease, deaths attributable to AD have been rising dramatically. Between 2000 and 2006, heart-disease deaths decreased nearly 12%, stroke deaths decreased 18%, and prostate cancer-related deaths decreased 14%, whereas deaths attributable to AD increased 47%. An estimated 5.3 million Americans have AD; the approximately 200,000 persons under age 65 years with AD comprise the younger-onset AD population. Every 70 seconds, someone in America develops AD; by 2050, this time is expected to decrease to every 33 seconds. Over the coming decades, the "baby-boom" population is projected to add 10 million people to these numbers. In 2050, the incidence of AD is expected to approach nearly a million people per year, with a total estimated prevalence of 11 to 16 million people. Significant cost implications related to AD and other dementias include an estimated $148 billion annually in direct (Medicare/Medicaid) and indirect (e.g., decreased business productivity) costs. Not included in these figures is the $94 billion in unpaid services to individuals with AD provided annually by an estimated 10 million caregivers. Mild cognitive impairment (MCI) is an important component in the continuum from healthy cognition to dementia. Understanding which individuals with MCI are at highest risk for eventually developing AD is key to our ultimate goal of preventing AD. This report provides information meant to increase an understanding of the public-health impact of AD, including incidence and prevalence, mortality, lifetime risks, costs, and impact on family caregivers. This report also sets the stage for a better understanding of the relationship between MCI and AD. PMID:19426951

  9. Functional characterization of cytochromes P450 2B from the desert woodrat Neotoma lepida

    PubMed Central

    Wilderman, P. Ross; Jang, Hyun-Hee; Malenke, Jael R.; Salib, Mariam; Angermeier, Elizabeth; Lamime, Sonia; Dearing, M. Denise; Halpert, James R.

    2014-01-01

    Mammalian detoxification processes have been the focus of intense research, but little is known about how wild herbivores process plant secondary compounds, many of which have medicinal value or are drugs. cDNA sequences that code for three enzymes of the cytochrome P450 (CYP) 2B subfamily, here termed 2B35, 2B36, and 2B37 have been recently identified from a wild rodent, the desert woodrat (Malenke et al., 2012). Two variant clones of each enzyme were engineered to increase protein solubility and to facilitate purification, as reported for CYP2B enzymes from multiple species. When expressed in E. coli each of the woodrat proteins gave the characteristic maximum at 450 nm in a reduced carbon monoxide difference spectrum but generally expressed at lower levels than rat CYP2B1. Two enzymes, 2B36 and 2B37, showed dealkylation activity with the model substrates 7-ethoxy-4-(trifluoromethyl)coumarin and 7-benzyloxyresorufin, whereas 2B35 was inactive. Binding of the monoterpene (+)-α-pinene produced a Type I shift in the absorbance spectrum of each enzyme. Mutation of 2B37 at residues 114, 262, or 480, key residues governing ligand interactions with other CYP2B enzymes, did not significantly change expression levels or produce the expected functional changes. In summary, two catalytic and one ligand-binding assay are sufficient to distinguish among CYP2B35, 2B36, and 2B37. Differences in functional profiles between 2B36 and 2B37 are partially explained by changes in substrate recognition site residue 114, but not 480. The results advance our understanding of the mechanisms of detoxification in wild mammalian herbivores and highlight the complexity of this system. PMID:24361551

  10. Beyond the exchange--the future of B2B.

    PubMed

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important. PMID:11184979

  11. Maintenance therapy with interferon alfa 2b in Hodgkin's disease.

    PubMed

    Avilés, A; Díaz-Maqueo, J C; Talavera, A; Nambo, M J; García, E L

    1998-08-01

    We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease. PMID:9711927

  12. Beyond captions: linking figures with abstract sentences in biomedical articles.

    PubMed

    Bockhorst, Joseph P; Conroy, John M; Agarwal, Shashank; O'Leary, Dianne P; Yu, Hong

    2012-01-01

    Although figures in scientific articles have high information content and concisely communicate many key research findings, they are currently under utilized by literature search and retrieval systems. Many systems ignore figures, and those that do not typically only consider caption text. This study describes and evaluates a fully automated approach for associating figures in the body of a biomedical article with sentences in its abstract. We use supervised methods to learn probabilistic language models, hidden Markov models, and conditional random fields for predicting associations between abstract sentences and figures. Three kinds of evidence are used: text in abstract sentences and figures, relative positions of sentences and figures, and the patterns of sentence/figure associations across an article. Each information source is shown to have predictive value, and models that use all kinds of evidence are more accurate than models that do not. Our most accurate method has an F1-score of 69% on a cross-validation experiment, is competitive with the accuracy of human experts, has significantly better predictive accuracy than state-of-the-art methods and enables users to access figures associated with an abstract sentence with an average of 1.82 fewer mouse clicks. A user evaluation shows that human users find our system beneficial. The system is available at http://FigureItOut.askHERMES.org. PMID:22815711

  13. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  14. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  15. 40 CFR Table 2b to Subpart E of... - Reactivity Factors for Aliphatic Hydrocarbon Solvent Mixtures

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Hydrocarbon Solvent Mixtures 2B Table 2B to Subpart E of Part 59 Protection of Environment ENVIRONMENTAL... Hydrocarbon Solvent Mixtures Bin Averageboiling point* (degrees F) Criteria Reactivityfactor (g O3/g VOC) 1 80... Point + Dry Point)/2(b) Aromatic Hydrocarbon Solvents...

  16. 14 CFR 250.2b - Carriers to request volunteers for denied boarding.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Carriers to request volunteers for denied boarding. 250.2b Section 250.2b Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS OVERSALES § 250.2b Carriers to request volunteers for...

  17. Figures and First Years: Examining first-year Calculus I student ability to incorporate figures into technical reports

    NASA Astrophysics Data System (ADS)

    Antonacci, Nathan; Rogers, Michael; Pfaff, Thomas

    This three-year study focused on first-year Calculus I students and their abilities to incorporate figures into technical reports. Students were handed guidelines as part of their Multidisciplinary Sustainability Education Module meant to aid them in crafting effective figures. Figure-specific questionnaires were added in the class to gain insight into the quantitative literacy skills students possessed both before starting their course and after its completion. Reviews of the figures in 78 technical reports written by 106 students showed repeated failure to refer to figures in discussion sections and use them in evidence-based arguments. Analysis of quantitative literacy skills revealed that the students could both read and interpret figures, suggesting that issues with literacy were not the main contributor to the sub-par graphs.

  18. BOOK REVIEW: Relativistic Figures of Equilibrium

    NASA Astrophysics Data System (ADS)

    Mars, M.

    2009-08-01

    Compact fluid bodies in equilibrium under its own gravitational field are abundant in the Universe and a proper treatment of them can only be carried out using the full theory of General Relativity. The problem is of enormous complexity as it involves two very different regimes, namely the interior and the exterior of the fluid, coupled through the surface of the body. This problem is very challenging both from a purely theoretical point of view, as well as regarding the obtaining of realistic models and the description of their physical properties. It is therefore an excellent piece of news that the book 'Relativistic Figures of Equilibrium' by R Meinel, M Ansorg, A Kleinwächter, G Neugebauer and D Petroff has been recently published. This book approaches the topic in depth and its contents will be of interest to a wide range of scientists working on gravitation, including theoreticians in general relativity, mathematical physicists, astrophysicists and numerical relativists. This is an advanced book that intends to present some of the present-day results on this topic. The most basic results are presented rather succinctly, and without going into the details, of their derivations. Although primarily not intended to serve as a textbook, the presentation is nevertheless self-contained and can therefore be of interest both for experts on the field as well as for anybody wishing to learn more about rotating self-gravitating compact bodies in equilibrium. It should be remarked, however, that this book makes a rather strong selection of topics and concentrates fundamentally on presenting the main results obtained by the authors during their research in this field. The book starts with a chapter where the fundamental aspects of rotating fluids in equilibrium, including its thermodynamic properties, are summarized. Of particular interest are the so-called mass-shedding limit, which is the limit where the body is rotating so fast that it is on the verge of starting

  19. Characterization of post-translational modifications of histone H2B-variants isolated from Arabidopsis thaliana.

    PubMed

    Bergmüller, Eveline; Gehrig, Peter M; Gruissem, Wilhelm

    2007-09-01

    Eukaryotic DNA is structurally packed into chromatin by the basic histone proteins H2A, H2B, H3, and H4. There is increasing evidence that incorporation and post-translational modifications of histone variants have a fundamental role in gene regulation. While modifications of H3 and H4 histones are now well-established, considerably less is known about H2B modifications. Here, we present the first detailed characterization of H2B-variants isolated from the model plant Arabidopsis thaliana. We combined reversed-phase chromatography with tandem mass spectrometry to identify post-translational modifications of the H2B-variants HTB1, HTB2, HTB4, HTB9, and HTB11, isolated from total chromatin and euchromatin-enriched fractions. The HTB9-variant has acetylation sites at lysines 6, 11, 27, 32, 38, and 39, while Lys-145 can be ubiquitinated. Analogous modifications and an additional methylation of Lys-3 were identified for HTB11. HTB2 shows similar acetylation and ubiquitination sites and an additional methylation at Lys-11. Furthermore, the N-terminal alanine residues of HTB9 and HTB11 were found to be mono-, di-, or trimethylated or unmodified. No methylation of arginine residues was detected. The data suggest that most of these modification sites are only partially occupied. Our study significantly expands the map of covalent Arabidopsis histone modifications and is the first step to unraveling the histone code in higher plants. PMID:17691833

  20. Diagnosis and therapeutic management in a patient with type 2B-like acquired von Willebrand syndrome.

    PubMed

    Karger, Ralf; Weippert-Kretschmer, Monika; Budde, Ulrich; Kretschmer, Volker

    2011-03-01

    Acquired von Willebrand syndrome (AVWS) usually mimics von Willebrand disease (VWD) type 1 or 2A. However, in rare cases, the characteristics of other VWD types can predominate in AVWS that might require careful consideration of differential treatment options. The diagnosis and the treatment of a case of type 2B-like AVWS are discussed. Diagnosis of AVWS was ascertained by determining ristocetin cofactor activity, ristocetin-induced platelet aggregation, von Willebrand factor antigen, collagen binding and characterization of von Willebrand factor (VWF) multimers. Inhibitor presence was sought through mixing experiments, the Bethesda method, and calculation of the in-vivo recovery and plasma half-life of VWF after administration of factor VIII/VWF concentrate. Mutations in the A1 domain of VWF were ruled out by sequencing of exon 28 of the VWF gene. A 34-year-old male patient, putatively diagnosed with type 2B VWD, and undergoing laparoscopic cholecystectomy, did not respond adequately to perioperative hemostatic treatment with desmopressin and high doses of factor VIII/VWF concentrate, requiring the administration of recombinant activated factor VII. Further diagnostic workup revealed AVWS mimicking type 2B VWD, most likely owing to an autoantibody developed in the course of underlying monoclonal gammopathy of undetermined significance. The presence of AVWS should be considered before a diagnosis of type 2B VWD is made, especially in patients with a history atypical for inherited disease. PMID:21178586

  1. Trypanosoma brucei Co-opts NK Cells to Kill Splenic B2 B Cells

    PubMed Central

    Frenkel, Deborah; Guirnalda, Patrick; Haynes, Carole; Bockstal, Viki; Magez, Stefan; Black, Samuel J.

    2016-01-01

    After infection with T. brucei AnTat 1.1, C57BL/6 mice lost splenic B2 B cells and lymphoid follicles, developed poor parasite-specific antibody responses, lost weight, became anemic and died with fulminating parasitemia within 35 days. In contrast, infected C57BL/6 mice lacking the cytotoxic granule pore-forming protein perforin (Prf1-/-) retained splenic B2 B cells and lymphoid follicles, developed high-titer antibody responses against many trypanosome polypeptides, rapidly suppressed parasitemia and did not develop anemia or lose weight for at least 60 days. Several lines of evidence show that T. brucei infection-induced splenic B cell depletion results from natural killer (NK) cell-mediated cytotoxicity: i) B2 B cells were depleted from the spleens of infected intact, T cell deficient (TCR-/-) and FcγRIIIa deficient (CD16-/-) C57BL/6 mice excluding a requirement for T cells, NKT cell, or antibody-dependent cell-mediated cytotoxicity; ii) administration of NK1.1 specific IgG2a (mAb PK136) but not irrelevant IgG2a (myeloma M9144) prevented infection-induced B cell depletion consistent with a requirement for NK cells; iii) splenic NK cells but not T cells or NKT cells degranulated in infected C57BL/6 mice co-incident with B cell depletion evidenced by increased surface expression of CD107a; iv) purified NK cells from naïve C57BL/6 mice killed purified splenic B cells from T. brucei infected but not uninfected mice in vitro indicating acquisition of an NK cell activating phenotype by the post-infection B cells; v) adoptively transferred C57BL/6 NK cells prevented infection-induced B cell population growth in infected Prf1-/- mice consistent with in vivo B cell killing; vi) degranulated NK cells in infected mice had altered gene and differentiation antigen expression and lost cytotoxic activity consistent with functional exhaustion, but increased in number as infection progressed indicating continued generation. We conclude that NK cells in T. brucei infected mice

  2. Postsynaptic density protein 95-regulated NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in levodopa-induced dyskinesia rat models

    PubMed Central

    Ba, Maowen; Kong, Min; Ma, Guozhao

    2015-01-01

    Context Abnormality in interactions between N-methyl-d-aspartate (NMDA) receptor and its signaling molecules occurs in the lesioned striatum in Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID). It was reported that Fyn-mediated NR2B tyrosine phosphorylation, can enhance NMDA receptor function. Postsynaptic density protein 95 (PSD-95), one of the synapse-associated proteins, regulates interactions between receptor and downstream-signaling molecules. In light of the relationship between PSD-95, NR2B, and Fyn kinases, does PSD-95 contribute to the overactivity of NMDA receptor function induced by dopaminergic treatment? To further prove the possibility, the effects of regulating the PSD-95 expression on the augmented NR2B tyrosine phosphorylation and on the interactions of Fyn and NR2B in LID rat models were evaluated. Methods In the present study, parkinsonian rat models were established by injecting 6-hydroxydopamine. Subsequently, valid PD rats were treated with levodopa (50 mg/kg/day with benserazide 12.5 mg/kg/day, twice daily) intraperitoneally for 22 days to create LID rat models. Then, the effect of pretreatment with an intrastriatal injection of the PSD-95mRNA antisense oligonucleotides (PSD-95 ASO) on the rotational response to levodopa challenge was assessed. The effects of pretreatment with an intrastriatal injection of PSD-95 ASO on the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B in the LID rat models were detected by immunoblotting and immunoprecipitation. Results Levodopa administration twice daily for 22 days to parkinsonian rats shortened the rotational duration and increased the peak turning responses. The altered rotational responses were attenuated by PSD-95 ASO pretreatment. Meanwhile, PSD-95 ASO pretreatment decreased the level of PSD-95 protein expression and reduced both the augmented NR2B tyrosine phosphorylation and interactions of Fyn with NR2B triggered during the levodopa administration in the

  3. Copy Number Variation of UGT 2B Genes in Indian Families Using Whole Genome Scans

    PubMed Central

    Veerappa, Avinash M.; Padakannaya, Prakash; Ramachandra, Nallur B.

    2016-01-01

    Background and Objectives. Uridine diphospho-glucuronosyltransferase 2B (UGT2B) is a family of genes involved in metabolizing steroid hormones and several other xenobiotics. These UGT2B genes are highly polymorphic in nature and have distinct polymorphisms associated with specific regions around the globe. Copy number variations (CNVs) status of UGT2B17 in Indian population is not known and their disease associations have been inconclusive. It was therefore of interest to investigate the CNV profile of UGT2B genes. Methods. We investigated the presence of CNVs in UGT2B genes in 31 members from eight Indian families using Affymetrix Genome-Wide Human SNP Array 6.0 chip. Results. Our data revealed >50% of the study members carried CNVs in UGT2B genes, of which 76% showed deletion polymorphism. CNVs were observed more in UGT2B17 (76.4%) than in UGT2B15 (17.6%). Molecular network and pathway analysis found enrichment related to steroid metabolic process, carboxylesterase activity, and sequence specific DNA binding. Interpretation and Conclusion. We report the presence of UGT2B gene deletion and duplication polymorphisms in Indian families. Network analysis indicates the substitutive role of other possible genes in the UGT activity. The CNVs of UGT2B genes are very common in individuals indicating that the effect is neutral in causing any suspected diseases. PMID:27092269

  4. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED...

  5. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED...

  6. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED...

  7. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED...

  8. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10 to Part 223—Flounder TED...

  9. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  10. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  11. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  12. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Figures B Appendix B to Subpart D of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 89, Subpt. D, App. B Appendix B to Subpart D of Part 89—Figures EC01MR92.000 EC01MR92.001...

  13. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Figures B Appendix B to Subpart D of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 89, Subpt. D, App. B Appendix B to Subpart D of Part 89—Figures EC01MR92.000 EC01MR92.001...

  14. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Figures B Appendix B to Subpart D of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 90, Subpt. D, App. B Appendix B to Subpart D of Part 90—Figures EC01MR92.085 EC01MR92.086...

  15. 40 CFR Appendix B to Subpart E of... - Figures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Figures B Appendix B to Subpart E of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Procedures Pt. 90, Subpt. E, App. B Appendix B to Subpart E of Part 90—Figures EC01MR92.087...

  16. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Figures B Appendix B to Subpart D of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 90, Subpt. D, App. B Appendix B to Subpart D of Part 90—Figures EC01MR92.085 EC01MR92.086...

  17. 40 CFR Appendix B to Subpart E of... - Figures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Figures B Appendix B to Subpart E of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Procedures Pt. 90, Subpt. E, App. B Appendix B to Subpart E of Part 90—Figures EC01MR92.087...

  18. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Figures B Appendix B to Subpart D of Part 91 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED.... D, App. B Appendix B to Subpart D of Part 91—Figures ER04OC96.013 ER04OC96.014...

  19. Interpreting Children's Human Figure Drawings: Basic Guidelines for School Counselors

    ERIC Educational Resources Information Center

    Foley, Yuehong Chen; Mullis, Fran

    2008-01-01

    The literature was reviewed and summarized to provide common interpretations of human figure drawings. Basic guidelines for interpreting human figure drawings (i.e., face and head, body, arms and hands, and legs and feet) are presented. Expectations for students at different developmental levels (ages 1 1/2 through adolescence) are identified, and…

  20. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  1. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  2. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  3. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  4. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  5. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  6. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  7. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  8. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  9. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  10. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  11. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  12. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  13. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 2 Figure 2 to Part...

  14. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  15. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  16. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  17. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  18. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  19. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  20. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  1. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 2 Figure 2 to Part...

  2. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  3. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  4. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  5. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  6. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 2 Figure 2 to Part...

  7. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  8. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  9. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  10. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  11. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 2 Figure 2 to Part...

  12. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  13. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  14. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  15. 16 CFR Figure 2 to Part 1509 - Headform Probe

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Headform Probe 2 Figure 2 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 2 Figure 2 to Part 1509—Headform Probe EC03OC91.065...

  16. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  17. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  18. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  19. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  20. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  1. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  2. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  3. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  4. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  5. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  6. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  7. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  8. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  9. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  10. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform Probe EC03OC91.062...

  11. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  12. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  13. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  14. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  15. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  16. 16 CFR Figure 2 to Part 1509 - Headform Probe

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Headform Probe 2 Figure 2 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 2 Figure 2 to Part 1509—Headform Probe EC03OC91.065...

  17. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  18. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  19. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  20. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  1. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  2. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  3. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  4. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform Probe EC03OC91.062...

  5. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  6. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  7. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  8. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  9. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  10. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  11. Distinguishing between Realistic and Fantastical Figures in Iran

    ERIC Educational Resources Information Center

    Davoodi, Telli; Corriveau, Kathleen H.; Harris, Paul L.

    2016-01-01

    Children in the United States come to distinguish historical from fictional story figures between the ages of 3 and 5 years, guided by the plausibility of the story events surrounding the figure (Corriveau, Kim, Schwalen, & Harris, 2009; Woolley & Cox, 2007). However, U.S. children vary in their reactions to stories that include…

  12. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  13. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  14. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  15. 50 CFR Figure 22 to Part 679 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 11 2011-10-01 2011-10-01 false 22 Figure 22 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE ECONOMIC ZONE OFF ALASKA Figure 22 to Part 679...

  16. 50 CFR Figure 11 to Part 223 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false 11 Figure 11 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figure 11 to Part 223...

  17. 50 CFR Figure 22 to Part 679 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 13 2014-10-01 2014-10-01 false 22 Figure 22 to Part 679 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE (CONTINUED) FISHERIES OF THE EXCLUSIVE ECONOMIC ZONE OFF ALASKA Figure 22 to Part 679...

  18. 50 CFR Figure 11 to Part 223 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false 11 Figure 11 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figure 11 to Part 223...

  19. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  20. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...